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Sample records for comparative biodistribution study

  1. In vivo studies: comparing the administration via and the impact on the biodistribution of radiopharmaceuticals

    International Nuclear Information System (INIS)

    Pinto, Suyene Rocha; Sarcinelle, Michelle Alvares; Souza Albernaz, Marta de; Silva, Franciana Maria Rosa da; Seabra, Sergio Henrique; Almeida do Nascimento, Patricia; Carvalho, Cosme Leonardo Gomes; Santos-Oliveira, Ralph

    2014-01-01

    The use of in vivo assay to determine the biodistribution and subsequent inter-comparison with human parameters has been used since the dawn of science. The use of this type of test admits the metabolic equity among animals for inter-comparison. Thus, the use of Wistar rats in particular is quite frequent. Regarding routes of administration, there are three ways to test priority: jugular vein, intraocular (eye plexus) and caudal; there is a consensus that these three pathways behave in the same way, or at least very similar. Biodistribution studies of drugs, especially radiopharmaceuticals, have been using randomly any of these pathways believed to be effective in their likeness without worrying about your real analytic equity. In this study, we performed in vivo assay in 8 Wistar rats using 99mTc -labeled Herceptin to review the route of administration on the biodistribution result. Thus, four mice were injected via the intraocular (eye plexus), and four were injected via tail (caudal plexus). The results were quite disparate and call the attention of the scientific community to reassess the protocols for animal experiments, in order to have uniformity and fairness between the data and may represent a test for human inter-comparison of more reliable and trustworthy way

  2. Comparative study of two different Bombesin derivates labeled with 111In and biodistribution in normal mice

    International Nuclear Information System (INIS)

    Oliveira, Ricardo S.; Alcarde, Lais F.; Correa, Beatriz L.; Massicano, Adriana V.F.; Couto, Renata M.; Mengatti, Jair; Araujo, Elaine B. de

    2013-01-01

    Nuclear medicine is a medical speciality that uses radioactive compounds (radiopharmaceuticals), consisting of a substrate and a radioactive isotope, for diagnostic. Among the peptides of interest for Nuclear Medicine, bombesin (BBN), a 14 amino acid neuropeptide analog of human gastrin-releasing peptide, is one of the highlights. This is a comparative study aiming to establish the best condition to radiolabel two BBN derivatives, (DTPA-Phe-Gly 5 -BBN (6-14) ) and (DTPA-Phe-Gly 2 -BBN (6-14 )) with 111-indium. Specific objectives of this study were evaluate a good condition of radiolabelling in search excellent specific activity the bombesin derivatives and determinate the biodistribution in health mice model. Ten micrograms (10μg) of the derivative DTPA-Phe-Gly2-BBN (6-14) was labeled with 18.5 MBq (0.5 mCi) of 111 InCl 3 at 25°C for different times (5, 15 and 30 minutes). The best condition was applied to peptide mass variation (10, 5, 2.5, 1, 0.5, 0.25 and 0.1 μg), keeping all other parameters fixed. Finally, the influence of 111 InCl 3 activity in the radiolabeling process (18.5, 37, 55.5, 74, 185 MBq) was evaluated. The best conditions were repeated for the second derivate, DTPA-Phe-Gly 5 -BBN (6-14 ). The radiochemical purity was assessed by thin layer chromatography (TLC), using 0.2 M EDTA pH 5 as solvent, and high performance liquid chromatography (HPLC) with a C18 column with linear gradient 10% A to 90% A (v/v) (A: 0,1% of TFA in CH3CN; B: 0,1% of TFA in H2O) at a flow rate of 1 mL/minute for 15 minutes. Considering the reaction time, the higher radiochemical purity was obtained when 10μg of the peptide was labeled with 18.5 MBq (0.5 mCi) of 111 In for 15 minutes at 25°C (97.33 ± 0.50%, n=3). In the mass variation study, the best results of radiochemical purity were obtained when 10 μg of the peptide was employed (97.69 ± 0.4%, n = 4). Finally, the maximum specific activity of the radiolabelled peptides was 1.85 MBq/ μg. The maximum specific

  3. Comparative study on biodistribution of domestic and imported 125I-β-CIT

    International Nuclear Information System (INIS)

    Liu Xingdang; Lin Xiangtong; Fang Ping; Chen Zhengping; Zhou Xiang; Wang Bocheng; Zhang Manda

    2003-01-01

    Objective: To characterize the kinetics and biodistribution of a domestically synthesized 125 I-2β-carbomethoxy-3β-4-iodopheny1tropane (β-CIT ) and to compare it with that of 125 I-β-CIT imported from RBI company. Methods: 1)The biodistribution of domestic and RBI company produced 125 I-β-CIT in KM mice. Twenty groups of mice (group of 5) were injected into the tail vein with either one of 125 I-β-CIT products. Each group of both products was killed at 5,15,30 and 45 min, and 1, 2, 4, 6, 8 and 24 h. 2)Autoradiography was performed on the brain of SD rats at 2 h after injection. Results: Domestic 125 I-β-CIT was primarily uptaked in the striatum, also in areas rich in 5-HTT such as the brain stem, frontal cortex, parietal cortex, temporal cortex, occipital cortex and hippocampus. Striatal uptake peaked at 2 h postinjection of 125 I-β-CIT. The ratio of specific to nonspecific binding in striatum peaked at 6 h. The highest radioactivity was in the lungs and the less radioactivity was in the liver, kidney, spleen and intestine. Autoradiography confirmed that 125 I-β-CIT primarily bound to striatum and lower room temperature significantly reduced the binding of the agent. Conclusion: The domestic 125 I-β-CIT binds primarily to dopamine transporters in the striatum in mice and rats and the maximum uptake is in the lungs

  4. Toxicology and Biodistribution: The Clinical Value of Animal Biodistribution Studies

    Directory of Open Access Journals (Sweden)

    Beatriz Silva Lima

    2018-03-01

    Full Text Available Since the human genome decoding, understanding and identification of genetic disturbances behind many diseases, including cancer, are intensively increasing. Scientific and technological advances in this area trigger the search for therapeutic (curative approaches targeting the correction of gene disturbances. Gene therapy medicinal products (GTMPs emerge in this context, bringing new challenges for their characterization. Compared to small molecules, biodistribution is fundamental to identifying target organs and anticipating safety and efficacy, may be integrated into safety and pharmacology studies, and may eventually be anticipated based on specificities of vectors and constructs. This review describes and discusses the requirements for nonclinical development and evaluation of GTMPs versus conventional ones and the needs and challenges of constructing nonclinical packages that assure GTMPs’ human safety from early development, taking into consideration usefulness and/or limitations of many conventional, preclinical models. The experience gained in the European context is referenced.

  5. Comparative study of two different Bombesin derivates labeled with {sup 111}In and biodistribution in normal mice

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Ricardo S.; Alcarde, Lais F.; Correa, Beatriz L.; Massicano, Adriana V.F.; Couto, Renata M.; Mengatti, Jair; Araujo, Elaine B. de, E-mail: ricardooliveira@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Nuclear medicine is a medical speciality that uses radioactive compounds (radiopharmaceuticals), consisting of a substrate and a radioactive isotope, for diagnostic. Among the peptides of interest for Nuclear Medicine, bombesin (BBN), a 14 amino acid neuropeptide analog of human gastrin-releasing peptide, is one of the highlights. This is a comparative study aiming to establish the best condition to radiolabel two BBN derivatives, (DTPA-Phe-Gly{sub 5}-BBN{sub (6-14)}) and (DTPA-Phe-Gly{sub 2}-BBN{sub (6-14})) with 111-indium. Specific objectives of this study were evaluate a good condition of radiolabelling in search excellent specific activity the bombesin derivatives and determinate the biodistribution in health mice model. Ten micrograms (10μg) of the derivative DTPA-Phe-Gly2-BBN (6-14) was labeled with 18.5 MBq (0.5 mCi) of {sup 111}InCl{sub 3} at 25°C for different times (5, 15 and 30 minutes). The best condition was applied to peptide mass variation (10, 5, 2.5, 1, 0.5, 0.25 and 0.1 μg), keeping all other parameters fixed. Finally, the influence of {sup 111}InCl{sub 3} activity in the radiolabeling process (18.5, 37, 55.5, 74, 185 MBq) was evaluated. The best conditions were repeated for the second derivate, DTPA-Phe-Gly{sub 5}-BBN{sub (6-14}). The radiochemical purity was assessed by thin layer chromatography (TLC), using 0.2 M EDTA pH 5 as solvent, and high performance liquid chromatography (HPLC) with a C18 column with linear gradient 10% A to 90% A (v/v) (A: 0,1% of TFA in CH3CN; B: 0,1% of TFA in H2O) at a flow rate of 1 mL/minute for 15 minutes. Considering the reaction time, the higher radiochemical purity was obtained when 10μg of the peptide was labeled with 18.5 MBq (0.5 mCi) of {sup 111}In for 15 minutes at 25°C (97.33 ± 0.50%, n=3). In the mass variation study, the best results of radiochemical purity were obtained when 10 μg of the peptide was employed (97.69 ± 0.4%, n = 4). Finally, the maximum specific activity of the radiolabelled

  6. Studies on the biodistribution of dextrin nanoparticles

    International Nuclear Information System (INIS)

    Goncalves, C; Gama, F M; Ferreira, M F M; Martins, J A; Santos, A C; Prata, M I M; Geraldes, C F G C

    2010-01-01

    The characterization of biodistribution is a central requirement in the development of biomedical applications based on the use of nanoparticles, in particular for controlled drug delivery. The blood circulation time, organ biodistribution and rate of excretion must be well characterized in the process of product development. In this work, the biodistribution of recently developed self-assembled dextrin nanoparticles is addressed. Functionalization of the dextrin nanoparticles with a DOTA-monoamide-type metal chelator, via click chemistry, is described. The metal chelator functionalized nanoparticles were labelled with a γ-emitting 153 Sm 3+ radioisotope and the blood clearance rate and organ biodistribution of the nanoparticles were obtained. The effect of PEG surface coating on the blood clearance rate and organ biodistribution of the nanoparticles was also studied.

  7. Studies on the biodistribution of dextrin nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Goncalves, C; Gama, F M [IBB-Institute for Biotechnology and Bioengineering, Centre for Biological Engineering, Minho University, Campus de Gualtar, 4710-057 Braga (Portugal); Ferreira, M F M; Martins, J A [Departamento de Quimica, Universidade do Minho, Campus de Gualtar, 4710-057 Braga (Portugal); Santos, A C; Prata, M I M [IBILI, Faculty of Medicine of the University of Coimbra, Coimbra (Portugal); Geraldes, C F G C, E-mail: fmgama@deb.uminho.pt [Departamento de Ciencias da Vida, Faculdade de Ciencia e Tecnologia e Centro de Neurociencias e Biologia Celular, Universidade de Coimbra (Portugal)

    2010-07-23

    The characterization of biodistribution is a central requirement in the development of biomedical applications based on the use of nanoparticles, in particular for controlled drug delivery. The blood circulation time, organ biodistribution and rate of excretion must be well characterized in the process of product development. In this work, the biodistribution of recently developed self-assembled dextrin nanoparticles is addressed. Functionalization of the dextrin nanoparticles with a DOTA-monoamide-type metal chelator, via click chemistry, is described. The metal chelator functionalized nanoparticles were labelled with a {gamma}-emitting {sup 153}Sm{sup 3+} radioisotope and the blood clearance rate and organ biodistribution of the nanoparticles were obtained. The effect of PEG surface coating on the blood clearance rate and organ biodistribution of the nanoparticles was also studied.

  8. Comparative pharmacokinetics and biodistribution studies of {sup 99m}Tc-annexin V produced by different radiolabeling methods

    Energy Technology Data Exchange (ETDEWEB)

    Santos, Josefina da Silva; Pujatti, Priscilla Brunelli; Couto, Renata Martinussi; Mengatti, Jair; Araujo, Elaine Bortoleti de, E-mail: jssantos@usp.b, E-mail: priscillapujatti@yahoo.com.b, E-mail: renatamartinussicouto@yahoo.com.b, E-mail: jmengatti@ipen.b, E-mail: ebaraujo@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2009-07-01

    The use of radiolabeled annexin A5 (ANXA5) to detect cell death in vivo has increased in the last years. Several {sup 99m}Tc-labeling techniques were reported using different cores, such as [{sup 99m}Tc=O]{sup +3}, [{sup 99m}Tc]HYNIC, [{sup 99m}Tcident toN]{sup +2} and [Tc(CO{sub 3})]{sup +1}. The goal of the present work was to evaluate the influence of {sup 99m}Tc cores in the biological behavior of radiolabeled ANXA5 in Swiss mice using [{sup 99m}Tc=O]{sup +3}, [{sup 99m}Tc]HYNIC cores. Ethylenedicysteine (EC) was applied to obtain [Tc=O]{sup +3} core, N,N,N',N'-tetramethyl(succinimide) uranium tetrafluoroborate (TSTU) was employed to transfer the carboxyl group to their corresponding hydroxysuccinimide ester and HYNIC-ANXA5 was provided by National Cancer Institute-Frederick. ITLC-SG and HPLC analysis were applied to determine non-desirable products and the stability of preparations was evaluated after incubation at room temperature, 4 deg C and in human serum at 37 deg C. In vivo biodistribution and kinetics studies were performed after the intravenous injection of {sup 99m}Tc-HYNIC-ANXA5 and {sup 99m}Tc-EC-ANXA5 and pharmacokinetic parameters were calculated using Biexp software. ANXA5 was radiolabeled at room temperature with high yield (> 95%). The results of biodistribution in mice showed, as expected, higher renal uptake of {sup 99m}Tc-HYNICANXA5 and higher liver uptake of {sup 99m}Tc-EC-ANXA5. The percent injected activity per gram (% IA/g) in liver at 0.5 hours were 6.52 and 1.09 and in kidneys were 1.59 and 32.2 for {sup 99m}Tc-EC-ANXA5 and {sup 99m}Tc-HYNICANXA5, respectively. The results of radioactivity in blood showed that both HYNIC- and EC- radiolabeled ANXA5 presented fast blood clearance. In this study two {sup 99m}Tc-ANXA5 obtained from three different available radiolabeling methods presently were investigated. Each labeling method possesses unique advantages and disadvantages. (author)

  9. Comparative pharmacokinetics and biodistribution studies of 99mTc-annexin V produced by different radiolabeling methods

    International Nuclear Information System (INIS)

    Santos, Josefina da Silva; Pujatti, Priscilla Brunelli; Couto, Renata Martinussi; Mengatti, Jair; Araujo, Elaine Bortoleti de

    2009-01-01

    The use of radiolabeled annexin A5 (ANXA5) to detect cell death in vivo has increased in the last years. Several 99m Tc-labeling techniques were reported using different cores, such as [ 99m Tc=O] +3 , [ 99m Tc]HYNIC, [ 99m Tc≡N] +2 and [Tc(CO 3 )] +1 . The goal of the present work was to evaluate the influence of 99m Tc cores in the biological behavior of radiolabeled ANXA5 in Swiss mice using [ 99m Tc=O] +3 , [ 99m Tc]HYNIC cores. Ethylenedicysteine (EC) was applied to obtain [Tc=O] +3 core, N,N,N',N'-tetramethyl(succinimide) uranium tetrafluoroborate (TSTU) was employed to transfer the carboxyl group to their corresponding hydroxysuccinimide ester and HYNIC-ANXA5 was provided by National Cancer Institute-Frederick. ITLC-SG and HPLC analysis were applied to determine non-desirable products and the stability of preparations was evaluated after incubation at room temperature, 4 deg C and in human serum at 37 deg C. In vivo biodistribution and kinetics studies were performed after the intravenous injection of 99m Tc-HYNIC-ANXA5 and 99m Tc-EC-ANXA5 and pharmacokinetic parameters were calculated using Biexp software. ANXA5 was radiolabeled at room temperature with high yield (> 95%). The results of biodistribution in mice showed, as expected, higher renal uptake of 99m Tc-HYNICANXA5 and higher liver uptake of 99m Tc-EC-ANXA5. The percent injected activity per gram (% IA/g) in liver at 0.5 hours were 6.52 and 1.09 and in kidneys were 1.59 and 32.2 for 99m Tc-EC-ANXA5 and 99m Tc-HYNICANXA5, respectively. The results of radioactivity in blood showed that both HYNIC- and EC- radiolabeled ANXA5 presented fast blood clearance. In this study two 99m Tc-ANXA5 obtained from three different available radiolabeling methods presently were investigated. Each labeling method possesses unique advantages and disadvantages. (author)

  10. [Comparative study of the biodistribution of (99m)Tc-HYNIC-Lys3-Bombesin obtained with the EDDA/tricine and NA/tricine as coligands].

    Science.gov (United States)

    Hernández-Cairo, A; Perera-Pintado, A; Prats-Capote, A; Batista-Cuellar, J F; Casacó-Santana, C

    2012-01-01

    The aim of present investigation was to evaluate biodistribution in healthy animals and in tumor models of the radiopharmaceuticals (99m)Tc-EDDA/tricine-HYNIC-Lys3-Bombesin (HYNIC-Lys3-BN) and (99m)Tc-NA/tricine-HYNIC-Lys3-BN. Biodistribution and pharmacokinetics were carried out over 24 hours. To do so, 24 healthy Wistar rats were used and were administered 37.0 ± 0.8 MBq/rat of each radiopharmaceutical. For the tumor model study, 20 CD-1 nude mice were used and prostate tumors (PC3) were implanted in all the mice. Ten days later, tumor volumes were calculated and 40.00 ± 0.04 MBq/mice of each radiopharmaceutical were injected. Both showed high radiochemical purity: 98.08 ± 0.25% for EDDA/tricine product and 95.1 ± 0.3% for the conjugate with NA/tricine. Uptake of the radiopharmaceutical with NA/tricine was significantly higher in organs of the reticulo-endothelial system of healthy Wistar rats during 24h, specifically in the liver and spleen. Both labeled compounds showed no significant differences between their blood elimination half lives. Average of tumor growth was 0.93 ± 0.02 cm(3) and affinity for tumors showed a growing and specific binding of both radiopharmaceuticals, although it was significantly higher for the EDDA/tricine conjugate. This outcome made it possible to corroborate the direct relationship between the density of gastrin releasing peptide and its receptors (GRPr) and the variation of the accumulation of the radiopharmaceuticals in the tumor. Use of EDDA/tricine as coligand is more appropriate than NA/tricine for labeling of HYNIC-Lys3-BN with (99m)Tc. Copyright © 2011 Elsevier España, S.L. y SEMNIM. All rights reserved.

  11. Stealth lipid polymer hybrid nanoparticles loaded with rutin for effective brain delivery - comparative study with the gold standard (Tween 80): optimization, characterization and biodistribution.

    Science.gov (United States)

    Ishak, Rania A H; Mostafa, Nada M; Kamel, Amany O

    2017-11-01

    The blood-brain barrier is considered the leading physiological obstacle hindering the transport of neurotherapeutics to brain cells. The application of nanotechnology coupled with surfactant coating is one of the efficacious tactics overcoming this barrier. The aim of this study was to develop lipid polymer hybrid nanoparticles (LPHNPs), composed of a polymeric core and a phospholipid shell entangled, for the first time, with PEG-based surfactants (SAA) viz. TPGS or Solutol HS 15 in comparison with the gold standard Tween 80, aiming to enhance brain delivery and escape opsonization. LPHNPs were successfully prepared using modified single-step nanoprecipitation technique, loaded with the flavonoid rutin (RU), extracted from the flowers of Calendula officinalis L., and recently proved as a promising anti-Alzheimer. The effect of the critical process parameters (CPP) viz. PLGA amount, W lecithin /W PLGA ratio, and Tween 80 concentration on critical quality attributes (CQA); entrapment, size and size distribution, was statistically analyzed via design of experiments, and optimized using the desirability function. The optimized CPP were maintained while substituting Tween 80 with other PEG-SAA. All hybrid particles exhibited spherical shape with perceptible lipid shells. The biocompatibility of the prepared NPs was confirmed by hemolysis test. The pharmacokinetic assessments, post-intravenous administration to rats, revealed a significant higher RU bioavailability for NPs relative to drug solution. Biodistribution studies proved non-significant differences in RU accumulation within brain, but altered phagocytic uptake among various LPHNPs. The present study endorses the successful development of LPHNPs using PEG-SAA, and confirms the prospective applicability of TPGS and Solutol in enhancing brain delivery.

  12. Dosimetry implications of BSH biodistribution study at OSU

    International Nuclear Information System (INIS)

    Gupta, N.; Albertson, B.J.; Gahbauer, R.A.; Barth, R.F.; Goodman, J.H.

    2000-01-01

    A BSH biodistribution study was performed at Ohio State University, where tumor, normal brain, and blood boron concentrations of patients undergoing tumor debulking surgery were acquired. The results of this biodistribution study are subjects of other presentations in this meeting. In this paper, we present an overview of the dosimetry implications of this biodistribution data. The analysis for this paper assumed that the tumor boron RBE was factor of two higher than the normal brain boron RBE. Our conclusions from this analysis were that with the tumor/blood ratios observed in our patients for times of up to 14 hours post commencement of boron infusion, one could not successfully treat patients with BNCT using BSH. (author)

  13. Single dose toxicity and biodistribution studies of [18F] fluorocholine

    International Nuclear Information System (INIS)

    Campos, Danielle C.; Santos, Priscilla F.; Silveira, Marina B.; Ferreira, Soraya Z.; Malamut, Carlos; Silva, Juliana B. da; Souza, Cristina M.; Campos, Liliane C.; Ferreira, Enio; Araujo, Marina R.; Cassali, Geovanni D.

    2013-01-01

    [ 18 F]Fluorocholine ( 18 FCH) is a valuable tool for non-invasive diagnosis using positron emission tomography (PET). This radiotracer has been proven to be highly effective in detecting recurrences and staging prostate cancer, diagnoses brain, breast, and esophageal tumors and also hepatocellular carcinoma. The higher uptake of fluorocholine by malignant tumors results from increased choline kinase activity due to accelerated cell multiplication and membrane formation. According to the Brazilian Health Surveillance Agency (ANVISA), radiopharmaceuticals have to be registered before commercialization. The aim of this work was to evaluate single dose toxicity and biodistribution of 18 FCH in mice, since preclinical safety studies are required for register. Experimental procedures were approved by the Ethics Committee on Animal Use (CEUA-IPEN/SP). Single dose toxicity and biodistribution studies were conducted in Swiss mice. No signs of toxicity were observed during clinical trial. No changes in the parameters which were examined, such as: body weight, food consumption, clinical pathology parameters or lesions microscopic were noted. Biodistribution results indicated high physiological tracer uptake in kidney, liver and heart 30 min after injection. Lower activities were recorded in other organs/tissues: pancreas, intestine, spleen, bone, bladder, muscle, brain and blood. Initial preclinical investigations showed no toxic effects of 18 FCH at investigated doses and a biodistribution profile very similar to other reports in literature. This information is essential to support future human trials. (author)

  14. Nanobarcoding for improved nanoparticle detection in nanomedical biodistribution studies

    Science.gov (United States)

    Eustaquio, Trisha

    Determination of the fate of nanoparticles (NPs) in a biological system, or NP biodistribution, is critical in evaluating a NP formulation for nanomedicine. Unlike small-molecule drugs, NPs impose unique challenges in the design of appropriate biodistribution studies due to their small size and subsequent detection signal. Current methods to determine NP biodistribution are greatly inadequate due to their limited detection thresholds. There is an overwhelming need for a sensitive and efficient imaging-based method that can (1) detect and measure small numbers of NPs of various types, ideally single NPs, (2) associate preferential NP uptake with histological cell type by preserving spatial information in samples, and (3) allow for relatively quick and accurate NP detection in in vitro (and possibly ex vivo) samples for comprehensive NP biodistribution studies. Herein, a novel method for improved NP detection is proposed, coined "nanobarcoding." Nanobarcoding utilizes a non-endogenous oligonucleotide, or "nanobarcode" (NB), conjugated to the NP surface to amplify the detection signal from a single NP via in situ polymerase chain reaction (ISPCR), and this signal amplification will facilitate rapid and precise detection of single NPs inside cells over large areas of sample such that more sophisticated studies can be performed on the NP-positive subpopulation. Moreover, nanobarcoding has the potential to be applied to the detection of more than one NP type to study the effects of physicochemical properties, targeting mechanisms, and route of entry on NP biodistribution. The nanobarcoding method was validated in vitro using NB-functionalized superparamagnetic iron oxide NPs (NB-SPIONs) as the model NP type for improved NP detection inside HeLa human cervical cancer cells, a cell line commonly used for ISPCR-mediated detection of human papilloma virus (HPV). Nanotoxicity effects of NB-SPIONs were also evaluated at the single-cell level using LEAP (Laser-Enabled Analysis

  15. Detection of sites of infection in mice using 99mTc-labeled PN2S-PEG conjugated to UBI and 99mTc-UBI: a comparative biodistribution study

    International Nuclear Information System (INIS)

    Melendez-Alafort, Laura; Nadali, Anna; Pasut, Gianfranco; Zangoni, Elena; De Caro, Raffaele; Cariolato, Luca; Giron, Maria Cecilia; Castagliuolo, Ignazio; Veronese, Francesco M.; Mazzi, Ulderico

    2009-01-01

    The antimicrobial peptide ubiquicidin (UBI) directly labeled with technetium-99m ( 99m Tc) has recently been shown to be specifically taken up at sites of infection; however, its chemical structure is not well defined. To address this problem, the aim of the present study was to label UBI using poly(ethyleneglycol)-N-(N-(3-diphenylphosphinopropionyl)glycyl) -S-tritylcysteine ligand (PEG-PN 2 S) in order to compare its ability to detect infection sites with that of 99m Tc-UBI. Methods: The PN 2 S-PEG-UBI conjugate was prepared and labeled with 99m Tc, and its radiochemical purity was subsequently assessed. The stability of the conjugate to cysteine challenge and dilution with both saline solution and phosphate buffer was determined and serum stability and protein binding were also assessed. In vivo studies were carried out in healthy mice to study the biodistribution of 99m Tc-PN 2 S-PEG-UBI and its precursor 99m Tc-PN 2 S-PEG and in infected mice to compare the uptakes of 99m Tc-UBI and 99m Tc-PN 2 S-PEG-UBI at the site of infection using scintigraphic imaging and ex vivo tissue counting. Results: 99m Tc-PN 2 S-PEG-UBI was obtained with high radiochemical purity (98±1%) and high stability. The amphiphilic nature of the conjugate leads to a tendency to form micellar aggregates that explain the high protein binding values obtained. Biodistribution studies in mice showed low renal clearance followed by a predominant reticuloendothelial system clearance that limits its application in the abdominal area. Statistical analysis revealed no significant difference between 99m Tc-UBI and 99m Tc-PN 2 S-PEG-UBI uptake in infected mouse thigh, and the site of infection was clearly visualized using scintigraphic imaging. Conclusions: 99m Tc-PN 2 S-PEG-UBI proved to be as effective as 99m Tc-UBI in detecting sites of infection; however, the well-defined chemical structure of 99m Tc-PN 2 S-PEG-UBI makes it a better candidate for clinical imaging of infection

  16. Detection of sites of infection in mice using {sup 99m}Tc-labeled PN{sub 2}S-PEG conjugated to UBI and {sup 99m}Tc-UBI: a comparative biodistribution study

    Energy Technology Data Exchange (ETDEWEB)

    Melendez-Alafort, Laura [Department of Pharmaceutical Sciences, University of Padua, 35131 Padova (Italy)], E-mail: lmalafort@yahoo.com; Nadali, Anna; Pasut, Gianfranco; Zangoni, Elena [Department of Pharmaceutical Sciences, University of Padua, 35131 Padova (Italy); De Caro, Raffaele [Department of Anatomy and Physiology, University of Padua, 35131 Padova (Italy); Cariolato, Luca [Department of Pharmaceutical Sciences, University of Padua, 35131 Padova (Italy); Giron, Maria Cecilia [Department of Pharmacology and Anesthesiology, University of Padua, 35131 Padova (Italy); Castagliuolo, Ignazio [Department of Histology, Microbiology and Medical Biotechnologies, University of Padua, 35131 Padova (Italy); Veronese, Francesco M.; Mazzi, Ulderico [Department of Pharmaceutical Sciences, University of Padua, 35131 Padova (Italy)

    2009-01-15

    The antimicrobial peptide ubiquicidin (UBI) directly labeled with technetium-99m ({sup 99m}Tc) has recently been shown to be specifically taken up at sites of infection; however, its chemical structure is not well defined. To address this problem, the aim of the present study was to label UBI using poly(ethyleneglycol)-N-(N-(3-diphenylphosphinopropionyl)glycyl) -S-tritylcysteine ligand (PEG-PN{sub 2}S) in order to compare its ability to detect infection sites with that of {sup 99m}Tc-UBI. Methods: The PN{sub 2}S-PEG-UBI conjugate was prepared and labeled with {sup 99m}Tc, and its radiochemical purity was subsequently assessed. The stability of the conjugate to cysteine challenge and dilution with both saline solution and phosphate buffer was determined and serum stability and protein binding were also assessed. In vivo studies were carried out in healthy mice to study the biodistribution of {sup 99m}Tc-PN{sub 2}S-PEG-UBI and its precursor {sup 99m}Tc-PN{sub 2}S-PEG and in infected mice to compare the uptakes of {sup 99m}Tc-UBI and {sup 99m}Tc-PN{sub 2}S-PEG-UBI at the site of infection using scintigraphic imaging and ex vivo tissue counting. Results: {sup 99m}Tc-PN{sub 2}S-PEG-UBI was obtained with high radiochemical purity (98{+-}1%) and high stability. The amphiphilic nature of the conjugate leads to a tendency to form micellar aggregates that explain the high protein binding values obtained. Biodistribution studies in mice showed low renal clearance followed by a predominant reticuloendothelial system clearance that limits its application in the abdominal area. Statistical analysis revealed no significant difference between {sup 99m}Tc-UBI and {sup 99m}Tc-PN{sub 2}S-PEG-UBI uptake in infected mouse thigh, and the site of infection was clearly visualized using scintigraphic imaging. Conclusions: {sup 99m}Tc-PN{sub 2}S-PEG-UBI proved to be as effective as {sup 99m}Tc-UBI in detecting sites of infection; however, the well-defined chemical structure of {sup 99m

  17. Preparation and biodistribution study of 99Tcm labelled dextran conjugates

    International Nuclear Information System (INIS)

    Yang Chunhui; Li Hongyu; Liang Jixin; Lu Jia; Luo Hongyi; Zheng Deqiang; Sun Guiquan

    2012-01-01

    99 Tc m Mannosylated dextran conjugates were prepared through [ 99 Tc m (CO) 3 ] + precursor synthesized by carbonyl Isolink kit. The labelled conjugates were injected sub-dermally into the rear foots of the mice, and the patent blue solution was injected at the same site 10 min before sacrifice. The mice were killed at 1 h and 4 h postinjection, and the samples of different tissues including SLN, 2LN, injection site, liver, spleen, blood were dissected and counted. The uptake in terms was calculated. The results of biodistribution demonstrated that the SLN uptakes of radiopharmaceutical (without mannose in the molecules) were rather low and in vivo excretion of these conjugates were comparatively faster, and the uptake of injection site was also low; on the other hand, the SLN uptakes of radio pharmaceutical (with mannose in their molecules) were much higher than those of their corresponding dextran conjugates without mannose, but the retention in the injection site of these conjugates increased too. The results indicated that the affinity of mannosyl-dextran conjugates to the receptors on the surface of macrophages in the lymph node. In addition, the different relative molecular mass of dextran conjugates also cause different biodistribution results, the major one had higher SLN uptake, the difference was significant (P 99 Tc m (CO) 3 ] + labelled mannosylated dextran conjugates showed promising properties as SLN imaging agent and worth further investigation. (authors)

  18. A Phase 1 biodistribution study of p-boronophenylalanine

    International Nuclear Information System (INIS)

    Coderre, J.A.

    1991-01-01

    The objectives of the Phase I BPA biodistribution study are as follows: Objective 1: To establish the safety of orally administered boronophenylalanine (BPA) as determined by monitoring of patient's vital signs and by clinical analysis of blood before and after BPA administration. Objective 2: To establish BPA pharmacokinetics by monitoring the rates of boron absorption into and clearance from the blood and the rate of urinary excretion of boron. Objective 3: To measure the amount of boron incorporated into human tumors (melanoma, glioma, and breast carcinoma) using samples obtained at surgery or biopsy. This report presents the results obtained from the first thirteen patients entered into the study. Three additional glioblastoma patients have been studied recently at Stony Brook, the tissues are still being analyzed

  19. Labeling of vasoactive intestinal peptide (VIP) and VIP 10-28 fragment with radioiodine by direct method. Comparative study of the kinetics biodistribution and affinity for neuroendocrine tumor cells

    International Nuclear Information System (INIS)

    Colturato, Maria Tereza

    2005-01-01

    mixture (simple purification) and to produce the radiopharmaceutical with high specific activity (complex purification and HPLC), were both efficient in the separation of the species in the reaction mixtures, as demonstrated by quality control procedures. Biological distribution studies were accomplished by venous administration of the radiopharmaceuticals in laboratory animals: biodistribution study of [ 131 I]VIP and [ 131 I]VIP 10-28 in normal Swiss mice, [ 131 I]VIP not purified and purified in Swiss mice with tumor and [ 131 I]VIP and [ 131 I]VIP 10-28 in Nude mice with tumor, scintigraphic images of [ 131/123 I]VIP and [ 123 I]VIP 10-28 in Swiss and Nude mice and Wistar rats with tumor. In vitro studies were accomplished to determine the percentage of [ 131 I]VIP and [ 131 I]VIP 10-28 bound to plasmatic proteins, stability study of [ 131 I]VIP and [ 131 I]VIP 10-28 in human plasma and the affinity and internalization of [ 131 I]VIP and [ 131 I]VIP 10-28 by tumour adenocarcinoma cells of human rectal colon (HT-29). All biological distribution studies demonstrated that both [ 131/123 I]VIP and [ 131/123 I]VIP 10-28 showed fast blood clearance, low renal and liver uptake, relative uptake in thyroid, showing in vivo dehalogenation and good uptake in tumour. Comparative biological distribution of the radiopharmaceuticals showed high uptake in the stomach for both peptides. The blood clearance of the fragment was slower, and influences the visualization of the tumour mass. The radiopharmaceuticals, [ 123 I]VIP and [ 123 I]VIP 10-28, were obtained with high radiochemical purity, but with low radiochemical yield when comparing with labeling procedures using iodine-131. Quality control assays of [ 123 I]Na indicated that the presence of radiochemical and radionuclide impurities influenced on labeling results. (author)

  20. 125I-β-CIT biodistribution study in animals

    International Nuclear Information System (INIS)

    Hu Ping

    2000-01-01

    The purpose is to study the preparation and biodistribution in animal of dopamine transporter imaging agent 125 I-β-CIT. β-CIT was 125 I radioiodinated with Iodogen method, the dynamic distribution of 125 I-β-CIT in brain and critical organs were studied with SD rat (autoradiography) and NIH mice respectively. The radiolabelling yield of 125 I-β-CIT was 84%, the radiochemical purity was better than 98%. Blood clearance could be explained by two-compartment model with a duration of 12h, (α = 3.87, T 1/2α = 0.179, β = 0.162, T 1/2β = 4.276) and three-compartment model in 24 h, (Pi = 5.28, T 1/2Pi = 0.131, α = 0.403, T 1/2α = 1.719, β 0.040, T 1/2β = 17.298). The maxim uptake rate of brain (9.1% +- 1.0%) was reaches at 1h, while at 24h, the target/noise ratio was higher . Critical organs liver, lung, spleen and kidney had high uptake rate [(9.88 +- 1.43) - (16.29 +- 1.72)], except liver, other organs showed quick clearance (T 1/2 125 I-β-CIT has a high striatum uptake and good stability in vivo, can provide good SPECT images, the best acquisition time of SPECT may be about 20h after i.v

  1. Phase I biodistribution and pharmacokinetic study of Lewis Y targeting immunoconjugate CMD-193 in patients with advanced epithelial cancers

    International Nuclear Information System (INIS)

    Herbertson, R. A.; Lee, F. T.; Hopkins, W.; Smyth, F. E.; Murone, C.; Tebbutt, N. C.; Micallef, N.; MacFarlane, D. J.; Bellen, J.; Sonnichsen, D. S.; Brechbiel, M. W.; Scott, A. M.; Lee, T. L.

    2009-01-01

    Full text:Background: The Lewis Y (Ley) antigen is a blood-group related antigen expressed in >70% of solid tumours. This study explored the biodistribution and pharmacokinetics of the immunoconjugate CMD-193 (humanized anti-Ley antibody conjugated with calichaemicin) in patients with advanced Ley expressing epithelial cancers. Methods: There were 2 dose cohorts, (1.0mg/m2 and 2.6mg/m2). Primary objectives were to determine biodistribution and pharmacokinetics of CMD-193. The first cycle was labelled with 111In for biodistribution assessment, and subsequent cycles were administered 3 weekly to a maximum of 6 cycles. Tumour targeting was assessed using SPECT imaging, and pharmacokinetic analysis was based on gamma counting (111In-CMD-193) and ELISA (CMD-193 protein). Results: Nine patients were enrolled, and received 1-6 treatment cycles. Biodistribution imaging demonstrated initial blood pooling, followed by markedly increased hepatic uptake by day 2 (which persisted to day 8), and fast blood clearance. This pattern was seen for all patients, with no significant tumour uptake visualised in any patient. The overall T 1 /2 of 111In-CMD-193 complex formation in blood. One patient had partial metabolic response on 18F-FDG-PET. No radiologic responses were observed. Conclusions: CMD-193 demonstrates rapid blood clearance and increased hepatic uptake compared to prior studies of the original non-conjugated antibody. This trial highlights the importance of biodistribution and pharmacodynamic assessment in early phase studies of new biologics in clinical development.

  2. Comparative biodistribution of 12 {sup 111}In-labelled gastrin/CCK2 receptor-targeting peptides

    Energy Technology Data Exchange (ETDEWEB)

    Laverman, Peter; Joosten, Lieke; Eek, Annemarie; Roosenburg, Susan; Oyen, Wim J.G.; Boerman, Otto C. [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands); Peitl, Petra Kolenc [University Medical Centre Ljubljana, Department of Nuclear Medicine, Ljubljana (Slovenia); Maina, Theodosia [National Center for Scientific Research Demokritos, Molecular Radiopharmacy, Institute of Radioisotopes-Radiodiagnostic Products, Athens (Greece); Maecke, Helmut [University Hospital Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Aloj, Luigi [Fondazione ' ' G. Pascale' ' , Department of Nuclear Medicine, Istituto Nazionale Tumouri, Naples (Italy); Guggenberg, Elisabeth von [Innsbruck Medical University, Department of Nuclear Medicine, Innsbruck (Austria); Sosabowski, Jane K. [Queen Mary, University of London, Centre for Molecular Oncology and Imaging, Institute of Cancer, Barts and The London School of Medicine and Dentistry, London (United Kingdom); Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Reubi, Jean-Claude [University of Berne, Institute of Pathology, Berne (Switzerland)

    2011-08-15

    Cholecystokinin 2 (CCK-2) receptor overexpression has been demonstrated in various tumours such as medullary thyroid carcinomas and small-cell lung cancers. Due to this high expression, CCK-2 receptors might be suitable targets for radionuclide imaging and/or radionuclide therapy. Several CCK-2 receptor-binding radiopeptides have been developed and some have been tested in patients. Here we aimed to compare the in vivo tumour targeting properties of 12 {sup 111}In-labelled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-conjugated gastrin/CCK2 receptor-binding peptides. Two CCK8-based peptides and ten gastrin-based peptide analogues were tested. All peptides were conjugated with DOTA and labelled with {sup 111}In. Biodistribution studies were performed in mice with subcutaneous CCK2/gastrin receptor-expressing tumours and with receptor-negative tumours contralaterally. Biodistribution was studied by counting dissected tissues at 1 and 4 h after injection. Both the CCK analogues displayed relatively low tumour uptake (approximately 2.5%ID/g) as compared to minigastrin analogues. Two linear minigastrin peptides (MG0 and sargastrin) displayed moderate tumour uptake at both 1 and 4 h after injection, but also very high kidney uptake (both higher than 48%ID/g). The linear MG11, lacking the penta-Glu sequence, showed lower tumour uptake and also low kidney uptake. Varying the N-terminal Glu residues in the minigastrin analogues led to improved tumour targeting properties, with PP-F11 displaying the optimal biodistribution. Besides the monomeric linear peptides, a cyclized peptide and a divalent peptide were tested. Based on these studies, optimal peptides for peptide receptor radionuclide targeting of CCK2/gastrin receptor-expressing tumours were the linear minigastrin analogue with six D-Glu residues (PP-F11), the divalent analogue MGD5 and the cyclic peptide cyclo-MG1. These peptides combined high tumour uptake with low kidney retention, and may

  3. Compartmental analysis to predict biodistribution in radiopharmaceutical design studies

    Energy Technology Data Exchange (ETDEWEB)

    Lima, Marina F.; Pujatti, Priscilla B.; Araujo, Elaine B.; Mesquita, Carlos H. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)], e-mail: mflima@ipen.br

    2009-07-01

    The use of compartmental analysis allows the mathematical separation of tissues and organs to determinate the concentration of activity in each fraction of interest. Although the radiochemical purity must observe Pharmacopoeia specification (values upper 95%), very lower contains of free radionuclides could contribute significantly as dose in the neighborhood organs and make tumor up take studies not viable in case of radiopharmaceutical on the basis of labeled peptides. Animal studies with a product of Lutetium-177 labeled Bombesin derivative ({sup 177}Lu-BBNP) developed in IPEN-CNEN/SP and free Lutetium-177 developed in CNEA/EZEIZA was used to show how subtract free {sup 177}Lu contribution over {sup 177}Lu-BBNP to estimate the radiopharmaceutical potential as diagnosis or therapy agent. The first approach of the studies included the knowledge of chemical kinetics and mimetism of the Lutetium and the possible targets of the diagnosis/therapy to choose the possible models to apply over the sampling standard methods used in experimental works. A model with only one physical compartment (whole body) and one chemical compartment ({sup 177}Lu-BBNP) generated with the compartmental analysis protocol ANACOMP showed high differences between experimental and theoretical values over 2.5 hours, in spite of the concentration of activity had been in a good statistics rang of measurement. The values used in this work were residence time from three different kinds of study with free {sup 177}Lu: whole body, average excretion and maximum excretion as a chemical compartment. Activity concentration values as time function in measurements of total whole body and activity measurement in samples of blood with projection to total circulating blood volume with {sup 177}Lu-BBNP. Considering the two sources of data in the same modeling a better consistence was obtained. The next step was the statistic treatment of biodistribution and dosimetry in mice (Balb C) considering three chemical

  4. Anti-cancer, pharmacokinetic and biodistribution studies of cremophor el free alternative paclitaxel formulation.

    Science.gov (United States)

    Jain, Subheet K; Utreja, Puneet; Tiwary, Ashok K; Mahajan, Mohit; Kumar, Nikhil; Roy, Partha

    2014-01-01

    The aim of the present investigation is to determine the in vivo potential of previously developed and optimized Cremophor EL free paclitaxel (CF-PTX) formulation consisting of soya phosphatidylcholine and biosurfactant sodium deoxycholate. CF-PTX was found to have drug loading of 6 mg/ml similar to Cremophor EL based marketed paclitaxel formulation. In the present study, intracellular uptake, repeated dose 28 days sub-acute toxicity, anti-cancer activity, biodistribution and pharmacokinetic studies were conducted to determine in vivo performance of CF-PTX formulation in comparison to marketed paclitaxel formulation. Intracellular uptake of CF-PTX was studied using A549 cells by fluorescence activated cell sorting assay (FACS) and fluorescence microscopy. In vivo anti-cancer activity of CF-PTX was evaluated using Ehrlich ascites carcinoma (EAC) model in mice followed by biodistribution and pharmacokinetic studies. FACS investigation showed that fluorescence marker acridine orange (AO) solution showed only 19.8±1.1% intracellular uptake where as significantly higher uptake was observed in the case of AO loaded CF-PTX formulation (85.4±2.3%). The percentage reduction in tumor volume for CF-PTX (72.5±2.3%) in EAC bearing mice was found to be significantly (p<0.05) higher than marketed formulation (58.6±2.8%) on 14th day of treatment. Pharmacokinetic and biodistribution studies showed sustained plasma concentration of paclitaxel depicted by higher mean residence time (MRT; 18.2±1.8 h) and elimination half life (12.8±0.6 h) with CF-PTX formulation as compared to marketed formulation which showed 4.4±0.2 h MRT and 3.6±0.4 h half life. The results of the present study demonstrated better in vivo performance of CF-PTX and this formulation appears to be a promising carrier for sustained and targeted delivery of paclitaxel.

  5. 131I labeling of tamoxifen and biodistribution studies in rats

    International Nuclear Information System (INIS)

    Biber Muftuler, F.Z.; Unak, P.; Teksoz, S.; Acar, C.; Yolcular, S.; Yuerekli, Y.

    2008-01-01

    Tamoxifen [TAM ([Z]-2-[4-(1,2-diphenyl-1-di-butenyl)-phenoxy]-N,N-dimethylethanamine)] has been used as an antiestrogen drug for treatment and prevention of human breast cancer. Tamoxifen was labeled with 131 I using iodogen as an oxidizing agent. Mass spectroscopy of the cold standard showed that the labeling occurs in ortho position to the phenyl ether position of TAM as expected. Quality control, radiochemical yield and stability were established using the radioelectrophoresis method. The radiolabeled compound maintained its stability throughout working period of 24 h. Scintigraphic imaging was performed and tissue distribution was determined in Albino Wistar rats. According to biodistribution and imaging experiments the radiolabeled compound presented estrogen receptor (ER) specificity and it was uptaken by endometrium as well as breast tissue

  6. Biodistribution study of [I-123] ADAM in mice brain using quantitative autoradiography

    International Nuclear Information System (INIS)

    Lin, K.J.; Yen, T.C.; Tzen, K.Y.; Ye, X.X.; Hwang, J.J.; Wey, S.P.; Ting, G.

    2002-01-01

    Aim: Autoradiography with radioluminography is a delicate method to characterize newly developed radiotracers and to apply them to pharmacological studies. Herein, we reported a biodistribution result of [I-123] ADAM (2-((2-((dimethylamino)methyl)phenyl)thio)-5- iodophenylamine) in mice brain quantitatively using imaging plates. Materials and Methods: 1mCi [I-123] ADAM was injected into male ICR mice through tail veins. Brains were removed at sequential time points ranging from 0.5hr to 4hr after injection. The whole brain was cut into 14mm thick coronal sections using a cyrotome. The sections were thaw-mounted on glass plate and apposed placed on an imaging plate with filter paper standards for 24 hours. Imaging reading was done by a Fuji FLA5000 device. Regions of interest were placed on the globus pallidus, hypothalamus, substantia nigra, raphe nuclei and cerebellum corresponding to the sterotaxic atlas, and the PSL/mm 2 values were measured. The specific binding was expressed as the ratios of (targets - cerebellum) to cerebellum. Results: Autoradiography study of brain showed that the [I-123] ADAM was accumulated at serotonin transporter rich sites, including the olfactory tubercle, globus pallidus, thalamus nuclei, hypothalamus, substantia nigra, interpeduncular nucleus, amygdala and raphe nuclei. Biodistribution of [I-123] ADAM in mice brain using quantitative autoradiography method showed a high specific binding in the substantia nigra and hypothalamus and the time-activity curve peaked at 120 min post-injection. Compatible specific binding result was achieved in the region of hypothalamus as compared with previous study by other group using conventional tissue micro-dissection method (Synapse 38:403-412, 2000). However, higher specific binding was observed in certain small brain regions including substantia nigra, raphe nuclei due to improved spatial resolution of the quantitative autoradiography technique. Conclusion: Our result showed that the

  7. Single dose toxicity and biodistribution studies of [{sup 18}F] fluorocholine

    Energy Technology Data Exchange (ETDEWEB)

    Campos, Danielle C.; Santos, Priscilla F., E-mail: dcc@cdtn.br [Universidade Federal de Minas Gereais (INCT-MM/UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina. Instituto Nacional de Ciencia e Tecnologia de Medicina Molecular; Silveira, Marina B.; Ferreira, Soraya Z.; Malamut, Carlos; Silva, Juliana B. da, E-mail: radiofarmacoscdtn@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Unidade de Pesquisa e Producao de Radiofarmacos; Souza, Cristina M.; Campos, Liliane C.; Ferreira, Enio; Araujo, Marina R.; Cassali, Geovanni D., E-mail: cassalig@icb.ufmg.br [Universidade Federal de Minas Gerais (LPC/UFMG), Belo Horizonte, MG (Brazil). Lab. de Patologia Comparada

    2013-07-01

    [{sup 18}F]Fluorocholine ({sup 18}FCH) is a valuable tool for non-invasive diagnosis using positron emission tomography (PET). This radiotracer has been proven to be highly effective in detecting recurrences and staging prostate cancer, diagnoses brain, breast, and esophageal tumors and also hepatocellular carcinoma. The higher uptake of fluorocholine by malignant tumors results from increased choline kinase activity due to accelerated cell multiplication and membrane formation. According to the Brazilian Health Surveillance Agency (ANVISA), radiopharmaceuticals have to be registered before commercialization. The aim of this work was to evaluate single dose toxicity and biodistribution of {sup 18}FCH in mice, since preclinical safety studies are required for register. Experimental procedures were approved by the Ethics Committee on Animal Use (CEUA-IPEN/SP). Single dose toxicity and biodistribution studies were conducted in Swiss mice. No signs of toxicity were observed during clinical trial. No changes in the parameters which were examined, such as: body weight, food consumption, clinical pathology parameters or lesions microscopic were noted. Biodistribution results indicated high physiological tracer uptake in kidney, liver and heart 30 min after injection. Lower activities were recorded in other organs/tissues: pancreas, intestine, spleen, bone, bladder, muscle, brain and blood. Initial preclinical investigations showed no toxic effects of {sup 18}FCH at investigated doses and a biodistribution profile very similar to other reports in literature. This information is essential to support future human trials. (author)

  8. Technetium-99m as alternative to produce somatostatin-labeled derivatives: comparative biodistribution evaluation with 111In-DTPA-octreotide

    International Nuclear Information System (INIS)

    Melo, Ivani B.; Buchpiguel, Carlos Alberto; Ueda, Laura T.; Araujo, Elaine B. de; Muramoto, Emiko; Barboza, Marycel F. de; Mengatti, Jair; Silva, Constancia P.G. da

    2008-01-01

    Synthetic somatostatin (SST) analogues have been used in the preparation of receptor-specific radiopharmaceuticals for diagnostic and therapy of neuroendocrine (NE) tumors. 111 In-DTPA-Octreotide (OctreoScan®) has found useful for imaging a range of tumors, including NE cancer, carcinoide and lymphoma. Unfortunately, 111 In is a high-cost cyclotron produced radioisotope with gamma emission not so suitable for scintigraphic images and for dosimetry like 99m Tc. This work studied the labeling conditions with 99m Tc and biological distribution in Swiss mice of two SST analogs (HYNIC-Tyr 3 -Octreotide and HYNICTyr 3 - Octreotate) and compared the biodistribution pattern with 111 In-DTPA-Octreotide. 99 mTc-HYNIC-Tyr 3 - Octreotate ( 99m Tc-HYNIC-TATE) and 99m Tc-HYNIC-Tyr 3 -Octreotide ( 99m Tc-HYNIC-OCT) were produced by labeling conditions using tricine and EDDA as coligands. 111 In-DTPA-Octreotide ( 111 In-DTPA-OCT) was produced by labeling DTPA-Octreotide with 111 InCl 3 (Nordion). Radiochemical purity of labeled preparations was determined by ITLC-SG. Biological distribution studies were performed after injection of radiopharmaceuticals on Swiss mice. Labeling procedures resulted on high radiochemical yield for all three preparations and the labeled products presented high in vitro stability. Biological distribution studies evidenced similar general biodistribution of 99m Tc-labeled peptides when compared with indium-labeled peptide with fast blood clearance and elimination by urinary tract. Kidneys uptake of 99 mTc-HYNIC-TATE are similar to 111 In-DTPA-Octreotide, and both are significantly higher than 99 mTc-HYNIC-OCT. All labeled peptides presented similar uptake on liver, but the retention in time at intestines, particularly at large intestine, was more expressive for 111 In-labeled peptide. The %ID of 99m Tc-HYNIC-OCT and 99m Tc-HYNIC-TATE in organs with high density of SST receptors like pancreas and adrenals were significant and similar to obtained for 111

  9. 99mTc complexes of benzimidazole and benzoxazole ligands and their biodistribution studies

    International Nuclear Information System (INIS)

    Kothari, K.; Manju, S.; Pillai, M.R.A.; Rath, N.; Dash, K.C.; Sarma, H.D.

    1997-01-01

    Complexation studies of 2 (2' -hydroxyphenyl)benzimidazole (HPBI) and 2(2' -pyridyl)benzoxazole (PBO) with 99m Tc were carried out. The complexes were characterised by TLC, paper electrophoresis and solvent extraction. The ligand HPBI forms complex in high yield (>90%). Biodistribution studies carried out with 99m Tc-HPBI complex in Swiss Albino mice showed rapid clearance of the complex from blood and excretion of the activity through hepatobiliary system. (author). 2 refs., 1 fig., 3 tabs

  10. Direct comparison of radiation dosimetry of six PET tracers using human whole-body imaging and murine biodistribution studies

    International Nuclear Information System (INIS)

    Sakata, Muneyuki; Oda, Keiichi; Toyohara, Jun; Ishii, Kenji; Nariai, Tadashi; Ishiwata, Kiichi

    2013-01-01

    We investigated the whole-body biodistributions and radiation dosimetry of five 11 C-labeled and one 18 F-labeled radiotracers in human subjects, and compared the results to those obtained from murine biodistribution studies. The radiotracers investigated were 11 C-SA4503, 11 C-MPDX, 11 C-TMSX, 11 C-CHIBA-1001, 11 C-4DST, and 18 F-FBPA. Dynamic whole-body positron emission tomography (PET) was performed in three human subjects after a single bolus injection of each radiotracer. Emission scans were collected in two-dimensional mode in five bed positions. Regions of interest were placed over organs identified in reconstructed PET images. The OLINDA program was used to estimate radiation doses from the number of disintegrations of these source organs. These results were compared with the predicted human radiation doses on the basis of biodistribution data obtained from mice by dissection. The ratios of estimated effective doses from the human-derived data to those from the mouse-derived data ranged from 0.86 to 1.88. The critical organs that received the highest absorbed doses in the human- and mouse-derived studies differed for two of the six radiotracers. The differences between the human- and mouse-derived dosimetry involved not only the species differences, including faster systemic circulation of mice and differences in the metabolism, but also measurement methodologies. Although the mouse-derived effective doses were roughly comparable to the human-derived doses in most cases, considerable differences were found for critical organ dose estimates and pharmacokinetics in certain cases. Whole-body imaging for investigation of radiation dosimetry is desirable for the initial clinical evaluation of new PET probes prior to their application in subsequent clinical investigations. (author)

  11. Formulation of 68Ga BAPEN kit for myocardial positron emission tomography imaging and biodistribution study

    International Nuclear Information System (INIS)

    Yang, Bo Yeun; Jeong, Jae Min; Kim, Young Joo; Choi, Jae Yeon; Lee, Yun-Sang; Lee, Dong Soo

    2010-01-01

    Introduction: Tris(4,6-dimethoxysalicylaldimine)-N,N'-bis(3-aminopropyl) -N,N'-ethylenediamine (BAPEN), a tris(salicylaldimine) derivative, is a heart positron emission tomography (PET) agent when labeled with 68 Ga. However, its labeling requires complicated and time-consuming procedures. In this study, the authors formulated a new BAPEN kit for convenient 68 Ga labeling. Methods: BAPEN (0.25 mg) kits were prepared by dispensing its solution in 1 M sodium acetate buffer (pH 5.5) into sterile vials and lyophilization. The prepared kits were labeled with generator-eluted 68 Ga in 0.1 N HCl. Stability in human serum was tested. Expiration date was determined by accelerated testing according to US Food and Drug Administration guidelines. A Biodistribution study was performed in normal mice after injection via tail vein. Results: The prepared kits achieved radiolabeling efficiencies in excess of 95% and showed a shelf-life of 98 days at 25 deg. C and 64.3 months at 4 deg. C. 68 Ga-BAPEN was found to be stable in human serum at 37 deg. C for at least 1 h. Furthermore, a biodistribution study revealed high heart uptake (10.8% ID/g, 1 h). Conclusions: The authors developed a BAPEN kit for convenient labeling with 68 Ga. The 68 Ga-BAPEN showed high stability and excellent biodistribution results in normal mice, which is required for myocardial PET imaging.

  12. New surface radiolabeling schemes of super paramagnetic iron oxide nanoparticles (SPIONs) for biodistribution studies.

    Science.gov (United States)

    Nallathamby, Prakash D; Mortensen, Ninell P; Palko, Heather A; Malfatti, Mike; Smith, Catherine; Sonnett, James; Doktycz, Mitchel J; Gu, Baohua; Roeder, Ryan K; Wang, Wei; Retterer, Scott T

    2015-04-21

    Nanomaterial based drug delivery systems allow for the independent tuning of the surface chemical and physical properties that affect their biodistribution in vivo and the therapeutic payloads that they are intended to deliver. Additionally, the added therapeutic and diagnostic value of their inherent material properties often provides extra functionality. Iron based nanomaterials with their magnetic properties and easily tailorable surface chemistry are of particular interest as model systems. In this study the core radius of the iron oxide nanoparticles (NPs) was 14.08 ± 3.92 nm while the hydrodynamic radius of the NPs, as determined by Dynamic Light Scattering (DLS), was between 90-110 nm. In this study, different approaches were explored to create radiolabeled NPs that are stable in solution. The NPs were functionalized with polycarboxylate or polyamine surface functional groups. Polycarboxylate functionalized NPs had a zeta potential of -35 mV and polyamine functionalized NPs had a zeta potential of +40 mV. The polycarboxylate functionalized NPs were chosen for in vivo biodistribution studies and hence were radiolabeled with (14)C, with a final activity of 0.097 nCi mg(-1) of NPs. In chronic studies, the biodistribution profile is tracked using low level radiolabeled proxies of the nanoparticles of interest. Conventionally, these radiolabeled proxies are chemically similar but not chemically identical to the non-radiolabeled NPs of interest. This study is novel as different approaches were explored to create radiolabeled NPs that are stable, possess a hydrodynamic radius of <100 nm and most importantly they exhibit an identical surface chemical functionality as their non-radiolabeled counterparts. Identical chemical functionality of the radiolabeled probes to the non-radiolabeled probes was an important consideration to generate statistically similar biodistribution data sets using multiple imaging and detection techniques. The radiolabeling approach

  13. Poly(n-butylcyanoacrylate nanoparticles for oral delivery of quercetin: preparation, characterization, and pharmacokinetics and biodistribution studies in Wistar rats

    Directory of Open Access Journals (Sweden)

    Bagad M

    2015-06-01

    Full Text Available Mayur Bagad, Zaved Ahmed KhanMedical Biotechnology Division, School of Biosciences and Technology, VIT University, Vellore Tamil Nadu, IndiaBackground: Quercetin (QT is a potential bioflavonol and antioxidant with poor bioavailability and very low distribution in the brain. A new oral delivery system comprising of poly(n-butylcyanoacrylate nanoparticles (PBCA NPs was introduced to improve the oral bioavailability of QT and to increase its distribution in the brain. Physicochemical characteristics, in vitro release, stability in simulated gastric fluid and intestinal fluids, and pharmacokinetics and biodistribution studies of QT-PBCA NPs coated with polysorbate-80 (P-80 were investigated.Objective: This study aimed to investigate the physicochemical characteristics, in vitro release, stability in simulated gastric fluid and intestinal fluids, and pharmacokinetics and biodistribution studies of QT-PBCA NPs coated with polysorbate-80 (P-80.Results: The results showed that QT-PBCA NPs and QT-PBCA NPs coated with P-80 (QT-PBCA+P-80 had mean particle sizes of 161.1±0.44 nm and 166.6±0.33 nm respectively, and appeared spherical in shape under transmission electron microscopy. The mean entrapment efficiency was 79.86%±0.45% for QT-PBCA NPs and 74.58%±1.44% for QT-PBCA+P-80. The in vitro release of QT-PBCA NPs and QT-PBCA+P-80 showed an initial burst release followed by a sustained release when compared to free QT. The relative bioavailability of QT-PBCA NPs and QT-PBCA+P-80 enhanced QT bioavailability by 2.38- and 4.93-fold respectively, when compared to free QT. The biodistribution study in rats showed that a higher concentration of QT was detected in the brain after the NPs were coated with P-80.Conclusion: This study indicates that PBCA NPs coated with P-80 can be potential drug carriers for poorly water-soluble drugs. These NPs were observed to improve the drugs’ oral bioavailability and enhance their transport to the brain

  14. Fragmentation, labeling and biodistribution studies of KS1/4, a monoclonal antibody

    International Nuclear Information System (INIS)

    Mohd, S.B.

    1987-01-01

    In this study, an IgG2a (KS1/4), a monoclonal antibody (MoAb) specific against a human lung adenocarcinoma (UCLA P-3) was successfully fragmented enzymatically to yield F(ab') 2 and Fab by using pepsin and papain, respectively. The kinetic of fragmentation of the MoAb was compared to that of human immunoglobulin G (IgG). A similar pattern of fragmentation was observed with both antibodies with a higher percentage yield of the F(ab') 2 and Fab obtained upon the fragmentation of the IgG by the enzymes. The KS1/4 and the two fragments were labeled with three different radionuclides, namely iodine-131, indium-111 and selenium-75. The radioiodination of the MoAb and the fragments was carried out by using a modified chloramine-T method. Radiometal labeling of the MoAb and the fragments with indium-111 was performed by using DTPA as a bifunctional chelating agent, while intrinsic labeling of the MoAb was done by culturing the hybridoma in the presence of 75 Se-methionine. The biodistribution of the radiolabeled MoAb, F(ab') 2 and Fab fragments were performed by injecting the preparations intravenously into nude mice bearing human lung adenocarcinoma

  15. Quantitative neutron capture radiography for studying the biodistribution of tumor-seeking boron-containing compounds

    International Nuclear Information System (INIS)

    Gabel, D.; Holstein, H.; Larsson, B.; Gille, L.; Ericson, G.; Sacker, D.; Som, P.; Fairchild, R.G.

    1987-01-01

    Biodistribution of two compounds presently considered for use in neutron capture therapy has been studied in mice carrying a transplantable Harding-Passey melanoma. A method is described by which quantitative assessment can be made of the boron distribution in whole-body sections of such animals. An alpha-particle-sensitive film is placed in close contact with a freeze-dried section of an animal and exposed to neutrons. The tracks visible after etching are analyzed optoelectronically in fields of 0.6 X 0.6 mm2 and compared to standards of boron homogeneously distributed in liver homogenates. The dynamic range of this method is about two orders of magnitude in concentration, with a lower detection limit of 0.1 to 0.01 ppm 10 B, depending on the rate of induction of spurious tracks by fast neutrons present in the neutron beam chosen. In a transplantable Harding-Passey melanoma in mice, it was found that the sulfhydryl boron hydride Na2B12H11SH presently used for therapy of glioblastoma clears blood, muscle, and brain very rapidly. Its accumulation in tumors was persistent for more than three days. A higher tumor accumulation was observed with its disulfide, which has been suggested for neutron capture therapy. For both compounds, a marked heterogeneity of boron distribution within one tumor was found

  16. Iron-EHPG as an hepatobiliary MR contrast agent: initial imaging and biodistribution studies

    International Nuclear Information System (INIS)

    Lauffer, R.B.; Greif, W.L.; Stark, D.D.; Vincent, A.C.; Saini, S.; Wedeen, V.J.; Brady, T.J.

    1988-01-01

    A paramagnetic relaxation agent targeted to functioning hepatocytes of the liver and excreted into the bile would be useful in the enhancement of normal liver and biliary anatomy in MR imaging. We sought to demonstrate the feasibility of this approach using the prototype hepatobiliary MR contrast agent, iron(III) ethylenebis-(2-hydroxyphenylglycine) (Fe(EHPG) - ). The biodistribution, relaxation enhancement, and imaging characteristics of Fe(EHPG) - were compared to those of the non-specific iron chelate iron(III) diethylenetriaminepentaacetic acid (Fe(DTPA) 2- ), which has a comparable effect on water proton relaxation times. (author)

  17. 99m Tc-tazobactam, a novel infection imaging agent: Radiosynthesis, quality control, biodistribution, and infection imaging studies.

    Science.gov (United States)

    Rasheed, Rashid; Naqvi, Syed Ali Raza; Gillani, Syed Jawad Hussain; Zahoor, Ameer Fawad; Jielani, Asif; Saeed, Nidda

    2017-05-15

    The radiolabeled drug 99m Tc-tazobactam ( 99m Tc-TZB) was developed and assessed as an infection imaging agent in Pseudomonas aeruginosa and Salmonella enterica infection-induced animal models by comparing with inflammation induced animal models. Radiosynthesis of 99m Tc-TZB was assessed while changing ligand concentration, reducing agent concentration, pH, and reaction time while keeping radioactivity constant (~370 MBq). Percent labeling of the resulting complex was measured using paper chromatography and instant thin layer chromatography. The analysis of the 99m Tc-TZB complex indicated >95% labeling yield and electrophoresis revealed complex is neutral in nature. The biodistribution study also showed predominantly renal excretion; however liver, stomach, and intestine also showed slight tracer agent uptake. The agent significantly accumulated in Pseudomonas aeruginosa and Salmonella enterica infection induced tissues 3.58 ± 0.26% and 2.43 ± 0.42% respectively at 1 hour postinjection. The inflamed tissue failed to uptake noticeable activity at 1 hour time point. The scintigraphic study results were found in accordance with biodistribution pattern. On the basis of our preliminary results, the newly developed 99m Tc-TZB can be used to diagnose bacterial infection and to discriminate between infected and inflamed tissues. Copyright © 2017 John Wiley & Sons, Ltd.

  18. Boron biodistribution study in colorectal liver metastases patients in Argentina

    International Nuclear Information System (INIS)

    Cardoso, J.; Nievas, S.; Pereira, M.; Schwint, A.; Trivillin, V.; Pozzi, E.; Heber, E.; Monti Hughes, A.; Sanchez, P.; Bumaschny, E.; Itoiz, M.; Liberman, S.

    2009-01-01

    Ex-situ BNCT for multifocal unresectable liver metastases employing whole or partial autograft techniques requires knowledge of boron concentrations in healthy liver and metastases following perfusion and immersion in Wisconsin solution (W), the procedure employed for organ preservation during ex-situ irradiation. Measurements of boron concentration in blood, liver and metastases following an intravenous infusion of BPA-F in five colorectal liver metastases patients scheduled for surgery were performed. Tissue samples were evaluated for boron content pre and post perfusion and immersion in W. Complementary histological studies were performed. The data showed a dose-dependent BPA uptake in liver, a boron concentration ratio liver/blood close to 1 and a wide spread in the metastases/liver concentration ratios in the range 0.8-3.6, partially attributable to histological variations between samples. Based on the boron concentrations and dose considerations (liver≤ 15 Gy-Eq and tumor≥40 Gy-Eq) at the RA-3 thermal neutron facility (mean flux of about (6±1)x10 9 n cm -2 s -1 ), ex-situ treatment of liver metastases at RA-3 would be feasible.

  19. Comparing in vivo biodistribution with radiolabeling and Franz cell permeation assay to validate the efficacy of both methodologies in the evaluation of nanoemulsions: a safety approach

    International Nuclear Information System (INIS)

    Cerqueira-Coutinho, C S; De Campo, V E B; Mansur, C R E; Rossi, A L; Veiga, V F; Holandino, C; Freitas, Z M F; Ricci-Junior, E; Santos, E P; Santos-Oliveira, R

    2016-01-01

    The Franz cells permeation assay has been performed for over 25 years. However, the advent of nanotechnology created a whole new world, especially with regard to topical products. In this new global scenario an increasing number of nanostructure-based delivery systems (NDSs) have emerged and a global warning relating to the safety of these NDSs is arising. This work studied the efficacy of the Franz cells assay, comparing it with the radiolabeling biodistribution test. For this purpose a formulation of sunscreen based on an NDS was developed and characterized. The results demonstrated both that the NDS did not present in vitro cytotoxicity and that the radiolabeling biodistribution test is more precise for the evaluation of NDS cosmetics than the Franz cells assay, since it detected the permeation of the NDS at a picogram order. Due to this fact, and considering all the concerns related to NDSs and nanoparticles in general, more precise methods must be used in order to guarantee the safe use of these new classes of products. (paper)

  20. Biodistribution studies of 99mTc-labeled myoblasts in a murine model of muscular dystrophy

    International Nuclear Information System (INIS)

    Colombo, F.R.; Torrente, Y.; Casati, R.; Benti, R.; Corti, S.; Salani, S.; D'Angelo, M.G.; DeLiso, A.; Scarlato, G.; Bresolin, N.; Gerundini, P.

    2001-01-01

    The purpose of this study was twofold: first, to evaluate the myoblast labeling of various 99m Tc complexes and to select the complex that best accomplishes this labeling, and second to evaluate the biodistribution of myoblasts labeled with this complex using mice with MDX muscular dystrophy (the murine homologue of Duchenne's muscular dystrophy). The following ligands were used to prepare the corresponding 99m Tc complexes: hexakis-methoxy-isobutyl-isonitrile (MIBI), bis(2-ethoxyethyl)diphosphinoethane (Tf), (RR,SS)-4,8-diaza-3,6,6,9-tetramethyl-undecane-2,10-dione-bisoxime (HM-PAO), bis(N-ethyl)dithiocarbamate (NEt), and bis(N-ethoxy, N-ethyl)dithiocarbamate (NOEt). One million murine myoblasts were incubated for 30-60 minutes with 5 mCi of each of the 99mTc complexes prepared from the above ligands. Viability was assessed by microscopic counting after trypan blue staining, and the radioactivity absorbed in the cells was measured after centrifugation. The compound with the highest uptake in cellular pellets was [ 99m Tc]N-NOEt. The biodistribution of myoblasts labeled with this complex was evaluated after intraaortic injection in dystrophic mice. Such an approach has the potential of effecting widespread gene transfer through the bloodstream to muscles lacking dystrophin

  1. Preparation, quality control and biodistribution studies of [61Cu]-oxinate for PET tumor imaging

    International Nuclear Information System (INIS)

    Jalilian, A.R.; Yousefnia, H.; Garousi, J.; Shafaii, K.; Bolourinovin, F.; Zolghadri, S.; Faghihi, R.

    2009-01-01

    Targeting apoptosis is an interesting issue in molecular imaging and various modalities have been presented. However, recent experiences in nuclear pharmacy demonstrated the application of small tracer molecules is more desired. This work was conducted for production of a radiolabeled copper complex, i.e. Cu-oxinate as a potential PET tracer for apoptosis imaging in oncology. Cu-61 was prepared by natural zinc target irradiation with 22 MeV protons (150 μA) via the nat Zn(p, xn) 61 Cu nuclear reaction with a yield of 3.33 mCi/μAh. In order to obtain the best labeling method, optimization reactions were performed for pH, temperature and concentration followed by solid phase extraction. Biodistribution of the tracer was studied in wild-type and fibrosarcoma bearing mice. Under the optimized conditions, radio-thin-layer chromatography (RTLC) and HPLC showed radiochemical purities of 99.99% and 97% respectively (with a minimum specific activity of 16 Ci/mM). Biodistribution of the tracer in fibrosarcoma bearing mice demonstrated a significant tumor uptake after 3 h. Tumor:blood and tumor:muscle ratios were 2.0 and 6.0 after 3 h, respectively. (authors)

  2. Synthesis of DOTMP and biodistribution and imaging study of 177-Lu-DOTMP

    International Nuclear Information System (INIS)

    Deng Xinrong; Luo Zhifu; Xiang Xueqin; Li Fenglin; Fan Caiyun; Liu Zihua; Ye Zhaoyun; Li Hongyu; Chen Yang; Zhuang Ling

    2012-01-01

    Cyclen (1, 4, 7, 10-tetraazacyclododecane) and H 3 PO 3 was used to synthesis DOTMP (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-Tetraamino methylenephosphonate). 177 Lu was produced by irradiating enriched lutetium oxide ( 176 Lu 2 O 3 ) with thermal neutron flux of 2' × 10 13 n/cm 2 /S in swimming pool reactor (SPR) for 10 days. And then DOTMP was labelled by 177 Lu. The biodistribution of 177 Lu-DOTMP in model mice bearing S180 sarcoma and SPECT imaging in Japanese white rabbit were also carried out. The results showed that the total activity of 177 LuCl 3 solution obtained was 9.19 × 10 5 MBq after corresponding chemical process. According to the optimal condition of the labeling experiment, the labelling efficiency of 177 Lu-DOTMP was 99.4%. The results of biodistribution study indicated that 177 Lu-DOTMP eliminated rapidly from blood and was delivered to target bone. The radioactivity uptake was mainly in bone and less in other viscera. The results of SPECT imaging showed that the radioactivity was accumulated in bladder. 177 Lu-DOTMP was mainly excreted by kidney. The uptake of the activity in the skeleton was observed within 22 h postinjection and it became quite significant at 46 h post injection. It indicated that 177 Lu-DOTMP has good bone targeting and is worthy of further research. (authors)

  3. PEGylated superparamagnetic iron oxide nanoparticles labeled with 68Ga as a PET/MRI contrast agent. A biodistribution study

    International Nuclear Information System (INIS)

    Afsaneh Lahooti; Gruttner, Cordula; Parham Geramifar; Hassan Yousefnia

    2017-01-01

    The purpose of this study is to evaluate the biodistribution of polyethylene glycol (PEG) coated superparamagnetic iron oxide nanoparticles radiolabeled with 68 Ga in normal mice after intravenous administration of this probe. Three mice were sacrificed at specific time intervals. The biodistribution data revealed high uptake by liver and spleen (60.62 and 12.65 %ID/g at 120 min post injection for liver and spleen, respectively). The clearance of other organs was fast. These results suggest that 68 Ga-PEG-SPIONs has magnificent capabilities for applying in (PET-MRI) as a theranostic agent for detection of liver and spleen malignancies. (author)

  4. Preparation of crotalus venom radiolabeled with technetium99m as a tool for biodistribution study

    International Nuclear Information System (INIS)

    Pujatti, Priscilla Brunelli; Santos, Raquel Gouvea dos; Simal, Carlos Jorge Rodrigues

    2005-01-01

    Technetium- 99m ( 99m Tc) has been the radionuclide of choice for nuclear medicine procedures and experimental research. Because of its optimal nuclear properties, 99m Tc is suitable for high efficiency detection with the advantage of reduced radiological waste. Crotalus venom (CV) has been shown to reduce tumors in clinical studies and tissue distribution studies are very important for clinical use. The goal of this work was to obtain CV labeled with 99m Tc which preserves its biological activity. After labeling, biological activity was assessed by hemolytic activity evaluation. Labeled and crude venom caused indirect hemolysis provided that the incubation medium contained an exogenous source of lecithin. High yield radiolabeled-CV was obtained and biological activity was preserved. The results suggest that 99m Tc-CV can be a useful tool for biodistribution studies. (author)

  5. Comparative toxicity and biodistribution of copper nanoparticles and cupric ions in rats

    Directory of Open Access Journals (Sweden)

    Lee IC

    2016-06-01

    Full Text Available In-Chul Lee,1 Je-Won Ko,1 Sung-Hyeuk Park,1 Je-Oh Lim,1 In-Sik Shin,1 Changjong Moon,1 Sung-Hwan Kim,2 Jeong-Doo Heo,3 Jong-Choon Kim1 1College of Veterinary Medicine BK21 Plus Project Team, Chonnam National University, Gwangju, 2Jeonbuk Department of Inhalation Research, Korea Institute of Toxicology, Jeongeup, 3Gyeongnam Department of Environment and Toxicology, Korea Institute of Toxicology, Gyeongnam, Republic of Korea Abstract: Despite widespread use and prospective biomedical applications of copper nanoparticles (Cu NPs, their biosafety issues and kinetics remain unclear. Thus, the aim of this study was to compare the detailed in vivo toxicity of Cu NPs and cupric ions (CuCl2; Cu ions after a single oral dose. We determined the physicochemical characteristics of Cu NPs, including morphology, hydrodynamic size, zeta potential, and dissolution in gastric (pH 1.5, vehicle (pH 6.5, and intestinal (pH 7.8 conditions. We also evaluated the kinetics of Cu following a single equivalent dose (500 mg/kg of Cu NPs and Cu ions. Cu NPs had highest dissolution (84.5% only in gastric conditions when compared with complete dissolution of Cu ions under various physiological milieus. Kinetic analysis revealed that highest Cu levels in blood and tested organs of Cu NP-treated rats were 15%–25% lower than that of Cu ions. Similar to the case of Cu ions, Cu levels in the tested organs (especially liver, kidney, and spleen of Cu NP-treated rats increased significantly when compared with the vehicle control. However, delay in reaching the highest level and biopersistence of Cu were observed in the blood and tested organs of Cu NP-treated rats compared with Cu ions. Extremely high levels of Cu in feces indicated that unabsorbed Cu NPs or absorbed Cu ions were predominantly eliminated through liver/feces. Cu NPs exerted apparent toxicological effects at higher dose levels compared with Cu ions and showed sex-dependent differences in mortality, biochemistry, and

  6. Study of biodistribution properties of a new myocardial imaging agent 99Tcm-N-DBODC5

    International Nuclear Information System (INIS)

    Zhang Wanchun; Fang Wei; Wang Feng; Guo Feng; Guo Lin; He Zuoxiang; Wang Xuebin; Lin Bin; Tang Zhigang

    2007-01-01

    99 Tc m -N-DBODC5 for intravenous injection was prepared. The labelling yield was 95.0% ± 0.52%. Sixteen New Zealand rabbits were involved and planar gamma imaging was performed at 10 time-point after injection of 99 Tc m -N-DBODC5. The radioactivity changes of organs were calculated by regions of interest (ROI) analysis. The 16 rabbits were divided into 4 groups and were sacrificed at 30, 60, 120, and 180 min after iniection respectively. The activity for all excised organs were measured by γ-well counting for calculating radiouptake. Myocardial uptake for 99 Tc m -N-DBODC5 is high. Though myocardial uptake was lower than 99 Tc m -MIBI, the liver clearance for 99 Tc m -N-DBODC5 was more rapid than that of 99 Tc m MIBI. As early as 30 min after injection, 99 Tc m -N-DBODC5 heart-to-liver ratio is 0.98 ± 0.52 versus 0.56 ± 0.19 for 99 Tc m -MIBI (P 99 Tc m -N-DBODC5 heart-to-liver ratio improved to the peak value (1.18 ± 0.57), compared with 0.71 ± 0.29 for 99 Tc m -MIBI, P 99 Tc m - N-DBODC5 was keeping at a high level until 180 min. 99 Tc m -N-DBODC5 exhibited rapid lung clearance, similar to that of 99 Tc m -MIBI. The biodistribution in the isolated organs demonstrated the same trend. The rapid 99 Tc m -N-DBODC5 liver clearance may allow the earlier imaging, and overcome the photon scatter from the liver with high activity which interfered the inferoapical wall in myocardial images. 99 Tc m -N-DBODC5 is a promising new myocardial perfusion imaging agent with superior biodistribution properties. (authors)

  7. Synthesis and study of the biodistribution of a new molecule labeled by technetium 99M

    International Nuclear Information System (INIS)

    Ben alaya, Monia

    2008-01-01

    Cytectrenes are stable complexes, neutral, low-weight molecular and lipophilic, that's allowing them to be able to cross the intact BBB. These piperidinic molecules are synthesized by atomic exchange between tricarbonyl technetium with the Fe-Cyclopentadienyl fragment. The labelling reaction is carried out classically in oil bath at a temperature of 150 C during one hour. The reaction can be optimized using microwave. The study of the biodistribution in rat of these complexes after there purification shows high cerebral uptake. Cytectrenes can be used as a potential cerebral radiotracers for the early diagnosis of neuropsychiatric diseases. Cytectrene are able to cross the BBB regarding there lipophilicity. These characteristic allow them to cross the membrane of the white cells and to be used us a potential agent for the diagnosis of infection. (Author). 44 refs

  8. Effects of external magnetic field on biodistribution of nanoparticles: A histological study

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Tony [Department of Neurology, Chang Gung University College of Medicine and Memorial Hospital, 199 Tung-Hwa N Rd, Taipei, Taiwan (China); Hua, M.-Y. [Department of Chemical and Material Engineering, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, Taiwan (China); Chen Jyhping [Department of Chemical and Material Engineering, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, Taiwan (China); Wei, K.-C. [Department of Neurosurgery, Chang Gung University College of Medicine and Memorial Hospital, 199 Tung-Hwa N Rd, Taipei, Taiwan (China); Jung, S.-M. [Department of Pathology, Chang Gung University College of Medicine and Memorial Hospital, 199 Tung-Hwa N Rd, Taipei, Taiwan (China); Chang, Y.-J. [Department of Neurology, Chang Gung University College of Medicine and Memorial Hospital, 199 Tung-Hwa N Rd, Taipei, Taiwan (China); Jou, M.-J. [Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, Taiwan (China); Ma, Y.-H. [Department of Physiology and Pharmacology, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan 333, Taiwan (China)]. E-mail: yhma@mail.cgu.edu.tw

    2007-04-15

    This study investigates the effect of external magnetic fields on the biodistribution of nanoparticles (NP). A NdFeB magnet of 2.4 kG was externally applied over the left femoral artery or right kidney. The 250 nm dextran-coated Fe{sub 3}O{sub 4} NP was injected via tail vein in healthy rats, and organs were taken 1 or 24 h later. Prussian blue stain revealed that NP were more rapidly retained in the liver and spleen than in the lungs. NP aggregation observed in the kidney and femoral artery after application of external magnets was time dependent. Hollow organs such as the intestine, colon, and urinary bladder retained little NP.

  9. Effects of external magnetic field on biodistribution of nanoparticles: A histological study

    International Nuclear Information System (INIS)

    Wu, Tony; Hua, M.-Y.; Chen Jyhping; Wei, K.-C.; Jung, S.-M.; Chang, Y.-J.; Jou, M.-J.; Ma, Y.-H.

    2007-01-01

    This study investigates the effect of external magnetic fields on the biodistribution of nanoparticles (NP). A NdFeB magnet of 2.4 kG was externally applied over the left femoral artery or right kidney. The 250 nm dextran-coated Fe 3 O 4 NP was injected via tail vein in healthy rats, and organs were taken 1 or 24 h later. Prussian blue stain revealed that NP were more rapidly retained in the liver and spleen than in the lungs. NP aggregation observed in the kidney and femoral artery after application of external magnets was time dependent. Hollow organs such as the intestine, colon, and urinary bladder retained little NP

  10. Labeling of the peptide DOTA-tyr3-octreotate with radioiodine and biodistribution and AR42J neuroendocrine tumor affinity study in mice

    International Nuclear Information System (INIS)

    Nagamati, Lucio Takeshi

    2006-01-01

    Neuroendocrine tumors are rare and affect mainly the gastrointestinal tract but other systems are also affected like the skin, lungs and the nervous system. They are rich in type 2 somatostatin (SM) receptors (SSTR2) and may secrete hormones in excess. Synthetic SM derivative peptides are of great utility because presented bigger half life when compared to SM and can be used to clinical improvement of these patients due to its tumoral inhibitory action. The labeling of these peptides with radioisotopes allowed the acquisition of images with favourable cost-efficiency relationship and use in therapy. The peptide, DOTATyr3- octreotate (DOTATATE), has much more affinity for the SSTR2 receptor than the peptide commercially used nowadays, is easily radioiodinated and has a favourable biodistribution for diagnosis and treatment due to the presence of the chelator DOTA. We have studied the influence of various factors on the radiochemical purity of the labeled compound as labeling stability, absorbed dose estimation and biodistribution in normal and AR42J cell tumor-bearing Swiss and Nude mice. We observed easy and stable peptide radioiodination at peptide/radioiodine ( 131 I) ratio of 2.73 that produced a radiochemical species with retention time of 22.7 minutes at high performance liquid chromatography and presented a favourable biodistribution and dosimetry for imaging and therapy of patients with neuroendocrine tumors, just the opposite result observed the radioiodinated compounds without a chelator as described in the literature. Other molar peptide/radioiodine ratios did not showed good results, with various radiochemical species and unfavourable biodistribution. A possible dosimetric study in patients with neuroendocrine tumors may be carried out in the near future. (author)

  11. Comparative biodistribution profile of [131I]VIP and [131I]VIP10-28

    Directory of Open Access Journals (Sweden)

    Maria Tereza Colturato

    2005-10-01

    Full Text Available Various tumor cells express significantly higher amounts of VIP receptors (VIPR that provided the basis for the clinical use of radiolabeled VIP for the in vivo localization of tumors. This work studied the labeling of VIP and VIP10-28 with iodine-131 to compare the biological distribution of the labeled compounds in Nuce mice and the affinity for tumor cells. Both VIP and VIP10-28 peptides contain two tyrosine residues, in positions 10 and 22, that are theoretically equally susceptible to radioiodination employing oxidative electrophilic substitution using oxidizing agents like Chloramine T. Radiochemical purity of the reaction mixture was determined by electrophoresis and HPLC. The VIP peptide and the fragment were labeled with radioiodine with good radiochemical yield (above 96%. Suitable, but important differences can be observed in biological distribution studies. Comparatively, blood clearance was faster for labeled VIP and perhaps because of this, the uptake in tumor was lower, especially during the first hour. These differences observed in the biological distribution of the compounds can be related to the lipophilicity of the labeled compounds.Várias células tumorais expressam significantemente uma alta quantidade de receptores VIP (VIPR que determinam a base para o uso clínico de VIP radiomarcado para localização de tumores in vivo. Foi estudado neste trabalho a marcação do VIP e do fragmento VIP10-28 com iodo-131 comparando a distribuição biológica dos compostos marcados em camundongos Nude e sua afinidade pelas células tumorais. Ambos os peptídeos, VIP e VIP10-28. contém dois resíduos de tirosina nas posições 10 e 22, que teoricamente são igualmente susceptíveis pela substituição eletrofílica oxidativa do radioiodo utilizando Cloramina T como agente oxidante. A pureza radioquímica da mistura de reação foi determinada por eletroforese e cromatografia líquida de alta eficiência (CLAE. O VIP e fragmento foram

  12. Study of pharmacokinetics and biodistribution of radiolabelled receptor specific peptides in laboratory animals

    International Nuclear Information System (INIS)

    Laznickova, A.; Laznicek, M.; Trejtnar, F.; Maecke, H.R.; Mather, S.J.

    2001-01-01

    Somatostatin analogues labelled with different radionuclides could be employed for visualization or treatment of somatostatin receptor-positive tumours. An octapeptide 111 In [DTPA] octreotide is a synthetic radiolabelled somatostatin analogue which is currently in clinical use for detecting small neuroendocrine tumours and metastases not detectable by conventional means. However, several other somatostatin analogues have been under development and testing. The aim of this study was to radiolabel selected somatostatin receptor-binding octapeptides by different radionuclides and to report the results of their biodistribution in rats. The study was focused on the direct labelling of vapreotide (RC-160) with 99m Tc, on the conjugates of octreotide with DFO (desferrioxamine) for labelling with 67 Ga, and on the conjugates of octreotide and TOC with DOTA (tetraazacyclo-dodecane tetraacetic acid) for labelling with 88 Y. In the present study, 88 Y isotope instead of 90 Y was used as a label as 88 Y exhibits a longer half life of decay and emits gamma radiation which can be much more easily detected in biological samples than beta emission. The labelling of octreotide analogues with metal radionuclides using derived bifunctional chelates was simple, straightforward and consistently resulted in high radiochemical purity of the product. On the other hand, the application of the direct labelling method for labelling of RC-160 with 99m Tc was difficult because all procedures had to be made under nitrogen atmosphere and an attainment of high yield proved to be highly dependent on the accurate observation of reaction conditions. The labelling efficiency makes an immediate use of the radiolabelled RC-160 for biological studies impossible and it is necessary to involve the purification step into the labelling procedure. All radiolabelled receptor specific peptides under study exhibited rapid radioactivity clearance from the blood and most organs and tissues. On the other hand

  13. Clinical variables in radiotracer biodistributions

    International Nuclear Information System (INIS)

    Lentle, B.C.; Scott, J.R.; Schmidt, R.P.; Noujaim, A.A.

    1981-01-01

    Numerous iatrogenic causes of altered radiotracer biodistributions have been described. Cancer chemotherapy is a particularly potent cause of changed biodistributions while even a trivial matter such as preparing the skin with an iodine containing antiseptic may cause displacement of technetium from its compounds. In the blocking of thyroid uptake of radioiodines, there is good precedent for the manipulation of regional tissue dosimetry. It is possible to go beyond the mere cataloguing of these effects to look creatively at the subject of comparative tissue biodistributions and hence comparative dosimetry. Effects such as the clinical observation of the interference by cis-platinum with the usual biodistribution of radio-gallium suggests that such compounds can be used as probes each to lead to a better understanding of the mechanism of action of the other

  14. The biodistribution study of 99mTc labelled anti-CEA monoclonal antibody in tumor bearing nude mice

    International Nuclear Information System (INIS)

    Lou Zongxin

    1992-01-01

    The author report the optimal condition of 99m Tc labelling with anti-CEA monoclonal antibody using chelating of 99m Tc with dimethylformamide. The labelling rate of this method is 60%-80%, the radiochemical purity of labelling antibody over 90% and maintain its better immuno activity. The biodistribution of the tumor bearing nude mice demonstrates that as compared with the control group, 24 hours after the intraperitoneal injection the injected labelled antibody has its specific concentration in tumor tissue

  15. Biodistribution and stability studies of [18F]Fluoroethylrhodamine B, a potential PET myocardial perfusion agent

    International Nuclear Information System (INIS)

    Gottumukkala, Vijay; Heinrich, Tobias K.; Baker, Amanda; Dunning, Patricia; Fahey, Frederic H.; Treves, S. Ted; Packard, Alan B.

    2010-01-01

    Introduction: Fluorine-18-labeled rhodamine B was developed as a potential positron emission tomography (PET) tracer for the evaluation of myocardial perfusion, but preliminary studies in mice showed no accumulation in the heart suggesting that it was rapidly hydrolyzed in vivo in mice. A study was therefore undertaken to further evaluate this hypothesis. Methods: [ 18 F]Fluoroethylrhodamine B was equilibrated for 2 h at 37 deg. C in human, rat and mouse serum and in phosphate-buffered saline. Samples were removed periodically and assayed by high-performance liquid chromatography. Based on the results of the stability study, microPET imaging and a biodistribution study were carried out in rats. Results: In vitro stability studies demonstrated that [ 18 F]fluoroethylrhodamine B much more stable in rat and human sera than in mouse serum. After 2 h, the compound was >80% intact in rat serum but 18 F-labeled rhodamines should accumulate in the heart. Conclusions: [ 18 F]Fluoroethylrhodamine B is more stable in rat and human sera than it is in mouse serum. This improved stability is demonstrated by the high uptake of the tracer in the rat heart in comparison to the absence of visible uptake in the mouse heart. These observations suggest that 18 F-labeled rhodamines are promising candidates for more extensive evaluation as PET tracers for the evaluation of myocardial perfusion.

  16. Evaluation of fibrinogen-DTPA-99mTc. Biodistribution and imaging studies

    International Nuclear Information System (INIS)

    Lungu, V.; Mihailescu, G.; Fugaru, V.; Preda, A.

    1998-01-01

    Labelling with 99m Tc of fibrinogen, using DTPA anhydride as the bifunctional chelating agent, was studied in animals with venous thrombi. The parameters studied were: i) coupled reaction of 99m Tc with the fibrinogen-DTPA-Sn(II) in lyophilised form; ii) biodistribution studies of fibrinogen- 99m Tc in animals with venous thrombi, and iii) imaging studies by scintigraphic methods. The present study showed that the radiochemical purity of fibrinogen-DTPA- 99m Tc is > 95% for a maximum of 5 mCi (185 MBq) radioactivity of 99m Tc in the 1.5-2 ml volume. Above this level of radioactivity we found a drastic decrease in the radiochemical purity. The radioactivity ratio of the venous thrombi to the blood was 2.32+-0.45. The scintigraphic images showed a significant accumulation of fibrinogen-DTPA- 99m Tc in 1-hour-old thrombi, 1 hour after injection. From this results the diagnostic potential of fibrinogen-DTPA-Sn(II) in kit form was evaluated. (author)

  17. Labeling of vasoactive intestinal peptide (VIP) and VIP 10-28 fragment with radioiodine by direct method. Comparative study of the kinetics biodistribution and affinity for neuroendocrine tumor cells; Marcacao do peptideo intestinal vasoativo (VIP) e do fragmento VIP10-28 com radioiodo por metodo direto. Estudo comparativo da cinetica de biodistribuicao e da afinidade por celulas de tumor neuroendocrino

    Energy Technology Data Exchange (ETDEWEB)

    Colturato, Maria Tereza

    2005-07-01

    labeling mixture (simple purification) and to produce the radiopharmaceutical with high specific activity (complex purification and HPLC), were both efficient in the separation of the species in the reaction mixtures, as demonstrated by quality control procedures. Biological distribution studies were accomplished by venous administration of the radiopharmaceuticals in laboratory animals: biodistribution study of [{sup 131}I]VIP and [{sup 131}I]VIP 10-28 in normal Swiss mice, [{sup 131}I]VIP not purified and purified in Swiss mice with tumor and [{sup 131}I]VIP and [{sup 131}I]VIP 10-28 in Nude mice with tumor, scintigraphic images of [{sup 131/123}I]VIP and [{sup 123}I]VIP 10-28 in Swiss and Nude mice and Wistar rats with tumor. In vitro studies were accomplished to determine the percentage of [{sup 131}I]VIP and [{sup 131}I]VIP 10-28 bound to plasmatic proteins, stability study of [{sup 131}I]VIP and [{sup 131}I]VIP 10-28 in human plasma and the affinity and internalization of [{sup 131}I]VIP and [{sup 131}I]VIP 10-28 by tumour adenocarcinoma cells of human rectal colon (HT-29). All biological distribution studies demonstrated that both [{sup 131/123}I]VIP and [{sup 131/123}I]VIP 10-28 showed fast blood clearance, low renal and liver uptake, relative uptake in thyroid, showing in vivo dehalogenation and good uptake in tumour. Comparative biological distribution of the radiopharmaceuticals showed high uptake in the stomach for both peptides. The blood clearance of the fragment was slower, and influences the visualization of the tumour mass. The radiopharmaceuticals, [{sup 123}I]VIP and [{sup 123}I]VIP 10-28, were obtained with high radiochemical purity, but with low radiochemical yield when comparing with labeling procedures using iodine-131. Quality control assays of [{sup 123}I]Na indicated that the presence of radiochemical and radionuclide impurities influenced on labeling results. (author)

  18. {sup 99m}Tc radiolabeling and biodistribution study of scorpionfish (Scorpaena plumieri) venom in Swiss mice

    Energy Technology Data Exchange (ETDEWEB)

    Soprani, Juliana; Pujatti, Priscilla B.; Santos, Raquel G. dos [Centro de Desenvolvimento da Tecnologia Nuclear(CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Lab. de Radiobiologia]. E-mail: falejs@yahoo.com.br; priscillapujatti@yahoo.com.br; santosr@cdtn.br; Figueiredo, Suely G. de [Universidade Federal do Espirito Santo (UFES), Vitoria, ES (Brazil). Depto. de Ciencias Fisiologicas]. E-mail: suelygf@gmail.com; Simal, Carlos [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Medicina]. E-mail: csimal@brfree.com.br

    2007-07-01

    The use of radiotracers in research of animal venom has been scarce, although it allows an excellent approach to follow the process of biodistribution and kinetics of toxins, and tissue distribution studies are very important for clinical use. Our group has demonstrated that Scorpaena plumieri venom (SP) possess high antitumoral activity and can be a source of template molecules for the development of antitumoral drugs. The purpose of this study was to radiolabel SP with 99mTc and investigate its biodistribution profile. High labeling yield was obtained and the results suggest that [99mTc]SP can be an useful tool for in vivo studies. The analysis indicated that SP is excreted manly by the kidneys with a slow clearance rate. The significant [99mTc]SP uptake in the heart and lungs may explain, at least partially, the pulmonary edema and effect cardiac observed by the envenoming. (author)

  19. Labelling of 5-ethyl-5-phenylbarbituric acid with Technetium-99m: biodistribution study in Swiss mice

    International Nuclear Information System (INIS)

    Simoes, Susana B.E.; Oliveira, Marcia B.N. de; Gutfilen, Bianca; Bernardo-Filho, Mario; Alves, Andreia Coelho; Machado-Silva, Jose R.

    1996-01-01

    The 5-ethyl-5-phenylbarbituric acid (phenobarbital) is used as a sedative, hypnotic and anticonvulsant drug. We decided to label it with technetium-99m. In order to determine the optimal conditions, different concentrations of this drug were incubated with various stannous chloride solutions. Then, 99m Tc was added and chromatography was performed using 0.9% NaCl solution, acetone and n-butyl alcohol as the mobile phase. Using a solution of 0.01 mg/ml stannous chloride and 1.0 mg/ml phenobarbital over 92% of the radioactivity bound to phenobarbital 99m Tc-phenobarbital. In the biodistribution study, 99m Tc-phenobarbital was administered in mice intraperitoneal. The main uptake of the labeled drug was in the liver, blood, kidneys, spleen and stomach. The phenobarbital is also used as anesthetic drug in animals. Earlier studies confirm that this drug can dislocate the adult worms of Schistosoma mansoni to mesenteric vein towards the liver and portal vein, so that we used infected animals, radioactivity was not found in isolated worms and we can conclude that the phenobarbital has an indirect action in relation to the displacement of the worms. (author)

  20. Comparative assessment of the effects of salinomycin and monensin on the biodistribution of lead and some essential metal ions in mice, subjected to subacute lead intoxication.

    Science.gov (United States)

    Ivanova, Juliana; Gluhcheva, Yordanka; Dimova, Donika; Pavlova, Ekaterina; Arpadjan, Sonja

    2016-01-01

    In this study, we present a comparative assessment of the effects of two polyether ionophorous antibiotics (monensin and salinomycin) on the concentrations of lead (Pb), cooper (Cu), zinc (Zn) and iron (Fe) in the kidneys, spleen, liver and brain of Pb-intoxicated animals. Our data demonstrated that the intoxication of ICR male mice with Pb salt resulted in a significant accumulation of Pb in all studied organs of the mice compared to the untreated control animals. The biodistribution of the toxic metal was in the order kidneys>spleen>liver>brain. The treatment of the Pb-intoxicated animals with tetraethylammonium salts of monensic and salinomycinic acids significantly decreased the concentration of the toxic metal ion compared to the toxic control. The effect varied in the interval 38% (for kidneys) to 52% (for brain) compared to the toxic control group (Pb). The tetraethylammonium salt of salinomycinic acid was more effective in reducing the Pb concentration in the brain of the Pb-treated mice compared to monensin. Pb-intoxication did not affect significantly the Zn endogenous concentration compared to the normal values. The treatment of ICR male mice with Pb-salt decreased the Cu concentration in the spleen and increased the Cu concentration in the liver compared to the untreated control animals. The detoxification of the Pb-intoxicated mice with tetraethylammonium salts of salinomycinic and monensic acids restored the Cu concentration in the spleen, but did not affect the Cu levels in the liver. The Pb-intoxication of the ICR mice resulted in a significant decrease of the Fe-concentration in the spleen and liver compared to the untreated control animals. The administration of the tetraethylammonium salts of salinomycinic and monensic acids to the Pb-treated animals restored the levels of Fe in both organs. Copyright © 2015 Elsevier GmbH. All rights reserved.

  1. Biodistribution study of 153Sm-EDTMP produced by irradiation of natural and enriched Samarium, in rats

    International Nuclear Information System (INIS)

    Meftahi, M.; Bahrami Samani, A.; Babaei, M. H.; Shamsaei Zafarghandi, M.; Ghannadi Maragheh, M.

    2010-01-01

    ''1 53 Sm-EDTMP is one of the well known radiopharmaceuticals for pain palliation of bone metastases. Despite that, it is used just in a few countries. It is due to some reasons like being costly enriched samarium that usually used as target for irradiation and short half-life of 153 Sm. In this investigation, certain amounts of radiopharmaceuticals prepared by irradiation of enriched and natural samarium were injected to some normal rats. Then, the rodents were sacrificed and some of their organs were removed. All of the mentioned stages were performed in order to consider the possibility of exploiting natural samarium instead of enriched samarium by study of biodistribution of both radiopharmaceuticals in various organs especially in bone as the target tissue. At the end, the acceptable results were obtained using natural samarium in comparison with the enriched samarium from the point of view of the biodistribution studies.

  2. Synthesis and preliminary biodistribution studies of [131I]SIB-PEG4-CHC in tumor-bearing mice

    International Nuclear Information System (INIS)

    Xiaobei Zheng; Jing Yang; Xiaojiang Duan; Tingting Niu; Wangsuo Wu; Jianjun Wang; Feng Dong

    2011-01-01

    This work reports the synthesis and preliminary biodistribution results of [ 131 I]SIB-PEG 4 -CHC in tumor-bearing mice. The tributylstannyl precursor ATE-PEG 4 -CHC was synthesized by conjugation of ATE to amino pegylated colchicine NH 2 -PEG 4 -CHC. [ 131 I]SIB-PEG 4 -CHC was radiosynthesized by electrophilic destannylation of the precursor with a yield of ∼44%. The radiochemical purity (RCP) appeared to be >95% by a Sep-Pak cartridge purification. [ 131 I]SIB-PEG 4 -CHC was lipophilic and was stable at room temperature. Biodistribution studies in tumor-bearing mice showed that [ 131 I]SIB-PEG 4 -CHC cleared from background rapidly, and didn't deiodinate in vivo. However, the poor tumor localization excluded it from further investigations as a tumor-targeted radiopharmaceuticals. (author)

  3. Practicality of the cyclotron production of radiolanthanide 142Pr. A potential for therapeutic applications and biodistribution studies

    International Nuclear Information System (INIS)

    Mahdi Sadeghi; Bakht, M.K.; Leila Mokhtari

    2011-01-01

    Radiolanthanide praseodymium-142 (T 1/2 = 19.12 h, E β - = 2.162 MeV (96.3%), E γ = 1575 keV (3.7%)) due to its high β-emission and low specific γ-emission could not only be a therapeutic radionuclide, but also a suitable radionuclide in order for biodistribution studies. Conventionally, 142 Pr produces via 141 Pr(n,γ) 142 Pr reaction by irradiation in a low-fluence reactor and this study evaluates cyclotron reaction production of it. 142 Pr excitation function via nat La(α,n) 142 Pr, 142 Ce(p,n) 142 Pr, and nat Pr(d,p) 142 Pr reactions were calculated by TALYS-1.2 and EMPIRE-2.19beta codes, and with the data taken from the TENDL-2010 database. In addition, we compared them with the reported measurement by experimental data. Requisite thickness of targets was obtained by SRIM-2010 code for each reaction. The 142 Pr production yield was evaluated with attention to excitation function and stopping power. Similar to reactor produced 142 Pr; 141 Pr impurity exists in cyclotron produced 142 Pr while it could not be separated by chemical methods. Therefore, cyclotron and reactor produced 142 Pr will be in carrier added form. (author)

  4. Targeting of liver tumour in rats by selective delivery of holmium-166 loaded microspheres: a biodistribution study

    Energy Technology Data Exchange (ETDEWEB)

    Nijsen, F.; Rook, D.; Zonnenberg, B.; Klerk, J. de; Rijk, P. van; Schip, F. van het [Dept. of Nuclear Medicine, University Medical Center, Utrecht (Netherlands); Brandt, C. [Animal Inst., Utrecht Univ. (Netherlands); Meijer, R. [Dept. of Radiology, Univ. Medical Center, Utrecht (Netherlands); Dullens, H. [Dept. of Pathology, Univ. Medical Center, Utrecht (Netherlands); Hennink, W. [Dept. of Pharmaceutics, Utrecht Univ. (Netherlands)

    2001-06-01

    Intra-arterial administration of beta-emitting particles that become trapped in the vascular bed of a tumour and remain there while delivering high doses, represents a unique approach in the treatment of both primary and metastatic liver tumours. Studies on selective internal radiation therapy of colorectal liver metastases using yttrium-90 glass microspheres have shown encouraging results. This study describes the biodistribution of 40-{mu}m poly lactic acid microspheres loaded with radioactive holmium-166, after intra-arterial administration into the hepatic artery of rats with implanted liver tumours. Radioactivity measurements showed >95% retention of injected activity in the liver and its resident tumour. The average activity detected in other tissues was {<=}0.1%ID/g, with incidental exceptions in the lungs and stomach. Very little {sup 166}Ho activity was detected in kidneys (<0.1%ID/g), thereby indicating the stability of the microspheres in vivo. Tumour targeting was very effective, with a mean tumour to liver ratio of 6.1{+-}2.9 for rats with tumour (n=15) versus 0.7{+-}0.5 for control rats (n=6; P<0.001). These ratios were not significantly affected by the use of adrenaline. Histological analysis showed that five times as many large (>10) and medium-sized (4-9) clusters of microspheres were present within tumour and peritumoural tissue, compared with normal liver. Single microspheres were equally dispersed throughout the tumour, as well as normal liver parenchyma. (orig.)

  5. Targeting of VX2 Rabbit Liver Tumor by Selective Delivery of 3-Bromopyruvate: A Biodistribution and Survival Study

    Science.gov (United States)

    Vali, Mustafa; Vossen, Josephina A.; Buijs, Manon; Engles, James M.; Liapi, Eleni; Ventura, Veronica Prieto; Khwaja, Afsheen; Acha-Ngwodo, Obele; Shanmugasundaram, Ganapathy; Syed, Labiq; Wahl, Richard L.; Geschwind, Jean-Francois H.

    2009-01-01

    The aim of this study was to determine the biodistribution and tumor targeting ability of 14C-labeled 3-bromopyruvate ([14C]3-BrPA) after i.a. and i.v. delivery in the VX2 rabbit model. In addition, we evaluated the effects of [14C]3-BrPA on tumor and healthy tissue glucose metabolism by determining 18F-deoxyglucose (FDG) uptake. Last, we determined the survival benefit of i.a. administered 3-BrPA. In total, 60 rabbits with VX2 liver tumor received either 1.75 mM [14C]3-BrPA i.a., 1.75 mM [14C]3-BrPA i.v., 20 mM [14C]3-BrPA i.v., or 25 ml of phosphate-buffered saline (PBS). All rabbits (with the exception of the 20 mM i.v. group) received FDG 1 h before sacrifice. Next, we compared survival of animals treated with i.a. administered 1.75 mM [14C]3-BrPA in 25 ml of PBS (n = 22) with controls (n = 10). After i.a. infusion, tumor uptake of [14C]3-BrPA was 1.8 ± 0.2% percentage of injected dose per gram of tissue (%ID/g), whereas other tissues showed minimal uptake. After i.v. infusion (1.75 mM), tumor uptake of [14C]3-BrPA was 0.03 ± 0.01% ID/g. After i.a. administration of [14C]3-BrPA, tumor uptake of FDG was 26 times lower than in controls. After i.v. administration of [14C]3-BrPA, there was no significant difference in tumor FDG uptake. Survival analysis showed that rabbits treated with 1.75 mM 3-BrPA survived longer (55 days) than controls (18.6 days). Intra-arterially delivered 3-BrPA has a favorable biodistribution profile, combining a high tumor uptake resulting in blockage of FDG uptake with no effects on healthy tissue. The local control of the liver tumor by 3-BrPA resulted in a significant survival benefit. PMID:18591216

  6. A Comparison of Three Transarterial Lipiodol-Based Formulations for Hepatocellular Carcinoma: In Vivo Biodistribution Study in Humans

    International Nuclear Information System (INIS)

    Yu, Simon Chun Ho; Leung, Thomas Wai Tong; Lau, Wan Yee; Lee, Nelson; Hui, Edwin Pun; Yeo, Winnie; Lai, Paul Bo San; Mok, Tony Shu Kam

    2008-01-01

    This study aimed to evaluate and compare the biodistribution properties of three transarterial Lipiodol-based therapeutic regimens in human hepatocellular carcinoma (HCC). In this prospective study with 13 patients randomly allocated to one of three study groups, each of the patients received transcatheter intra-arterial administration into a solitary HCC with one of three different Lipiodol-based formulations: Lipiodol-ethanol mixture (LEM; Group A), Lipiodol alone (Group B), and Lipiodol and gelatin pledgets (Group C). With the use of radioactive iodine-131-labeled Lipiodol, each group was assessed for (1) pattern of Lipiodol accumulation in the lungs within the first 2 weeks as evaluated by single-photon emission computed tomography and (2) decomposition of Lipiodol formulation within the first 2 weeks as evaluated by radioactivity detected in peripheral blood and urine. The degree of Lipiodol retention in the tumor within the first 4 weeks was evaluated with CT. No statistically significant difference in Lipiodol accumulation in the lungs was detected among the three groups. However, the peak accumulation in the lungs was delayed 3 days for Group A compared to Groups B and C. The degree of Lipiodol retention within the tumor in Group A was significantly greater than that in Groups B and C on day 14 (p = 0.014) and day 28 (p = 0.013). This study showed that LEM is associated with a greater embolic effect in intrahepatic HCC at 4 weeks, and a comparable degree of lung shunting and decomposition rates, compared with ethanol-free Lipiodol formulations

  7. Studies of the radiolabeling and biodistribution of substance P using lutetium-177 as a radiotracer

    International Nuclear Information System (INIS)

    Lima, Clarice Maria de

    2011-01-01

    of methionine, using human M059J U-87 MG glioma cells and, showed the effect of oxidation of methionine on the cells binding. Biodistribution studies were performed in Nude mice with tumor model and Balb-c mice. Highest radiochemical purity (> 95%) associated with the highest specific activity of '1 77 Lu-DOTA-SP when the reaction time was 30 minutes, temperature of 90 degree C, 10 gμ of DOTA-SP, and the activity of 177 Lu of 185 MBq. The radiolabeled SP in optimized conditions remained stable at 2-8 degree C and in human serum for 4 hours. In vitro studies showed the binding to cell receptors and this binding was reduced when the peptide was presented in its oxidized form. The addition of methionine combined with gentisic acid prevented the oxidation of peptide and increased the stability of the labeled compound, particularly with high activity of 177 Lu, when using larger mass of DOTA-SP. In vivo studies results showed a favorable biodistribution kinetics of the compound and ability to bind to tumor cells. 177 Lu-DOTA-SP can be a useful tool for in vivo studies due to ease preparation, high stability and affinity for tumor cells. (author)

  8. BOPP revisited. A study on the toxicity, biodistribution and convection enhanced delivery of BOPP in the 9L intracerebral rat glioma model

    International Nuclear Information System (INIS)

    Kahl, S.B.; Koo, M.-S.; Ozawa, T.; Afzal, J.; Lamborn, K.R.; Deen, D.F.; Bollen, A.W.; Bauer, W.F.

    2006-01-01

    To evaluate and compare the toxicity and boron biodistribution of the boronated porphyrin BOPP when administered by either intravenous or convection enhanced delivery (CED). For the toxicity study, Fischer 344 rats were injected with graded concentrations of BOPP into the tail vein. For boron biodistribution studies, 9L tumor-bearing rats received BOPP either systematically or by CED. When given i.v. BOPP showed unacceptable toxicity in normal rats receiving doses of ≥60 mg/kg. In contrast, tumor bearing rats receiving BOPP by CED showed no evidence of toxic effects whatsoever. In the biodistribution study, the maximum tumor boron concentration was ∼21 μ/g at 48 h after i.v. injection, at which time the tumor/blood ratio was ∼1.2. Neither of these values is optimal. However, when BOPP was delivered directly into intracerebral tumors with CED, we obtained tumor boron concentrations much greater than those obtained by i.v. injection. For example, convection enhanced delivery of 1.5 mg BOPP produced an average tumor boron level of 519 μg/g and a tumor/blood ratio of ∼1850:1. Tumor/brain ratios of ∼9:1 (ipsilateral) and ∼41:1 (contralateral) were also found at this dose. We conclude that changing the method of BOPP delivery from i.v. to CED significantly enhances the boron concentration in tumors and produces very favorable tumor/blood and tumor/brain ratios with no concomittant systemic toxicity. (author)

  9. Study on biodistribution and imaging of radioiodinated antisense oligonucleotides in nude mice bearing human lymphoma

    International Nuclear Information System (INIS)

    Wang, R.F.; Shen, J.; Zhang, C.L.; Liu, M.; Guo, F.Q.

    2005-01-01

    The incidence of sporadic lymphoma has risen due to an increase in immunosuppressed patients, particularly those with human immunodeficiency virus (HIV) infection. Sometimes suspect lymphoma has an undetectable location and we can not get the pathological specimen. Management of lymphoma is also difficult because the persistence of a significant number of residual tumor cells after intensive treatment. These relative failures can be attributed to make us choose this study for opening a new diagnostic and therapeutic field of lymphoma from molecular level. Immunoglobulin (Ig) heavy chain framework region (FR) of V1 family have been verified to be a major determinant of malignant phenotype of V1 family B-cell lymphoma. Most of targets for tumor antisense therapy study are protooncogenes, such as c-myc, bc1-2, which are broad -spectrum tumor imaging agents. The aim of this study was to investigate the possibility of using radioiodine labeled FR antisense oligonucleotides (ASONs) as an imaging agent or antisense therapeutic radiopharmaceutical in lymphoma. A 18-mer partial phosphorothioate oligonucleotide sequence was synthesized and grafted in 5 ' with a tyramine group which was further labeled with 125 I or 131 I using the chloramine T method. Normal CD-1 mice were injected via a tail vein with 148 kBq of 125 I-FR-ASON (2∼3 μ g). Animals were sacrificed at 1, 2, 4 and 24 h and tissue samples were studied. Liposome-mediated 3.33 MBq of 131 I-FR-ASON (7 ∼ 9μ g) was injected intratumorally into tumor-bearing BALB/c mice (6 weeks after inoculation of 10 7 Namalwa cells) meanwhile liposome-mediated 131 I labeled sense oligonucleotides served as controls. Biodistribution was monitored by sequential scintigraphy and organ radioactivity measurement 24 h after injection. The percentage of the injected dose per gram (%ID/g) of tumor and tumor/ non-tumor tissue ratios (T/NT) were calculated for each group of mice and the difference between two groups was assessed. The 5

  10. A study on the synthesis, labeling and its biodistribution of estradiol derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Wook; Yang, Seung Dae; Suh, Yong Sup [College of Medicine, Dongguk Univ., Seoul (Korea, Republic of)] [and others

    2000-10-01

    Due to the heterogeneous receptor distribution and changes of receptor status over time, the biochemical measurement of estrogen receptor status of biopsy specimens is not sufficient to diagnose breast cancer. As a result, I-123 labeled estradiols have been applied for the diagnosis. The purpose of this study was to develop a suitable radioligand for imaging estrogen receptor-positive human breast tumors. Among the various estradiol derivatives, 17{alpha}-[{sup 123}I]iodovinyl estradiol ([{sup 123}]IVE) has been prepared from 17{alpha}-ethynyl estradiol. Labeling of E-17{alpha}-[{sup 123}I]iodovinyl estradiol ([{sup 123}]IVE] was carried out using peracetic acid with [{sup 123}I]Nal and Z-[{sup 123}I]IVE labelling was archived using chloamine T/HCL solution with [{sup 123}I]Nal. Labeling yield was determined by silica thin-layer chromatography (TLC) and radiochemical purity was measured by high performance liquid chromatography (HPLC). The biodistribution of E-[{sup 123}I]IVE was measured in immature female rats at 60 min, 120 min and 300 min after injection. The labeling yield of two isomers was 92% and 94% (E-[{sup 123}I]IVE and Z-[{sup 123}I]IVE, respectively). The radiochemical purity was more than 98% after purification. The highest uptake was observed at 120 min in uterus (3.11% ID/g for E-[{sup 123}I]IVE. These results suggest the possibility of using E-[{sup 123}I]IVE as an imaging agent for the evaluation of the presence of estrogen receptor in patients with breast cancer.

  11. A study on the synthesis, labeling and its biodistribution of estradiol derivatives

    International Nuclear Information System (INIS)

    Kim, Sang Wook; Yang, Seung Dae; Suh, Yong Sup

    2000-01-01

    Due to the heterogeneous receptor distribution and changes of receptor status over time, the biochemical measurement of estrogen receptor status of biopsy specimens is not sufficient to diagnose breast cancer. As a result, I-123 labeled estradiols have been applied for the diagnosis. The purpose of this study was to develop a suitable radioligand for imaging estrogen receptor-positive human breast tumors. Among the various estradiol derivatives, 17α-[ 123 I]iodovinyl estradiol ([ 123 ]IVE) has been prepared from 17α-ethynyl estradiol. Labeling of E-17α-[ 123 I]iodovinyl estradiol ([ 123 ]IVE] was carried out using peracetic acid with [ 123 I]Nal and Z-[ 123 I]IVE labelling was archived using chloamine T/HCL solution with [ 123 I]Nal. Labeling yield was determined by silica thin-layer chromatography (TLC) and radiochemical purity was measured by high performance liquid chromatography (HPLC). The biodistribution of E-[ 123 I]IVE was measured in immature female rats at 60 min, 120 min and 300 min after injection. The labeling yield of two isomers was 92% and 94% (E-[ 123 I]IVE and Z-[ 123 I]IVE, respectively). The radiochemical purity was more than 98% after purification. The highest uptake was observed at 120 min in uterus (3.11% ID/g for E-[ 123 I]IVE. These results suggest the possibility of using E-[ 123 I]IVE as an imaging agent for the evaluation of the presence of estrogen receptor in patients with breast cancer

  12. Clinical variables in radiotracer biodistributions

    International Nuclear Information System (INIS)

    Lentle, B.C.; Scott, J.R.; Schmidt, R.P.; Noujaim, A.A.

    1981-01-01

    Radionuclide dosimetry must, by its nature, define tissue irradiation in terms of mean exposure in a population of a statistically acceptable size. In the daily practice of clinical nuclear medicine there are, however, quite large variations in the biodistribution of tracers and thus in resulting radiation doses. Age is a variable, particularly in respect of bone-seeking tracers. Sex imposes variations in radiation dose on account of the differing anatomical configurations of the gonads. Breast uptake and excretion of certain tracers in women are additional variables. Activity and occupation are occasional variables. Numerous iatrogenic causes of altered radiotracer biodistributions have been described. Cancer chemotherapy is a particularly potent cause of changed biodistributions while even a trivial matter such as preparing the skin with an iodine containing antiseptic may cause displacement of technetium from its compounds. In the blocking of thyroid uptake of radioiodines, there is good precedent for the manipulation of regional tissue dosimetry. It is possible to go beyond the mere cataloguing of these effects to look creatively at the subject of comparative tissue biodistributions and hence comparative dosimetry. Effects such as the clinical observation of the interference by cis-platinum with the usual biodistribution of radio-gallium suggest that such compounds can be used as probes each to lead to a better understanding of the mechanism of action of the other

  13. A study of computational dosimetry and boron biodistribution for ex – situ lung BNCT at RA-3 Reactor

    International Nuclear Information System (INIS)

    Garabalino, M.A.; Trivillin, V. A.; Monti Hughes, A.; Pozzi, E.C.C.; Thorp, S.; Curotto, P; Miller, M.; Santa Cruz, G.A.; Saint Martin, G.; Schwint, A.E.; González, S.J.; Farías, R.O; Portu, A.; Ferraris, S.; Santa María, J.; Lange, F.; Bortolussi, S.; Altieri, S.

    2013-01-01

    Within the context of the preclinical ex-situ BNCT Project for the treatment of diffuse lung metastases, we performed boron biodistribution studies in a sheep model and computational dosimetry studies in human lung to evaluate the potential therapeutic efficacy of the proposed technique. Herein we report preliminary data that supports the use of the sheep model as an adequate human surrogate in terms of boron kinetics and uptake in clinically relevant tissues. Furthermore, the estimation of the potential therapeutic efficacy of the proposed treatment in humans, based on boron uptake values in the large animal model, yields promising tumor control probability values even in the most conservative scenario considered. (author)

  14. The synthesis of a new cardiac sympathetic nerve imaging agent N-[11C]CH3-dopamine and biodistribution study

    International Nuclear Information System (INIS)

    Yulin He; Weina Zhou; Xiangcheng Wang; Baoliang Bao; Guojian Zhang; Cheng Wang; Chunmei Wang; Xuemei Wang; Wei Fang

    2014-01-01

    In this study, we synthesized and characterized N-[ 11 C]methyl-dopamine ([ 11 C]MDA) for cardiac sympathetic nerve imaging. [ 11 C]MDA was synthesized by direct N-methylation of dopamine with [ 11 C]methyl iodide and purified by semi-preparation reverse high pressure liquid chromatography (HPLC). The total synthesis time was 45 min including HPLC purification. The radiochemical yields of [ 11 C]MDA was 20 ± 3 %, without decay correction. The radiochemical purity was >98 % and the specific activity was about 50 GBq/mmol. The biological properties of [ 11 C]MDA were evaluated by biodistribution study in normal mice. PET imaging was performed in healthy Chinese mini-swines. Biodistribution study showed that [ 11 C]MDA had high myocardium uptake. PET/CT imaging showed [ 11 C]MDA had clear and symmetrical myocardium uptake, which was blocked obviously by injecting imipramine hydrochloride. [ 11 C]MDA would be a promising candidate of radiotracer for cardiac sympathetic nervous system imaging. (author)

  15. Biodistribution and pharmacokinetic studies of a porphyrin dimer photosensitizer (Oxdime) by fluorescence imaging and spectroscopy in mice bearing xenograft tumors.

    Science.gov (United States)

    Khurana, Mamta; Ulrich, Sébastien; Kim, Anthony; Moriyama, Yumi; Netchev, George; Akens, Margarete K; Anderson, Harry L; Wilson, Brian C

    2012-01-01

    Herein, we present a study of the pharmacokinetics and biodistribution of a butadiyne-linked conjugated porphyrin dimer (Oxdime) designed to have high near-infrared (NIR) 2-photon absorption cross-section for photodynamic therapy (PDT). Changes in biodistribution over time were monitored in mice carrying B16-F10 melanoma xenografts, following intravenous injection. Using fluorescence imaging of live animals and analyzing isolated organs ex vivo at different time points between 30 min and 24 h after injection, accumulation of Oxdime was measured in several organs (heart, kidney and liver) and in tumor. The concentration in the plasma was about 5-10 times higher than in other tissues. The fluorescence signal peaked at 3-12 h after injection in most tissues, including the tumor and the plasma. The change in the fluorescence emission spectrum of the sensitizer over time was also monitored and a shift in the maximum from 800 to 740 nm was observed over 24 h, showing that the Oxdime is metabolized. Significant quantities accumulated in the tumor, indicating that this PDT sensitizer may be promising for cancer treatment. © 2012 Wiley Periodicals, Inc. Photochemistry and Photobiology © 2012 The American Society of Photobiology.

  16. Biodistribution studies of {sup 99m}Tc-labeled myoblasts in a murine model of muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Colombo, F.R. E-mail: colombof@policlinico.mi.it; Torrente, Y.; Casati, R.; Benti, R.; Corti, S.; Salani, S.; D' Angelo, M.G.; DeLiso, A.; Scarlato, G.; Bresolin, N.; Gerundini, P

    2001-11-01

    The purpose of this study was twofold: first, to evaluate the myoblast labeling of various {sup 99m}Tc complexes and to select the complex that best accomplishes this labeling, and second to evaluate the biodistribution of myoblasts labeled with this complex using mice with MDX muscular dystrophy (the murine homologue of Duchenne's muscular dystrophy). The following ligands were used to prepare the corresponding {sup 99m}Tc complexes: hexakis-methoxy-isobutyl-isonitrile (MIBI), bis(2-ethoxyethyl)diphosphinoethane (Tf), (RR,SS)-4,8-diaza-3,6,6,9-tetramethyl-undecane-2,10-dione-bisoxime (HM-PAO), bis(N-ethyl)dithiocarbamate (NEt), and bis(N-ethoxy, N-ethyl)dithiocarbamate (NOEt). One million murine myoblasts were incubated for 30-60 minutes with 5 mCi of each of the 99mTc complexes prepared from the above ligands. Viability was assessed by microscopic counting after trypan blue staining, and the radioactivity absorbed in the cells was measured after centrifugation. The compound with the highest uptake in cellular pellets was [{sup 99m}Tc]N-NOEt. The biodistribution of myoblasts labeled with this complex was evaluated after intraaortic injection in dystrophic mice. Such an approach has the potential of effecting widespread gene transfer through the bloodstream to muscles lacking dystrophin.

  17. Experimental biodistribution studies of 99mTc-recombinant human serum albumin (rHSA): a new generation of radiopharmaceutical

    International Nuclear Information System (INIS)

    Perkins, A.C.; Frier, M.

    1994-01-01

    Recombinant human serum albumin (rHSA) produced by cultured fermentation has been prepared in the form of microcapsules nominally 3-5 μm in diameter and radiolabelled with technetium-99m following reduction with stannous chloride. Radiochemical purity was assessed by chromatography on instant thin-layer chromatography and found to be greater than 90%. No evidence of aggregation was seen by microscopic examination. Imaging biodistribution studies in New Zealand white rabbits demonstrated targeting to the liver or lung, respectively, depending upon the size and surfactant properties of the microcapsules. This communication is the first to show scintigraphic studies using 99m Tc-labelled rHSA with the potential for lung, liver and cardiovascular imaging and demonstrates that recombinant DNA technology offers an important new source of materials suitable for use as radiopharmaceuticals without the need for pooled human blood products. (orig.)

  18. Boron Neutron Capture Therapy (BCNT) for the Treatment of Liver Metastases: Biodistribution Studies of Boron Compounds in an Experimental Model

    Energy Technology Data Exchange (ETDEWEB)

    Marcela A. Garabalino; Andrea Monti Hughes; Ana J. Molinari; Elisa M. Heber; Emiliano C. C. Pozzi; Maria E. Itoiz; Veronica A. Trivillin; Amanda E. Schwint; Jorge E. Cardoso; Lucas L. Colombo; Susana Nievas; David W. Nigg; Romina F. Aromando

    2011-03-01

    Abstract We previously demonstrated the therapeutic efficacy of different boron neutron capture therapy (BNCT) protocols in an experimental model of oral cancer. BNCT is based on the selective accumulation of 10B carriers in a tumor followed by neutron irradiation. Within the context of exploring the potential therapeutic efficacy of BNCT for the treatment of liver metastases, the aim of the present study was to perform boron biodistribution studies in an experimental model of liver metastases in rats. Different boron compounds and administration conditions were assayed to determine which administration protocols would potentially be therapeutically useful in in vivo BNCT studies at the RA-3 nuclear reactor. A total of 70 BDIX rats were inoculated in the liver with syngeneic colon cancer cells DHD/K12/TRb to induce the development of subcapsular tumor nodules. Fourteen days post-inoculation, the animals were used for biodistribution studies. We evaluated a total of 11 administration protocols for the boron compounds boronophenylalanine (BPA) and GB-10 (Na210B10H10), alone or combined at different dose levels and employing different administration routes. Tumor, normal tissue, and blood samples were processed for boron measurement by atomic emission spectroscopy. Six protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue. Boron concentration values in tumor and normal tissues in the liver metastases model show it would be feasible to reach therapeutic BNCT doses in tumor without exceeding radiotolerance in normal tissue at the thermal neutron facility at RA-3.

  19. Study of biodistribution of lipidic nanospheres charged with cis-diaminedichloroplatinum (II) and labelled with radioactive nuclei of Indium-111

    International Nuclear Information System (INIS)

    Lopez R, V.; Juarez O, C.; Medina L, A.; Perez C, E.; Garcia L, P.

    2007-01-01

    The general objective of the study was to evaluate the lipidic nanospheres biodistribution charged with cis-diaminedichloroplatinum (II) (cis-DDP) and labelled with radioactive nuclei of Indium-111 (Lip-Cis-in-111) in Wistar rats and in a tumoral model of CaCu. The conclusions were: 1. The system Lip-Cis-in-111 it presents a very fast elimination probably, to a fast recognition response of the reticuloendothelial system (RES). 2. It is planned to make modifications to the formulation to increase the quantity of the hydrophilic polymer (PEG), so that its time of residence in the blood is bigger and allow a bigger accumulation in the tumor. (Author)

  20. Iodine-123 labelled nor-beta-CIT binds to the serotonin transporter in vivo as assessed by biodistribution studies in rats

    NARCIS (Netherlands)

    Booij, J.; Knol, R. J.; Reneman, L.; de Bruin, K.; Janssen, A. G.; van Royen, E. A.

    1998-01-01

    Iodine-123 labelled 2beta-carbomethoxy-3beta-4-iodophenylnortropane (nor-beta-CIT), a radioiodinated cocaine analogue, was evaluated as an agent for the in vivo labelling of serotonin transporters by biodistribution studies in rats. Intravenous injection of [123I]nor-beta-CIT resulted in high

  1. Synthesis, characterization, and biodistribution studies of {sup 99m}Tc-labeled SBA-16 mesoporous silica nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Branco de Barros, André Luís [Centro de Desenvolvimento da Tecnologia Nuclear, Belo Horizonte, Minas Gerais (Brazil); Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais (Brazil); Silva de Oliveira Ferraz, Karina; Soares Dantas, Thais Cristina; Ferreira Andrade, Gracielle [Centro de Desenvolvimento da Tecnologia Nuclear, Belo Horizonte, Minas Gerais (Brazil); Nascimento Cardoso, Valbert [Faculdade de Farmácia, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais (Brazil); Barros de Sousa, Edésia Martins, E-mail: sousaem@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear, Belo Horizonte, Minas Gerais (Brazil)

    2015-11-01

    Along with anti-cancer drug delivery researches, many efforts have been done to develop new tracers for diagnostic applications. Based on advances in molecular imaging, nanoparticles can be used to visualize, characterize and measure biological process at molecular and cellular level. Therefore, the purpose of this study was to synthesize, characterize and radiolabeled mesoporous silica nanoparticles (MSNs) for in vivo applications. The nanoparticles were synthesized, functionalized with 3-aminopropyltriethoxysilane (APTES) and then, anchored with diethylenetriaminepentaacetic acid (DTPA). Particles were physicochemical characterized by elemental analysis (CHN), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FTIR), and zeta potential, and were morphologically characterized by scanning electron microscopy (SEM), low-angle X-ray diffraction (XRD) and transmission electron microscopy (TEM) techniques. Results indicate that functionalization process was successfully achieved. Next, functionalized silica nanoparticles were radiolabeled with technetium-99m showing high radiochemical yields and high radiolabeled stability. These findings allow the use of the particles for in vivo applications. Biodistribution and scintigraphic images were carried out in healthy mice in order to determine the fate of the particles. Results from in vivo experiments showed high uptake by liver, as expected due to phagocytosis. However, particles also showed a significant uptake in the lungs, indicated by high lung-to-non-target tissue ratio. In summary, taking into account the great potential of these silica mesoporous structures to carry molecules this platform could be a good strategy for theranostic purposes. - Highlights: • Silica mesoporous nanoparticles were successfully prepared. • Functionalization with DTPA was achieved. • High radiolabeled yields and in vitro stability were reached. • Biodistribution and scintigraphic images were performed.

  2. Alteration of 99mTc-DMSA biodistribution in glomerulonephritis

    International Nuclear Information System (INIS)

    Rajic, M.; Bogicevic, M.; Ilic, S.; Vlajkovic, M.; Antic, S.; Mitic, B.; Avramovic, M.; Mitic-Zlatovic, M.; Stefanovic, V.

    2002-01-01

    The aim of this study was to assess the relation between 99T c-DMSA biodistribution and its reliability as a marker of renal function in patients with glomerular kidney diseases. Sixty-seven patients involved in this study were classified into two groups according to 99T c-DTPA clearance and serum creatinine values: the 1. group consisted of 42 patients without renal failure while the 2nd group included 25 patients with renal failure. 99T c-DMSA biodistribution was determined by measuring kidney, blood and urine activity at 2 h and 4 h. The results, compared with those of 23 healthy volunteers, indicated the quantitative alteration of 99T c-DMSA distribution in both glomerulonephritis patient groups. In reference to the control mean values of 2 h and 4 h, in patients without renal failure, kidney activity was found decreased to 52% and 57%, while the blood activity increase of 37% and 44% was recorded together with the urine activity increase of 38% and 23%. In patients with renal failure the alterations of renal and blood activity were more remarkable, but the urine loss was found to be unchanged. It is suggested that these biodistribution changes originate mainly from tubular impairment. However, in glomerulonephritis patients, altered glomerular filtration might considerably affect biodistribution of this radiopharmaceutical and limits its suitability for precise quantitative estimation of renal function. (author)

  3. Biodistribution of Boron compounds in an experimental model of liver metastases for Boron Neutron Capture (BNCT) Studies

    International Nuclear Information System (INIS)

    Garabalino, Marcela A.; Monti Hughes, Andrea; Molinari, Ana J.; Heber, Elisa M.; Pozzi, Emiliano C.C.; Itoiz, Maria E.; Trivillin, Veronica A.; Schwint, Amanda E.; Nievas, Susana; Aromando, Romina F.

    2009-01-01

    Boron Neutron Capture Therapy (BNCT) is a binary treatment modality that involves the selective accumulation of 10 B carriers in tumors followed by irradiation with thermal or epithermal neutrons. The high linear energy transfer alpha particles and recoiling 7 Li nuclei emitted during the capture of a thermal neutron by a 10 B nucleus have a short range and a high biological effectiveness. Thus, BNCT would potentially target neoplastic tissue selectively. In previous studies we demonstrated the therapeutic efficacy of different BNCT protocols in an experimental model of oral cancer. More recently we performed experimental studies in normal rat liver that evidenced the feasibility of treating liver metastases employing a novel BNCT protocol proposed by JEC based on ex-situ treatment and partial liver auto-transplant. The aim of the present study was to perform biodistribution studies with different boron compounds and different administration protocols to determine the protocols that would be therapeutically useful in 'in vivo' BNCT studies at the RA-3 Nuclear Reactor in an experimental model of liver metastases in rats. Materials and Methods. A total of 70 BDIX rats (Charles River Lab., MA, USA) were inoculated in the liver with syngeneic colon cancer cells DH/DK12/TRb (ECACC, UK) to induce the development of subcapsular metastatic nodules. 15 days post-inoculation the animals were used for biodistribution studies. A total of 11 protocols were evaluated employing the boron compounds boronophenylalanine (BPA) and GB-10 (Na 2 10 B 1 -0H 10 ), alone or combined employing different doses and administration routes. Tumor, normal tissue and blood samples were processed for boron measurement by ICP-OES. Results. Several protocols proved potentially useful for BNCT studies in terms of absolute boron concentration in tumor and preferential uptake of boron by tumor tissue, i.e. BPA 15.5 mg 10 B/kg iv + GB-10 50 mg 10 B/kg iv; BPA 46.5 mg 10 B/kg ip; BPA 46.5 mg 10 B/kg ip

  4. Biodistribution study with combined administration of BPA and BSH for BNCT in the hamster cheek pouch oral cancer model

    International Nuclear Information System (INIS)

    Garabalino, M A; Heber, E M; Monti Hughes, A; Pzzi, E C C; Molinari, A J; Niggg, D W; Bauer, W; Trivillin, V A; Schwint, A E

    2012-01-01

    We previously proved the therapeutic potential of the chemically non-selective boron compound decahydrodecaborate (GB-10) as a stand-alone boron carrier for BNCT in the hamster cheek pouch oral cancer model with no toxic effects in normal or precancerous tissue. Although GB-10 is not taken up selectively by oral tumor tissue, selective tumor lethality would result from selective aberrant tumor blood vessel damage. Furthermore, BNCT efficacy was enhanced when GB-10 and boronophenylalanine (BPA) were administered jointly. The fact that sodium mercaptoundecahydro-closo-dodecaborate (BSH) is being investigated clinically as a stand-alone boron agent for BNCT of brain tumors and in combination with BPA for recurrent head and neck malignancies makes it a particularly interesting boron compound to explore. Based on the working hypothesis that BSH would conceivably behave similarly to GB-10 in oral cancer, we previously performed biodistribution studies with BSH alone in the hamster cheek pouch oral cancer model. The aim of the present study was to perform biodistribution studies of BSH + BPA administered jointly in the hamster cheek pouch oral cancer model as a starting point to contribute to the knowledge of (BSH+BPA)-BNCT radiobiology and optimize therapeutic efficacy. The right cheek pouch of Syrian hamsters was subjected to topical administration of a carcinogen twice a week for 12 weeks. Once the exophytic tumors, i.e. squamous cell carcinomas, had developed, the animals were used for biodistribution studies with BSH + BPA. Three administration protocols with different proportions of each of the compounds were assessed: 1. BSH, 50 mg 10 B/kg, iv + BPA, 15.5 mg 10 B/kg, ip; 2. BSH, 34.5 mg 10 B/kg, iv + BPA, 31 mg 10 B/kg, ip; 3. BSH, 20 mg 10 B/kg, iv + BPA, 46.5 mg 10 B/kg, ip. Groups of animals were euthanized 4 h after the administration of BSH and 3 h after the administration of BPA. Samples of blood, tumor, precancerous and normal pouch and other tissues with

  5. Labeling, stability and biodistribution studies of {sup 99m}Tc-cyclized Tyr{sup 3}-octreotate derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Bigott-Hennkens, Heather M. [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Dannoon, Shorouk F.; Noll, Samantha M. [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Ruthengael, Varyanna C. [Research Service, Harry S Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States); Jurisson, Silvia S., E-mail: JurissonS@missouri.ed [Department of Chemistry, University of Missouri, Columbia, MO 65211 (United States); Lewis, Michael R., E-mail: LewisMic@missouri.ed [Department of Veterinary Medicine and Surgery, University of Missouri, Columbia, MO 65211 (United States); Research Service, Harry S Truman Memorial Veterans' Hospital, Columbia, MO 65201 (United States)

    2011-05-15

    Introduction: To probe the interplay between radiotracer stability and somatostatin receptor affinity, Tyr{sup 3}-octreotate and six variations of its peptide sequence, for which the Re-cyclized products were previously reported, were radiolabeled with {sup 99m}Tc and investigated for their in vitro stability. Methods: Radiolabeling of the peptides was effected by ligand exchange from {sup 99m}Tc-glucoheptonate, and the desired products were purified by radio-RP-HPLC. The in vitro stability in phosphate buffered saline, mouse serum and cysteine solutions at physiological temperature and pH for all seven {sup 99m}Tc-cyclized peptides was determined by radio-RP-HPLC and radio-TLC. Normal CF-1 mouse biodistribution studies were performed for three of the {sup 99m}Tc-cyclized peptides. Results: Based on the fully characterized Re-cyclized peptide analogues, four {sup 99m}Tc-coordination motifs were proposed for the {sup 99m}Tc-cyclized peptides. Technetium-99m-cyclized Tyr{sup 3}-octreotate derivatives with N{sub 2}S{sub 2} metal coordination modes and large metal ring sizes were susceptible to oxidation and loss of {sup 99m}Tc in the form of {sup 99m}TcO{sub 4}{sup -}, as evidenced by their instability in the various solutions under physiological conditions (15-58% intact at 24 h). As anticipated, the addition of a third cysteine to the sequence stabilized the {sup 99m}Tc metal coordination, and peptides with NS{sub 3} coordination modes remained >85% intact out to 24 h. No significant differences were observed in the biodistribution studies performed with three peptides of varying stabilities. Conclusions: Improvements in stability were not sufficient to outweigh the low somatostatin receptor affinity for the peptides in this study. Further improvements in the peptide sequence and/or metal coordination are needed to result in a radiodiagnostic/radiotherapeutic pair for targeting the somatostatin receptor.

  6. Design, synthesis, and evaluation of gadolinium cationic lipids as tools for biodistribution studies of gene delivery complexes.

    Science.gov (United States)

    Leclercq, Francoise; Cohen-Ohana, Mirit; Mignet, Nathalie; Sbarbati, Andrea; Herscovici, Jean; Scherman, Daniel; Byk, Gerardo

    2003-01-01

    Gadolinium-chelating cationic lipids have been synthesized to obtain lipoplexes with MRI contrast properties. These compounds were designed to follow the biodistribution of synthetic DNA for gene delivery by nuclear magnetic resonance imaging. The lipid MCO-I-68 was synthesized, and chelate complexes with gadolinium were formed and characterized in terms of physicochemical and DNA binding properties. The transfection activity of MCO-I-68-Gd/DNA complexes was assayed in vitro on NIH 3T3. Different formulations of the product were tested. When up to 5% of the gadolinium lipid complexes were co-formulated with the cationic lipid RPR120535 used as a reference, the transfection levels were maintained as compared to RPR120535 alone. To date, only a liposomal formulation of a gadolinium-cationic lipid chelate without DNA had been observed using magnetic resonance imaging. In vivo intratumoral administration of MCO-I-68-Gd/DNA lipoplexes to tumor model led to an important increase of the NMR signal. It was demonstrated that the new complexes also acted as transfection carriers when they were formulated from liposomes.

  7. In vivo anti-psoriatic activity, biodistribution, sub-acute and sub-chronic toxicity studies of orally administered methotrexate loaded chitin nanogel in comparison with methotrexate tablet.

    Science.gov (United States)

    Panonnummal, Rajitha; Jayakumar, R; Anjaneyan, Gopikrishnan; Sabitha, M

    2018-04-15

    The anti-psoriatic efficacy of orally administered methotrexate loaded chitin nanogel (MCNG) was evaluated (two doses- 2.715 mg/kg and 5.143 mg/kg) and compared against orally administered methotrexate tablet MTX (5.143 mg/kg). MCNG at both dose levels of 2.715 mg/kg and 5.143 mg/kg exhibited significant anti-psoriatic activity which is very much comparable with MTX, caused normalization of histological features and inflammatory score associated with induced psoriasis. Biodistribution studies revealed the presence of drug in serum and in vital organs at all the three cases with highest amount in MCNG at 5.143 mg/kg dose, followed by MTX tablet and are lowest in MCNG at 2.715 mg/kg dose. MCNG at the highest dose of 5.143 mg/kg caused liver, lung and kidney toxicities on sub acute toxicity studies and MTX tablet was found to be toxic on liver and lung on sub chronic toxicity studies. MCNG 2.715 mg/kg was found to be safe on both sub acute and sub chronic administrations, suggesting that it can provide sufficient serum and tissue level of methotrexate necessary to clear psoriatic lesions, without inducing systemic toxicity and expected to be a better alternative for orally administered conventional methotrexate tablet for patients who need systemic medications for psoriasis. Copyright © 2018. Published by Elsevier B.V.

  8. Development of Nanoemulsion Based Gel Loaded with Phytoconstituents for the Treatment of Urinary Tract Infection and in Vivo Biodistribution Studies

    Directory of Open Access Journals (Sweden)

    Atinderpal Kaur

    2017-12-01

    Full Text Available Purpose: A nanoemulsion based gel containing Polyphenon 60 (P60 and cranberry (CRB has been developed to deliver via intravaginal route for the treatment of urinary tract infection. Methods: Polyphenon 60 and cranberry were loaded in a single nanoemulsion gel (NBG by ultra-sonication method and characterized for particle size, rheological properties, in vitro release and growth curve analysis. P60+CRB NBG were radiolabelled using technetium pertechnetate (99mTc to perform in vivo pharmacokinetic studies in animals. Results: The finalized NE had a droplet size of 58±1 nm. In vitro release of 90.92 ± 0.6% in 8 hr for P60 and 99.39 ± 0.5% in 6 hr for CRB was observed in simulated vaginal fluid. Growth curve of E. coli indicated the inhibitory action of nanoemulsion based gel at the fifth hour of inoculation. Gamma scintigraphy studies on female Sprague-Dawley rats showed transport of nanoemulsion based gel from the vaginal cavity into the systemic circulation. Further, biodistribution studies with radiolabelled P60+CRB NBG showed significant higher uptake of radiolabelled actives by kidney (3.20±0.16 and urinary bladder (3.64±0.29, when administered intravaginally. Conclusion: The findings suggested 99mTc-P60+CRB NBG can potentially be transported through vaginal cavity and reach the target organs and showed effective distribution in organs affected in urinary tract infection

  9. Comparison of two methods of quantitation in human studies of biodistribution and radiation dosimetry

    International Nuclear Information System (INIS)

    Smith, T.

    1992-01-01

    A simple method of quantitating organ radioactivity content for dosimetry purposes based on relationships between organ count rate and the initial whole body count rate, has been compared with a more rigorous method of absolute quantitation using a transmission scanning technique. Comparisons were on the basis of organ uptake (% administered activity) and resultant organ radiation doses (mGy MBq -1 ) in 6 normal male volunteers given a 99 Tc m -labelled myocardial perfusion imaging agent intravenously at rest and following exercise. In these studies, estimates of individual organ uptakes by the simple method were in error by between +24 and -16% compared with the more accurate method. However, errors on organ dose values were somewhat less and the effective dose was correct to within 3%. (Author)

  10. Preclinical good laboratory practice-compliant safety study to evaluate biodistribution and tumorigenicity of a cartilage advanced therapy medicinal product (ATMP).

    Science.gov (United States)

    Zscharnack, Matthias; Krause, Christoph; Aust, Gabriela; Thümmler, Christian; Peinemann, Frank; Keller, Thomas; Smink, Jeske J; Holland, Heidrun; Somerson, Jeremy S; Knauer, Jens; Schulz, Ronny M; Lehmann, Jörg

    2015-05-20

    The clinical development of advanced therapy medicinal products (ATMPs), a new class of drugs, requires initial safety studies that deviate from standard non-clinical safety protocols. The study provides a strategy to address the safety aspects of biodistribution and tumorigenicity of ATMPs under good laboratory practice (GLP) conditions avoiding cell product manipulation. Moreover, the strategy was applied on a human ATMP for cartilage repair. The testing strategy addresses biodistribution and tumorigenicity using a multi-step analysis without any cell manipulation to exclude changes of test item characteristics. As a safeguard measurement for meeting regulatory expectations, the project design and goals were discussed continuously with the regulatory authority using a staggered scientific advice concept. Subsequently, the strategy was applied to co.don chondrosphere® (huChon spheroid), a tissue-engineered matrix-free ATMP of human normal chondrocytes. In both the biodistribution and tumorigenicity studies, huChon spheroids were implanted subcutaneously into 40 immunodeficient mice. Biodistribution was studied 1 month after implantation. A skin disc containing the huChon spheroid, two surrounding skin rings and selected organs were analyzed by validated, gender-specific, highly-sensitive triplex qPCR and by immunohistochemistry (IHC). No human DNA was detected in distant skin rings and analyzed organs. IHC revealed no direct or indirect indications of cell migration. Tumorigenicity was assessed 6 months after huChon spheroid implantation by palpation, macroscopic inspection, histology and IHC. No mice from the huChon spheroid group developed a tumor at the implantation site. In two mice, benign tumors were detected that were negative for HLA-ABC, suggesting that they were of spontaneous murine origin. In summary, the presented strategy using a multi-step analysis was confirmed to be suitable for safety studies of ATMPs.

  11. Radiolabeling of substance P with Lutetium-177 and biodistribution study in AR42J pancreatic tumor xenografted Nude mice

    International Nuclear Information System (INIS)

    Araujo, Bortoleti de; Pujatti, Priscilla Brunelli; Barrio, Ofelia; Caldeira, Jose S.; Mengatti, Jair; Suzuki, Miriam F.

    2008-01-01

    Pancreatic tumor (PT) is a neuroendocrine neoplasm that usually origin metastases in the respiratory and gastrointestinal tract. In recent years, new developments in targeted therapies have emerged and the presence of peptide receptors at the cell membrane of PT constitutes the basis of the clinical use of specific radiolabeled ligands. Substance P, an 11-amino acid peptide which has an important role in modulating pain transmission trough neurokinin 1 and 2 receptors (NKr), may play a role in the pathogenesis of PT, because approximately 10% of these tumors over express NKr. The aim of the present work was to produce a pure and stable SP analog (DOTA-SP) radiolabeled with Lutetium-177 ( 177 Lu), and to evaluate its in vivo target to AR42J pancreatic tumor cells in Nude mice in other to verify if SP can be used in this pancreatic tumor detection and treatment. 177 Lu (half-life 6.7 days) has both β and γ-emissions suitable for radiotherapy and imaging respectively. Substance P was successfully labeled with high yield (>99%) at optimized conditions and kept stable for more than 72 hours at 4 deg C and 24 hours in human plasma. Biodistribution studies showed that SP excretion was mainly performed by renal pathway. In addition, 177 Lu-DOTA-SP showed higher uptake by tumor than normal pancreas, indicating the presence of NK receptors in AR42J pancreatic tumor. (author)

  12. Biodistribution study of the anesthetic sodium phenobarbital labelled with technetium-99 in swiss mice infected with Schistosoma mansoni Sambon, 1907

    Energy Technology Data Exchange (ETDEWEB)

    Simoes, Susana Balmant Emerique; Machado Silva, Jose Roberto [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Faculdade de Ciencias Medicas. Dept. de Patologia e Laboratorios; Gutfilen, Bianca; Oliveira, Marcia Betania; Bernardo Filho, Mario [Universidade do Estado, Rio de Janeiro, RJ (Brazil). Inst. de Biologia. Dept. de Biofisica e Biometria; Presgrave, Otavio Augusto Franca [Fundacao Inst. Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, RJ (Brazil). Inst. Nacional de de Controle de Qaulidade em Saude. Dept. de Farmacologia e Toxicologia

    1997-09-01

    Technetium-99 m ({sup 99m} Tc) is a radionuclide that has negligible environmental impact, is easily available, inexpensive and can be used as a radioactive tracer in biological experiences. In order to know the mode of action of sodium phenobarbital in moving adult Schistosoma mansoni worms from mesenteric veins to the liver, we labelled sodium phenobarbital (PBBT) with {sup 99m} Tc and a biodistribution study in infected and non-infected Swiss mice was performed. The PBBT was incubated with stannous chloride used as reducing agent and with {sup 99m} Tc, as sodium pertechnetate. The radioactivity labelling(%) was determined by paper ascending chromatography performed with acetone (solvent). The{sup 99m} Tc-PBBT was administered by intraperitoneal route to Swiss mice infected eight weeks before. The animals were perfused after different periods of time (0,1,2,3,4 hr) when blood, spleen, liver, portal vein, mesenteric veins, stomach, kidneys and adult worms were isolated. The radioactivity present in these samples was counted in a well counter and the percentage was determined. THe radioactivity was mainly taken up by the blood, kidney, liver and spleen. No radioactivity was found on the adult worms. We concluded that the worm shift was due to an action on the host of the sodium phenobarbital. (author) 24 refs., 3 tabs.

  13. Biodistribution study of the anesthetic sodium phenobarbital labelled with technetium-99 in swiss mice infected with Schistosoma mansoni Sambon, 1907

    International Nuclear Information System (INIS)

    Simoes, Susana Balmant Emerique; Machado Silva, Jose Roberto; Gutfilen, Bianca; Oliveira, Marcia Betania; Bernardo Filho, Mario; Presgrave, Otavio Augusto Franca

    1997-01-01

    Technetium-99 m ( 99m Tc) is a radionuclide that has negligible environmental impact, is easily available, inexpensive and can be used as a radioactive tracer in biological experiences. In order to know the mode of action of sodium phenobarbital in moving adult Schistosoma mansoni worms from mesenteric veins to the liver, we labelled sodium phenobarbital (PBBT) with 99m Tc and a biodistribution study in infected and non-infected Swiss mice was performed. The PBBT was incubated with stannous chloride used as reducing agent and with 99m Tc, as sodium pertechnetate. The radioactivity labelling(%) was determined by paper ascending chromatography performed with acetone (solvent). The 99m Tc-PBBT was administered by intraperitoneal route to Swiss mice infected eight weeks before. The animals were perfused after different periods of time (0,1,2,3,4 hr) when blood, spleen, liver, portal vein, mesenteric veins, stomach, kidneys and adult worms were isolated. The radioactivity present in these samples was counted in a well counter and the percentage was determined. THe radioactivity was mainly taken up by the blood, kidney, liver and spleen. No radioactivity was found on the adult worms. We concluded that the worm shift was due to an action on the host of the sodium phenobarbital. (author)

  14. Synthesis and biodistribution study of 3-iodo-4-hydroxyphenyl-cysteamine for detection of malignant melanoma based on specific enzyme of melanin formation

    International Nuclear Information System (INIS)

    Nishii, R.; Nagamachi, S.; Tamura, S.; Kawai, K.; Nishimura, K.; Kinuya, S.; Uehara, T.; Tonami, N.; Arano, Y.

    2002-01-01

    Purpose: The aim of our study is to develop a new radiopharmaceutical labeled with radioiodine for detection and therapy of tumors, which have affinity to a characteristic metabolism in tumor. 3-Iodo-4-hydroxyphenyl-L-cysteine (I- L-PC), which we have reported previously, was found to have an interaction for tyrosinase, an essential and rate-limiting enzyme to melanin biosynthesis. In this study, considering higher affinity for tyrosinase, we synthesized 3-iodo-4-hydroxyphenylcysteamine (I-PCA) that was an amine derivative of I-L-PC and examined biodistribution study in melanoma-bearing mice. Method/Materials: 4-Hydroxyphenylcysteamine (4-PCA) was synthesized and radioiodinated in our laboratory. Synthesis of 4-PCA was confirmed by 1 H-NMR, mass spectrometry and elemental analysis. 125 I-PCA was prepared by conventional chloramine-T method under a no-carrier added condition. 125 I-PCA was purified by Sep-Pak-C-18 cartridge and the labeling efficiency and radiochemical purity were examined by TLC analysis. Biodistribution study of I-PCA was performed using B16 melanoma-bearing C57BL6 mice. The radioactivities of each organ were measured and % injected dose / g wet tissue was determined. Moreover, the tumor-to-blood ratio (T/B ratio) and tumor-to-muscle ratios (T/M ratio) of 125 I-PCA were also evaluated and were compared with 125 I-L-PC, 67 Ga-citrate, 125 I-L-AMT and 123 I-MIBG. Results: Radiosynthesis of 125 I-PCA was carried out conveniently and efficiently within only 15 min. A labeling efficiency of more than 73 % resulted in the labeling of 4-PCA to 125 I-PCA. After the simple Sep-Pak purification, no-carrier added 125 I-PCA with radiochemical purity greater than 90 % was obtained. The biodistribution of 125 I-PCA showed rapid blood clearance, renal excretion and low accumulation in normal tissue, while increase of accumulation in the tumor for 30 min. As a consequence, T/B ratio reached approximately 1.6 ± 0.3 and T/M ratio increased up to 8.7 ± 3.2 at 60

  15. Evaluation of labelling conditions, quality control and biodistribution study of 99mTc-5-aminolevulinic acid (5-ALA). A potential liver imaging agent

    International Nuclear Information System (INIS)

    Kalim Ullah Khan; Mohammad Rafi; Samina Roohi; Rizwana Zahoor; Zafar Iqbal; Mushtaq Ahmad

    2014-01-01

    Labelling of 5-aminolevulinic acid (5-ALA) with 99m Tc was achieved by using SnCl 2 ·2H 2 O as reducing agent. Radiochemical purity and labelling efficiency was determined by instant thin layer chromatography/paper chromatography. Efficiency of labelling was dependent on many parameters such as amount of ligand, reducing agent, pH, and time of incubation. 99m Tc labelled 5-ALA remained stable for 24 h in human serum. Tissue biodistribution of 99m Tc-5-ALA was evaluated in Sprague-Dawley rats. Biodistribution study (% ID/g) in rats revealed that 99m Tc-5-ALA was accumulated significantly in liver, spleen, stomach and intestine after half hour, 4 and 24 h. Significant activity was noted in bladder and urine at 4 h. High liver uptake of 99m Tc-5-ALA makes it a promising liver imaging agent. (author)

  16. Exploration of dopamine transporter and D2 receptors in morphine dependent rats through 125I-β-CTT, 125I-IBZM cerebral autoradiography and the biodistribution study

    International Nuclear Information System (INIS)

    Lin Yansong; Fang Ping; Ding Shiyu; Chen Zhengping; Zhou Xiang; Hu Mingyang; Wang Bocheng; Zhang Manda; Wang Shizhen

    2001-01-01

    Objective: To explore the variation of cerebral dopamine (DA) transmitting system in morphine dependent (MD) rats using dopamine transporter (DAT) and D 2 receptors imaging agent. Methods: MD model rats were established by using a two-compartment (C1 and C2-morphine conditioned compartment) apparatus for assessing morphine conditioned place preferences in rats. 125 I-2β-carbomethoxy-3β-(4-iodophenyl) tropane ( 125 I-β-CIT) and 125 I-3-iodo-2-hydroxy-6-methoxy-N[(1-ethyl-2-pyrrolidinyl) methyl] benzamide ( 125 I-IBZM) cerebral DAT and D 2 receptor autoradiography and biodistribution study were used to evaluate the variation of DAT and D 2 receptors in morphine dependent rats. Results: The mean time of MD rats entering from C1 to C2 was (0.84 +- 0.50) min after 6 days' conditioned place preference training, shorter than that of the control group [(2.40 +- 1.10) min, P 125 I-β-CIT uptake ratio of striatum (ST)/cerebellum (CB) and nucleus acumens (NAC)/CB in MD group were 4.76 +- 0.92 and 2.72 +- 0.96, significantly lower than that of control group (5.92 +- 0.67 and 4.16 +- 0.56, P 125 I-IBZM uptake ratio in MD group were 4.11 +- 0.56 and 2.64 +- 0.25, lower than that in control group (5.43 +- 0.74 and 3.49 +- 0.65, P 125 I-β-CIT, 125 I-IBZM biodistribution study also showed that the DAT and D 2 binding sites were reduced in ST of MD group by (21.68 +- 11.11)% and (18.69 +- 9.97)% comparing to the controls, respectively. Conclusions: The DAT and D 2 receptors in both ST and NAC were all involved and reduced to some extent in morphine dependent model rats, the DAT and D 2 receptor imaging agent could reflect the variation of DAT and D 2 receptors, this would afford the theoretical basis for D 2 receptors and DAT imaging in study on preventing drug addiction and on its abstinence

  17. Biodistribution, pharmacokinetic, and imaging studies with 186Re-labeled NR-LU-10 whole antibody in LS174T colonic tumor-bearing mice

    International Nuclear Information System (INIS)

    Goldrosen, M.H.; Biddle, W.C.; Pancook, J.; Bakshi, S.; Vanderheyden, J.L.; Fritzberg, A.R.; Morgan, A.C. Jr.; Foon, K.A.

    1990-01-01

    Biodistribution, pharmacokinetic, and radioimaging studies were performed with 186Re-labeled NR-LU-10 whole antibody in athymic nude mice bearing the LS174T tumor growing either s.c. or in an experimental hepatic metastasis model. NR-LU-10 is an IgG2b murine monoclonal antibody (MAb) that reacts with virtually all human tumors of epithelial origin. NR-BC-1, a IgG2b murine MAb that reacts with normal human B-cell and B malignancies, was used as an isotype-matched control. These MAbs were radiolabeled with 186Re by a preformed chelate approach by using the triamide thiolate ligand system. 186Re-labeled NR-LU-10 (50 microCi) was injected into nude mice bearing LS174T tumors growing s.c. Biodistribution studies revealed that the LS174T tumor retained the highest concentration of 186Re-labeled NR-LU-10 at day 6. The tumor:blood ratio ranged from 0.1:1 to 10.8:1 by day 6, the last day of analysis. In contrast the tumor:blood ratio of 186Re-labeled NR-BC-1, the isotype-matched MAb control, was 1:1 on day 6. Pharmacokinetic analysis indicated that the t1/2 beta of NR-LU-10 for blood and other tissues ranged from 21 to 25 h, while the t1/2 beta for the LS174T tumor averaged 52 h. The area under the curve for tumor compared to blood was 2.8- to 5.7-fold higher than the area under the curve for all other tissues and organs. The mean residence time for NR-LU-10 in blood and all other organs ranged from 23 to 26 h, while the mean residence time for NR-LU-10 in the LS174T tumor was 72 h. Scintigraphic images revealed selective uptake of the 186Re-labeled NR-LU-10, but not of the 186Re-labeled NR-BC-1, at the LS174T tumor site. Studies in an experimental model of hepatic metastasis revealed a similar selective pattern of 186Re-labeled NR-LU-10 accumulation. Scintigraphic images of the LS174T tumor growing within the athymic nude mouse liver were obtained

  18. Fluorescent nanoparticles present in Coca-Cola and Pepsi-Cola: physiochemical properties, cytotoxicity, biodistribution and digestion studies.

    Science.gov (United States)

    Li, Shen; Jiang, Chengkun; Wang, Haitao; Cong, Shuang; Tan, Mingqian

    2018-02-01

    Foodborne nanoparticles (NPs) have drawn great attention due to human health concerns. This study reports the detection of the presence of fluorescent NPs, about 5 nm, in two of the most popular beverages, Coca-Cola (Coke) and Pepsi-Cola (Pepsi). The NPs contain H, C and O, three elements with a tunable emission and with a quantum yield of 3.3 and 4.3% for Coke and Pepsi, respectively. The presence of sp 3 -hybridized carbon atoms of alcohols and ethers bonds was confirmed by NMR analysis. The NPs can be taken up by living cells and accumulate within cell membrane and cytoplasm. Evaluation of the acute toxicity of the NPs revealed that the BALB/c mice appeared healthy after administration of a single dose of 2 g kg -1 body weight. Analysis of glutamate pyruvate transaminase (GPT), glutamic oxaloacetic transaminase (GOT), urea and creatinine showed that there were statistically, but not biologically, significant differences in some of these biochemical parameters between the test and control groups. No obvious organ damage or apparent histopathological abnormality was observed in the tested mice. The biodistribution study in major organs indicated that the NPs were easily accumulated in the digestive tract, and they were able to cross the blood-brain barrier and dispersed in the brain. In vitro digestion of the NPs showed a significant fluorescence quenching of the NPs. This work represents the first report of foodborne fluorescent NPs present in Coke and Pepsi, and provides valuable insights into physicochemical properties of these NPs and their toxicity characteristics both in vitro and in vivo.

  19. Preclinical Study of 68Ga-DOTATOC: Biodistribution Assessment in Syrian Rats and Evaluation of Absorbed Dose in Human Organs.

    Science.gov (United States)

    Naderi, Mojdeh; Zolghadri, Samaneh; Yousefnia, Hassan; Ramazani, Ali; Jalilian, Amir Reza

    2016-01-01

    Gallium-68 DOTA-DPhe 1 -Tyr 3 -Octreotide ( 68 Ga-DOTATOC) has been applied by several European centers for the treatment of a variety of human malignancies. Nevertheless, definitive dosimetric data are yet unavailable. According to the Society of Nuclear Medicine and Molecular Imaging, researchers are investigating the safety and efficacy of this radiotracer to meet Food and Drug Administration requirements. The aim of this study was to introduce the optimized procedure for 68 Ga-DOTATOC preparation, using a novel germanium-68 ( 68 Ge)/ 68 Ga generator in Iran and evaluate the absorbed doses in numerous organs with high accuracy. The optimized conditions for preparing the radiolabeled complex were determined via several experiments by changing the ligand concentration, pH, temperature and incubation time. Radiochemical purity of the complex was assessed, using high-performance liquid chromatography and instant thin-layer chromatography. The absorbed dose of human organs was evaluated, based on biodistribution studies on Syrian rats via Radiation Absorbed Dose Assessment Resource Method. 68 Ga-DOTATOC was prepared with radiochemical purity of >98% and specific activity of 39.6 MBq/nmol. The complex demonstrated great stability at room temperature and in human serum at 37°C at least two hours after preparation. Significant uptake was observed in somatostatin receptor-positive tissues such as pancreatic and adrenal tissues (12.83 %ID/g and 0.91 %ID/g, respectively). Dose estimations in human organs showed that the pancreas, kidneys and adrenal glands received the maximum absorbed doses (0.105, 0.074 and 0.010 mGy/MBq, respectively). Also, the effective absorbed dose was estimated at 0.026 mSv/MBq for 68 Ga-DOTATOC. The obtained results showed that 68 Ga-DOTATOC can be considered as an effective agent for clinical PET imaging in Iran.

  20. Comprehensive characterizations of nanoparticle biodistribution following systemic injection in mice

    Science.gov (United States)

    Liao, Wei-Yin; Li, Hui-Jing; Chang, Ming-Yao; Tang, Alan C. L.; Hoffman, Allan S.; Hsieh, Patrick C. H.

    2013-10-01

    Various nanoparticle (NP) properties such as shape and surface charge have been studied in an attempt to enhance the efficacy of NPs in biomedical applications. When trying to undermine the precise biodistribution of NPs within the target organs, the analytical method becomes the determining factor in measuring the precise quantity of distributed NPs. High performance liquid chromatography (HPLC) represents a more powerful tool in quantifying NP biodistribution compared to conventional analytical methods such as an in vivo imaging system (IVIS). This, in part, is due to better curve linearity offered by HPLC than IVIS. Furthermore, HPLC enables us to fully analyze each gram of NPs present in the organs without compromising the signals and the depth-related sensitivity as is the case in IVIS measurements. In addition, we found that changing physiological conditions improved large NP (200-500 nm) distribution in brain tissue. These results reveal the importance of selecting analytic tools and physiological environment when characterizing NP biodistribution for future nanoscale toxicology, therapeutics and diagnostics.Various nanoparticle (NP) properties such as shape and surface charge have been studied in an attempt to enhance the efficacy of NPs in biomedical applications. When trying to undermine the precise biodistribution of NPs within the target organs, the analytical method becomes the determining factor in measuring the precise quantity of distributed NPs. High performance liquid chromatography (HPLC) represents a more powerful tool in quantifying NP biodistribution compared to conventional analytical methods such as an in vivo imaging system (IVIS). This, in part, is due to better curve linearity offered by HPLC than IVIS. Furthermore, HPLC enables us to fully analyze each gram of NPs present in the organs without compromising the signals and the depth-related sensitivity as is the case in IVIS measurements. In addition, we found that changing physiological

  1. Biodistribution and radiation dosimetry of [18F]-5-fluorouracil

    International Nuclear Information System (INIS)

    Hino-Shishikura, Ayako; Suzuki, Akiko; Minamimoto, Ryogo; Shizukuishi, Kazuya; Oka, Takashi; Tateishi, Ukihide; Sugae, Sadatoshi; Ichikawa, Yasushi; Horiuchi, Choichi; Inoue, Tomio

    2013-01-01

    Purpose: To estimate the radiation dose and biodistribution of 18 F-5-fluorouracil ([ 18 F]-5-FU) from positron emission tomography/computed tomography (PET/CT) data, and to extrapolate mouse data to human data in order to evaluate cross-species consistency. Methods: Fifteen cancer patients (head and neck cancer (n=11), colon cancer (n=4)) were enrolled. Sequential PET/CT images were acquired for 2 h after intravenous administration of [ 18 F]-5-FU, and the percent of the injected dose delivered to each organ was derived. For comparison, [ 18 F]-5-FU was administered to female BALB/cAJcl-nu/nu nude mice (n=19), and the percent of the injected dose delivered to mouse organs was extrapolated to the human model. Absorbed radiation dose was calculated using OLINDA/EXM 1.0 software. Results: In human subjects, high [ 18 F]-5-FU uptake was seen in the liver, gallbladder and kidneys. The absorbed dose was highest in the gallbladder wall. In mice, the biodistribution of [ 18 F]-5-FU corresponded to that of humans. Estimated absorbed radiation doses for all organs were moderately correlated, and doses to organs (except the gallbladder and urinary bladder) were significantly correlated between mice and humans. The mean effective [ 18 F]-5-FU dose was higher in humans (0.0124 mSv/MBq) than in mice (0.0058 mSv/MBq). Conclusion: Biodistribution and radiation dosimetry of [ 18 F]-5-FU were compared between humans and mice: biodistribution in mice and humans was similar. Data from mice underestimated the effective dose in humans, suggesting that clinical measurements are needed for more detailed dose estimation in order to ensure radiation safety. The observed effective doses suggest the feasibility of [ 18 F]-5-FU PET/CT for human studies. - Highlights: ► The radiation dose and biodistribution of [ 18 F]-5-FU were estimated from mouse and human data. ► The biodistribution of [ 18 F]-5-FU of mouse and human was corresponded. ► Estimated absorbed radiation doses for organs

  2. Comparison of therapeutic efficacy and biodistribution of 213Bi- and 211At-labeled monoclonal antibody MX35 in an ovarian cancer model

    DEFF Research Database (Denmark)

    Gustafsson, Anna M E; Bäck, Tom; Elgqvist, Jörgen

    2012-01-01

    The purpose of this study was to compare the therapeutic efficacy and biodistribution of the monoclonal antibody MX35 labeled with either (213)Bi or (211)At, both α-emitters, in an ovarian cancer model.......The purpose of this study was to compare the therapeutic efficacy and biodistribution of the monoclonal antibody MX35 labeled with either (213)Bi or (211)At, both α-emitters, in an ovarian cancer model....

  3. Biodistribution of [11C] methylaminoisobutyric acid, a tracer for PET studies on system A amino acid transport in vivo

    International Nuclear Information System (INIS)

    Sutinen, E.; Jyrkkioe, S.; Groenroos, T.; Haaparanta, M.; Lehikoinen, P.; Naagren, K.

    2001-01-01

    [N-methyl- 11 C]α-Methylaminoisobutyric acid ( 11 C-MeAIB) is a potentially useful tracer for positron emission tomography (PET) studies on hormonally regulated system A amino acid transport. 11 C-MeAIB is a metabolically stable amino acid analogue specific for system A amino acid transport. We evaluated the biodistribution of 11 C-MeAIB in rats and humans to estimate the usefulness of the tracer for in vivo human PET studies, for example, on regulation of system A amino acid transport and on tumour imaging. Healthy Sprague-Dawley rats (n=14) were killed 5, 20, 40 or 60 min after the injection of 11 C-MeAIB, and the tissue samples were weighed and counted for 11 C radioactivity. Ten lymphoma patients with relatively limited tumour burden underwent whole-body (WB) PET imaging with 11 C-MeAIB. In addition, three other patients had dynamic PET scanning of the head and neck area, and the tracer uptake was quantitated by calculating the kinetic influx constants (K i values) for the tracer. In animal studies, the highest activity was detected in the kidney, pancreas, adrenal gland and intestines. In humans, the highest activity was found in the salivary glands, and after that in the kidney and pancreas, similar to the results in animal studies. Rapid uptake was also detected in the skeletal muscle. In the graphical analysis, linear plots were obtained, and the mean fractional tracer uptake values (K i ) of the parotid glands (n=3) and cervical muscles (n=3) were 0.039±0.008 min -1 and 0.013±0.006 min -1 , respectively. The K i value of the tumour (n=1) was 0.064 min -1 . Higher uptake of 11 C-MeAIB into the tumour tissue was encountered. These results encourage further 11 C-MeAIB PET studies in humans on the physiology and pathology of system A amino acid transport and on tumour detection. (orig.)

  4. Radiosynthesis of 123I-labeled hesperetin for biodistribution study of orally administered hesperetin

    International Nuclear Information System (INIS)

    Jongho Jeon; So-Young Ma; Dae Seong Choi; Beom-Su Jang; Jung Ae Kang; You Ree Nam; Seonhye Yoon; Sang Hyun Park; Korea University of Science and Technology, Daejeon

    2015-01-01

    The purpose of this study is to synthesize 123 I-labeled hesperetin and to investigate its in vivo behavior. The optimized labeling condition provided two isomers of 123 I-labeled hesperetin with high radiochemical yields and radiochemical purities. Both 123 I-labeled products were orally administered to normal ICR mice, and the initial result showed that most of 123 I activity was detected in the stomach and the intestines. A part of 123 I-labeled hesperetin was absorbed from the small intestine to bloodstream and then it was distributed in normal organs. The results in the present study provided an efficient radiolabeling method of flavonoid and quantitative organ distribution of orally administered hesperetin. (author)

  5. Preclinical safety, pharmacokinetics, pharmacodynamics, and biodistribution studies with Ad35K++ protein: a novel rituximab cotherapeutic

    Directory of Open Access Journals (Sweden)

    Maximilian Richter

    2016-01-01

    Full Text Available Rituximab is a mouse/human chimeric monoclonal antibody targeted toward CD20. It is efficient as first-line therapy of CD20-positive B-cell malignancies. However, a large fraction of treated patients relapse with rituximab-resistant disease. So far, only modest progress has been made in treatment options for rituximab refractory patients. One of the mechanisms for rituximab resistance involves the upregulation of CD46, which is a key cell surface protein that blocks the activation of complement. We have recently developed a technology that depletes CD46 from the cell surface and thereby sensitizes tumor cells to complement-dependent cytotoxicity. This technology is based on a small recombinant protein, Ad35K++ that binds with high affinity to CD46. In preliminary studies using a 6 × histidinyl tagged protein, we had demonstrated that intravenous Ad35K++ injection in combination with rituximab was safe and increased rituximab-mediated killing of CD20-positive target cells in mice and nonhuman primates (NHPs. The presence of the tag, while allowing for easy purification by Ni-NTA chromatography, has the potential to increase the immunogenicity of the recombinant protein. For clinical application, we therefore developed an Ad35K++ protein without His-tag. In the present study, we performed preclinical studies in two animal species (mice and NHPs with this protein demonstrating its safety and efficacy. These studies estimated the Ad35K++ dose range and treatment regimen to be used in patients. Furthermore, we showed that intravenous Ad35K++ injection triggers the shedding of the CD46 extracellular domain in xenograft mouse tumor models and in macaques. Shed serum CD46 can be measured in the serum and can potentially be used as a pharmacodynamic marker for monitoring Ad35K++ activity in patient undergoing treatment with this agent. These studies create the basis for an investigational new drug application for the use of Ad35K++ in combination with

  6. Studies on the Th biodistribution in internal contamination by the fission track method using animals

    International Nuclear Information System (INIS)

    Ciubotariu, M.; Danis, A.; Dumitrescu, G.; Cucu, M.

    1998-01-01

    In our previous studies on the U internal contamination, qualitative and quantitative results were obtained by using the fission track methods. In order to obtain complete data on the fissionable element internal contamination using animals, we started a similar study using Th as contaminating element and Wistar London breed rats as laboratory animals. Different ways to obtain internal contaminations were investigated: ingestion, inhalation, absorption by skin and through wounds. In this stage, Wistar-London breed rats of the same sex, weight and age were internal contaminated by 1 ml Th solution ingestion for each rat corresponding to an Annual Limit Intake.The animals were kept in normal life conditions and under permanent medical surveillance up to their sacrifice. Also, their evacuations where sampled every 24 hours. They were sacrificed at different time intervals after their contamination: 2 days (RAT 1), 7 days (RAT 2) and 14 days (RAT 3). After sacrifice, their vital organs were sampled, weighed, calcined, reweighed and finally analysed by track detection using the fission track micromapping technique. This technique was used in the following conditions: - mica-muscovite as track detector pre-etched for fossil tracks 18 h in HF; - the neutron irradiations were performed in the nuclear reactor VVR-S Bucharest at the neutron fluences of 3x10 15 - 2x10 16 fast neutrons/cm 2 . In order to check whether there is any U contribution to the fission track densities obtained in track detectors, U existing in the rat body due to food and water, the neutron irradiations of the ensembles were performed with and without 1 mm Cd shielding; - the visualization of the Th induced fission tracks were obtained by chemical etching in HF, 3 h at room temperature; - the Th track micromappings obtained in track detectors were studied by optical microscopy using a stereomicroscope WILD M7S for ensemble study (X6-X31) and a binocular ZEISS JENA microscope for qualitative and

  7. In vitro radio autographic studies of the biodistribution of radiopharmaceuticals on blood elements

    International Nuclear Information System (INIS)

    Eipoll-Hamer, E.; De Paula, E.F.; Freitas, L.C.; Pereira, M.J.S.; Carvalho, J.J.; Porto, L.C.M.S.; Fonseca, L.M.; Gutfilen, B.; Bernardo Filho, M.

    1998-01-01

    In the present study we evaluated the binding of the radiopharmaceuticals sodium pertechnetate (Na 99m Tc O 4 ), methylene-diphosphonic acid ( 99m Tc-M D P) and glucoheptonate acid ( 99m Tc-G H A) to blood elements using centrifugation and radio autographic techniques. Heparinized blood was incubated with the labelled compounds for 0,1,2,3,4, 6 and 24 h. Plasma (P) and blood cells (B C) were isolated and precipitated with 5% trichloroacetic acid (TCA), and soluble (S F) and insoluble fractions (IF) were separated. Blood samples were prepared (0 and 24 h) and coated with Lm-1 radio autographic emulsions and percent radioactivity (%rad) in P and B C was determined. The binding of Na 99m Tc O 4 (5 rad) to P was 61.2 (0 h) and 46.0% (24 h), and radioautography showed 63.7% (0 h) and 43.3% (24 h). The binding to B C was 38.8% (0 h) and 54.0% (24 h), and radioautography showed 36.3% (0 h) and 56.7% (24 h). 99m Tc-M D P study presented 91.1% (0 h) to P and 87.2%(24 h), and radioautography showed presented 91.1% (0 h) to P and 87.2% (24 h), and radioautography showed 67.9% (0 h) and 67.4% (24 h). The binding to B C was 8.9% (0 h) and 12.8% (24 h), and radioautography showed 32.1% (0 h) and 32.6% (24 h). 99m Tc-G H A study was 90.1% (0 h) to P and 79.9% (24 h), and radioautography showed 67.2% (0 h) and 60.1% (24 h). The binding to B C was 9.9% (0 h) and 20.1% (24 h), and radioautography showed 32.8% (0 h) and 39.9% (24 h). The comparison of the obtained results suggests that the binding to plasma and blood cells in the two techniques used (radioautography and centrifugation) is qualitatively in accordance. (author)

  8. In vitro radioautographic studies of the biodistribution of radiopharmaceuticals on blood elements

    Directory of Open Access Journals (Sweden)

    Ripoll-Hamer E.

    1998-01-01

    Full Text Available In the present study we evaluated the binding of the radiopharmaceuticals sodium pertechnetate (Na 99mTcO4, methylenediphosphonic acid (99mTc-MDP and glucoheptonate acid (99mTc-GHA to blood elements using centrifugation and radioautographic techniques. Heparinized blood was incubated with the labelled compounds for 0, 1, 2, 3, 4, 6 and 24 h. Plasma (P and blood cells (BC were isolated and precipitated with 5% trichloroacetic acid (TCA, and soluble (SF and insoluble fractions (IF were separated. Blood samples were prepared (0 and 24 h and coated with LM-1 radioautographic emulsions and percent radioactivity (%rad in P and BC was determined. The binding of Na 99mTcO4 (%rad to P was 61.2% (0 h and 46.0% (24 h, and radioautography showed 63.7% (0 h and 43.3% (24 h. The binding to BC was 38.8% (0 h and 54.0% (24 h, and radioautography showed 36.3% (0 h and 56.7% (24 h. 99mTc-MDP study presented 91.1% (0 h to P and 87.2% (24 h, and radioautography showed 67.9% (0 h and 67.4% (24 h. The binding to BC was 8.9% (0 h and 12.8% (24 h, and radioautography showed 32.1% (0 h and 32.6% (24 h. 99mTc-GHA study was 90.1% (0 h to P and 79.9% (24 h, and radioautography showed 67.2% (0 h and 60.1% (24 h. The binding to BC was 9.9% (0 h and 20.1% (24 h, and radioautography showed 32.8% (0 h and 39.9% (24 h. The comparison of the obtained results suggests that the binding to plasma and blood cells in the two techniques used (radioautography and centrifugation is qualitatively in accordance

  9. Biodistribution study of carbogenic dots in cells and in vivo for optical imaging

    International Nuclear Information System (INIS)

    Li Nan; Liang Xiaofei; Wang Lili; Li Zonghai; Li Peiyong; Zhu Yihua; Song Jing

    2012-01-01

    Blue fluorescent carbon dots (C-dots) were synthesized and evaluated for their cytotoxicity and also for their optical imaging performance. The results showed that the C-dots could enter into the Hela cells in 15 min incubation and the uptake increased rapidly from 15 min to 2 h. In cytotoxicity study, C-dots were biocompatible and nontoxic to three human cells including two cancer cells (Hela and SMCC-7721) and one normal cell (HEK 293) in concentrations up to 500 μg/mL. Since the endocytic interference factors, including NaN 3 , MβCD, sucrose, and low temperature, could not play an inhibitory effect on C-dots entering into cells, the direct nonendocytic pathway for C-dots was speculated. The C-dots showed encouraging cell-imaging applications in vitro and in vivo. They entered into cells without any further functionalization, and the fluorescence property of these particles can be used for fluorescence-based cell-imaging applications.

  10. Study of {sup 99m}Tc-DMSA biodistribution in experimental animals

    Energy Technology Data Exchange (ETDEWEB)

    Castro, Thais O.M. de; Silva, Natanael G. da; Colturato, Maria T.; Felgueiras, Carlos F.; Mengatti, Jair; Fukumori, Neuza T.O.; Matsuda, Margareth M.N.; Araújo, Elaine B. de, E-mail: thais.castrom@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Radiofarmacia

    2017-11-01

    {sup 99m}Tc-DMSA, succimer ({sup 99m}Tc), is a radiopharmaceutical commonly used in nuclear medicine for renal function evaluation by imaging. In order to achieve adequate labeling of the product with good radiochemical yield and standardized biological distribution, the interval of 185 - 3700 MBq should be kept in a maximum volume of 3 mL for product labeling. Moreover, one should avoid exposing the reconstituted solution to oxygen and using the product after four hours post labeling. The aim of the study was to quantify and evaluate the influence of different DMSA complexes on biological distribution of the radiopharmaceutical in experimental animals, taking in account variations in the labeling parameters. Radiochemical purity was determined by paper and thin layer chromatography using both acetone/Whatman 3MM, 0.9% NaCl/TLC-SG and n-propanol/ H{sub 2}O/acetic acid (4:3:1 V/V/V)/TLC-SG systems respectively for quantification of {sup 99m}TcO{sub 4} - and {sup 99m}TcO{sub 2} plus some {sup 99m}Tc-DMSA complexes. The labeling activity did not significantly affect the extent of the main complex generation. The presence of oxygen and the concentration of {sup 99}Tc did not markedly change the percentage of the radiochemical impurities in the preparation. Radiochemical purity tests of the DMSA-{sup 99m}Tc based on IPEN-CNEN DMSA-TEC reagent and on another producer's reagent showed similar results. Although the routine method used by IPEN-CNEN to determine the radiochemical yield of {sup 99m}Tc-DMSA was not able to discriminate among {sup 99m}Tc-DMSA complexes, the renal uptake and the kidney to liver plus spleen uptake ratio in rats met the official compendia criteria for the radiopharmaceutical. (author)

  11. Study of "9"9"mTc-DMSA biodistribution in experimental animals

    International Nuclear Information System (INIS)

    Castro, Thais O.M. de; Silva, Natanael G. da; Colturato, Maria T.; Felgueiras, Carlos F.; Mengatti, Jair; Fukumori, Neuza T.O.; Matsuda, Margareth M.N.; Araújo, Elaine B. de

    2017-01-01

    "9"9"mTc-DMSA, succimer ("9"9"mTc), is a radiopharmaceutical commonly used in nuclear medicine for renal function evaluation by imaging. In order to achieve adequate labeling of the product with good radiochemical yield and standardized biological distribution, the interval of 185 - 3700 MBq should be kept in a maximum volume of 3 mL for product labeling. Moreover, one should avoid exposing the reconstituted solution to oxygen and using the product after four hours post labeling. The aim of the study was to quantify and evaluate the influence of different DMSA complexes on biological distribution of the radiopharmaceutical in experimental animals, taking in account variations in the labeling parameters. Radiochemical purity was determined by paper and thin layer chromatography using both acetone/Whatman 3MM, 0.9% NaCl/TLC-SG and n-propanol/ H_2O/acetic acid (4:3:1 V/V/V)/TLC-SG systems respectively for quantification of "9"9"mTcO_4 - and "9"9"mTcO_2 plus some "9"9"mTc-DMSA complexes. The labeling activity did not significantly affect the extent of the main complex generation. The presence of oxygen and the concentration of "9"9Tc did not markedly change the percentage of the radiochemical impurities in the preparation. Radiochemical purity tests of the DMSA-"9"9"mTc based on IPEN-CNEN DMSA-TEC reagent and on another producer's reagent showed similar results. Although the routine method used by IPEN-CNEN to determine the radiochemical yield of "9"9"mTc-DMSA was not able to discriminate among "9"9"mTc-DMSA complexes, the renal uptake and the kidney to liver plus spleen uptake ratio in rats met the official compendia criteria for the radiopharmaceutical. (author)

  12. Quantum dots in axillary lymph node mapping: Biodistribution study in healthy mice

    Directory of Open Access Journals (Sweden)

    Guillemin François

    2008-04-01

    Full Text Available Abstract Background Breast cancer is the first cause of cancer death among women and its incidence doubled in the last two decades. Several approaches for the treatment of these cancers have been developed. The axillary lymph node dissection (ALND leads to numerous morbidity complications and is now advantageously replaced by the dissection and the biopsy of the sentinel lymph node. Although this approach has strong advantages, it has its own limitations which are manipulation of radioactive products and possible anaphylactic reactions to the dye. As recently proposed, these limitations could in principle be by-passed if semiconductor nanoparticles (quantum dots or QDs were used as fluorescent contrast agents for the in vivo imaging of SLN. QDs are fluorescent nanoparticles with unique optical properties like strong resistance to photobleaching, size dependent emission wavelength, large molar extinction coefficient, and good quantum yield. Methods CdSe/ZnS core/shell QDs emitting around 655 nm were used in our studies. 20 μL of 1 μM (20 pmol QDs solution were injected subcutaneously in the anterior paw of healthy nude mice and the axillary lymph node (ALN was identified visually after injection of a blue dye. In vivo fluorescence spectroscopy was performed on ALN before the mice were sacrificed at 5, 15, 30, 60 min and 24 h after QDs injection. ALN and all other organs were removed, cryosectioned and observed in fluorescence microscopy. The organs were then chemically made soluble to extract QDs. Plasmatic, urinary and fecal fluorescence levels were measured. Results QDs were detected in ALN as soon as 5 min and up to 24 h after the injection. The maximum amount of QDs in the ALN was detected 60 min after the injection and corresponds to 2.42% of the injected dose. Most of the injected QDs remained at the injection site. No QDs were detected in other tissues, plasma, urine and feces. Conclusion Effective and rapid (few minutes detection of

  13. Radiohalogenation of biomolecules. An experimental study on radiohalogen preparation, precursor synthesis, radiolabeling and biodistribution

    International Nuclear Information System (INIS)

    Koziorowski, J.

    1998-01-01

    Radiohalogens are widely used in nuclear medicine, both as tool for diagnostic in vivo imaging, and in radionuclide therapy. This study deals with the use of radiohalogens; separation, precursor synthesis, labeling and biological behavior. The focus is on 211 At and 124 I, the former being a candidate for nuclide therapy and the latter potentially useful for diagnostic imaging and Auger-electron based radiotherapy. For astatine the separation, labeling and some biological behavior is described, and for iodine the latter two. Astatine was separated from an irradiated bismuth target by dry distillation. A novel cryotrap was developed for the isolation of astatine and subsequent synthesis of radiolabeled compounds. 5-[ 211 At]astato-2'-deoxyuridine (AUdR) and N-succinimidyl-4-[ 211 At]astatobenzoate (SAB) were synthesized in 95% respectively 90% radiochemical yields. The former is incorporated into DNA of proliferating cells and can therefore be used as an endoradiotherapeutic agent. The latter is a conjugate for the astatination of proteins. Human epidermal growth factor (hEGF) was tagged with astatine using three approaches: a) direct labeling of native hEGF, b) conjugation with SAB, and c) direct labeling of an hEGF - 7-(3-aminopropyl)-7,8-dicarba-nido-undecaborate(1-) conjugate. The overall labeling yields were 3.5% for direct labeling, 44% for SAB and 70% for the hEGF-nido-carborane conjugate. A new route to N-succinimidyl 3- and 4- [ 124 I]iodobenzoate, two reagents for radioiodination of proteins is described affording 90% radiochemical yield. Three radioiodinated analogs of PK11195, 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)isoquinoline-3-carboxyam ide, a peripheral-type benzodiazepine receptor antagonist, were synthesized. All three analogs were obtained in >90% radiochemical yield. Synthesis and application of 5-[ 124 I]iodo-2'-deoxyuridine (IUdR) is presented. The closo-dodecaborate anion was evaluated as prosthetic group for radioiodination of

  14. Quantum dots in axillary lymph node mapping: Biodistribution study in healthy mice

    International Nuclear Information System (INIS)

    Robe, Anne; Pic, Emilie; Lassalle, Henri-Pierre; Bezdetnaya, Lina; Guillemin, François; Marchal, Frédéric

    2008-01-01

    Breast cancer is the first cause of cancer death among women and its incidence doubled in the last two decades. Several approaches for the treatment of these cancers have been developed. The axillary lymph node dissection (ALND) leads to numerous morbidity complications and is now advantageously replaced by the dissection and the biopsy of the sentinel lymph node. Although this approach has strong advantages, it has its own limitations which are manipulation of radioactive products and possible anaphylactic reactions to the dye. As recently proposed, these limitations could in principle be by-passed if semiconductor nanoparticles (quantum dots or QDs) were used as fluorescent contrast agents for the in vivo imaging of SLN. QDs are fluorescent nanoparticles with unique optical properties like strong resistance to photobleaching, size dependent emission wavelength, large molar extinction coefficient, and good quantum yield. CdSe/ZnS core/shell QDs emitting around 655 nm were used in our studies. 20 μL of 1 μM (20 pmol) QDs solution were injected subcutaneously in the anterior paw of healthy nude mice and the axillary lymph node (ALN) was identified visually after injection of a blue dye. In vivo fluorescence spectroscopy was performed on ALN before the mice were sacrificed at 5, 15, 30, 60 min and 24 h after QDs injection. ALN and all other organs were removed, cryosectioned and observed in fluorescence microscopy. The organs were then chemically made soluble to extract QDs. Plasmatic, urinary and fecal fluorescence levels were measured. QDs were detected in ALN as soon as 5 min and up to 24 h after the injection. The maximum amount of QDs in the ALN was detected 60 min after the injection and corresponds to 2.42% of the injected dose. Most of the injected QDs remained at the injection site. No QDs were detected in other tissues, plasma, urine and feces. Effective and rapid (few minutes) detection of sentinel lymph node using fluorescent imaging of quantum dots was

  15. Liposome-encapsulated EF24-HPβCD inclusion complex: a preformulation study and biodistribution in a rat model

    International Nuclear Information System (INIS)

    Agashe, H.; Lagisetty, P.; Sahoo, K.; Bourne, D.; Grady, B.; Awasthi, V.

    2011-01-01

    3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a “drug-in-CD-in liposome” approach. An aqueous solution of EF24 and hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze–thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HPβCD mixture provided k 1:1 value of 9.9 M −1 . The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HPβCD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 ± 2.6 nm) by dehydration–rehydration technique. With extrusion technique, the size of 177 ± 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 μM dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an α-t 1/2 of 21.4 min and β-t 1/2 of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using “drug-in-CD-in liposome” approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution.

  16. Liposome-encapsulated EF24-HPβCD inclusion complex: a preformulation study and biodistribution in a rat model

    Science.gov (United States)

    Agashe, H.; Lagisetty, P.; Sahoo, K.; Bourne, D.; Grady, B.; Awasthi, V.

    2011-06-01

    3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a "drug-in-CD-in liposome" approach. An aqueous solution of EF24 and hydroxypropyl-β-cyclodextrin (HPβCD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze-thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HPβCD mixture provided k 1:1 value of 9.9 M-1. The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HPβCD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 ± 2.6 nm) by dehydration-rehydration technique. With extrusion technique, the size of 177 ± 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 μM dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an α- t 1/2 of 21.4 min and β- t 1/2 of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using "drug-in-CD-in liposome" approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution.

  17. Liposome-encapsulated EF24-HP{beta}CD inclusion complex: a preformulation study and biodistribution in a rat model

    Energy Technology Data Exchange (ETDEWEB)

    Agashe, H; Lagisetty, P; Sahoo, K; Bourne, D [University of Oklahoma Health Sciences Center, Department of Pharmaceutical Sciences (United States); Grady, B [School of Chemical, Biological and Materials Engineering (United States); Awasthi, V [University of Oklahoma Health Sciences Center, Department of Pharmaceutical Sciences (United States)

    2011-06-15

    3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a 'drug-in-CD-in liposome' approach. An aqueous solution of EF24 and hydroxypropyl-{beta}-cyclodextrin (HP{beta}CD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze-thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HP{beta}CD mixture provided k{sub 1:1} value of 9.9 M{sup -1}. The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HP{beta}CD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 {+-} 2.6 nm) by dehydration-rehydration technique. With extrusion technique, the size of 177 {+-} 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 {mu}M dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an {alpha}-t{sub 1/2} of 21.4 min and {beta}-t{sub 1/2} of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using 'drug-in-CD-in liposome' approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution.

  18. Biodistribution and receptor imaging studies of insulin labelled with radioiodine in mice bearing H22 hepatocellular cacinoma

    International Nuclear Information System (INIS)

    Tang Gongshun; Kuang Anren; Liang Zenlu

    2004-01-01

    Objectives: It has been demonstrated that insulin receptor of hepatocellular carcinoma cells is overexpression. The biodistribution of 125I-insulin and receptor imaging studies of 131I-insulin in mice bearing solid liver tumor comprised of hepatic carcinoma H22 cells were performed to develop insulin as a carder of radioiodine. Methods: 1 )Insulin was radiolabeled with iodine-125 or iodine-131 using a Chloramines T method. Twenty mice bearing tumor were divided into 4 groups (n = 5 each) randomly. They were killed at 5, 15, 30, 60 min after 125I-insulin administered intravenously. The percentage of injected dose of 125I-insulin per gram of tissue(%ID/gdis) in mice bearing tumor were determined. 2) Another ten mice bearing tumor were selected to be as a inhibition group. They received cold insulin 2 mg intravenously 2 min ahead of administration of 125I-insulin and they were killed at 30 min (n=5) and 60 rain (n=5) randomly post 125I-insulin injection. The %ID/ginh and the inhibited rates[(%ID/gdis-%iD/ginh) %ID/gdis 100%] were obtained. 3) One tumor-mouse received 7.4 Mbq 13II-insulin intravenously, another received cold insulin 2 mg injection before 13II-insulin injection. Whole body images were carded out and the radioactivity ratios of tumor/normal were accounted at 60 min. Results: 1) The radiochemical purities of 125I-insulin and 13II-insulin were 96.7%-98.9%. The tumors uptake of the 125I-insulin increased gradually, its peak (%ID/gdis) was 3.44% 0.42% at 30 min, when the normal tissues uptake decreased sharply post-injection. The radioactivity ratio of the tumor/blood and tumor/muscle reached to 1.44 and 3.62 respectively at 60 min. 2)The tumor-inhibition rate was 32.07% at 30 min and 37.42% at 60 min. 3) A high radioactivity accumulation in tumor region could be seen in the mouse at 60 min post 131I-insulin injection. The radioactivity ratio of the tumor/normal tissue was 2.13 and it declined to 1.37 after received insulin 2 mg intervention. Conclusions

  19. Liposome-encapsulated EF24-HP{beta}CD inclusion complex: a preformulation study and biodistribution in a rat model

    Energy Technology Data Exchange (ETDEWEB)

    Agashe, H.; Lagisetty, P.; Sahoo, K.; Bourne, D. [University of Oklahoma Health Sciences Center, Department of Pharmaceutical Sciences (United States); Grady, B. [School of Chemical, Biological and Materials Engineering (United States); Awasthi, V., E-mail: vawasthi@ouhsc.edu [University of Oklahoma Health Sciences Center, Department of Pharmaceutical Sciences (United States)

    2011-06-15

    3,5-Bis(2-fluorobenzylidene)-4-piperidone (EF24) is an anti-proliferative diphenyldifluoroketone analog of curcumin with more potent activity. The authors describe a liposome preparation of EF24 using a 'drug-in-CD-in liposome' approach. An aqueous solution of EF24 and hydroxypropyl-{beta}-cyclodextrin (HP{beta}CD) inclusion complex (IC) was used to prepare EF24 liposomes. The liposome size was reduced by a combination of multiple freeze-thaw cycles. Co-encapsulation of glutathione inside the liposomes conferred them with the capability of labeling with imageable radionuclide Tc-99m. Phase solubility analysis of EF24-HP{beta}CD mixture provided k{sub 1:1} value of 9.9 M{sup -1}. The enhanced aqueous solubility of EF24 (from 1.64 to 13.8 mg/mL) due to the presence of HP{beta}CD helped in the liposome preparation. About 19% of the EF24 IC was encapsulated inside the liposomes (320.5 {+-} 2.6 nm) by dehydration-rehydration technique. With extrusion technique, the size of 177 {+-} 6.5 nm was obtained without any effect on encapsulation efficiency. The EF24-liposomes were evaluated for anti-proliferative activity in lung adenocarcinoma H441 and prostate cancer PC-3 cells. The EF24-liposomes demonstrated anti-proliferative activity superior to that of plain EF24 at 10 {mu}M dose. When injected in rats, the Tc-99m-labeled EF24-liposomes cleared from blood with an {alpha}-t{sub 1/2} of 21.4 min and {beta}-t{sub 1/2} of 397 min. Tissue radioactivity counting upon necropsy showed that the majority of clearance was due to the uptake in liver and spleen. The results suggest that using 'drug-in-CD-in liposome' approach is a feasible strategy to formulate an effective parenteral preparation of EF24. In vitro studies show that the liposomal EF24 remains anti-proliferative, while presenting an opportunity to image its biodistribution.

  20. Boron neutron capture therapy for clear cell sarcoma (CCS): biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models.

    Science.gov (United States)

    Andoh, T; Fujimoto, T; Sudo, T; Fujita, I; Imabori, M; Moritake, H; Sugimoto, T; Sakuma, Y; Takeuchi, T; Kawabata, S; Kirihata, M; Akisue, T; Yayama, K; Kurosaka, M; Miyatake, S; Fukumori, Y; Ichikawa, H

    2011-12-01

    Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake l-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of (10)B (45-74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg). Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Boron neutron capture therapy for clear cell sarcoma (CCS): Biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models

    Energy Technology Data Exchange (ETDEWEB)

    Andoh, T. [Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Fujimoto, T. [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Sudo, T. [Section of Translational Research, Hyogo Cancer Center, Akashi 673-0021 (Japan); Fujita, I.; Imabori, M. [Department of Orthopaedic Surgery, Hyogo Cancer Center, Akashi 673-0021 (Japan); Moritake, H. [Department of Pediatrics, Miyazaki University, Kiyotake 889-1692 (Japan); Sugimoto, T. [Department of Pediatrics, Saiseikai Shigaken Hospital, Ritto 520-3046 (Japan); Sakuma, Y. [Department of Pathology, Hyogo Cancer Center, Akashi 673-0021 (Japan); Takeuchi, T. [Department of Pathology, Kochi University, Nangoku 783-8505 (Japan); Kawabata, S. [Department of Neurosurgery, Osaka Medical College, Osaka 569-8686 (Japan); Kirihata, M. [Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Sakai 599-8531 (Japan); Akisue, T. [Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Yayama, K. [Laboratory of Cardiovascular Pharmacology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Kurosaka, M. [Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017 (Japan); Miyatake, S. [Department of Neurosurgery, Osaka Medical College, Osaka 569-8686 (Japan); Fukumori, Y. [Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan); Ichikawa, H., E-mail: ichikawa@pharm.kobegakuin.ac.jp [Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences and Cooperative Research Center of Life Sciences, Kobe Gakuin University, Kobe 650-8586 (Japan)

    2011-12-15

    Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake L-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of {sup 10}B (45-74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg).

  2. Boron neutron capture therapy for clear cell sarcoma (CCS): Biodistribution study of p-borono-L-phenylalanine in CCS-bearing animal models

    International Nuclear Information System (INIS)

    Andoh, T.; Fujimoto, T.; Sudo, T.; Fujita, I.; Imabori, M.; Moritake, H.; Sugimoto, T.; Sakuma, Y.; Takeuchi, T.; Kawabata, S.; Kirihata, M.; Akisue, T.; Yayama, K.; Kurosaka, M.; Miyatake, S.; Fukumori, Y.; Ichikawa, H.

    2011-01-01

    Clear cell sarcoma (CCS) is a rare melanocytic malignant tumor with a poor prognosis. Our previous study demonstrated that in vitro cultured CCS cells have the ability to highly uptake L-BPA and thus boron neutron capture therapy could be a new option for CCS treatment. This paper proved that a remarkably high accumulation of 10 B (45–74 ppm) in tumor was obtained even in a CCS-bearing animal with a well-controlled biodistribution followed by intravenous administration of L-BPA-fructose complex (500 mg BPA/kg).

  3. Biodistribution and toxicological study of PEGylated single-wall carbon nanotubes in the zebrafish (Danio rerio) nervous system

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Gisele E.B.; Dal Bosco, Lidiane [Laboratório de Neurociências, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande (FURG), Rio Grande, RS, 96210-900 (Brazil); Programa de Pós-graduação em Ciências Fisiológicas–Fisiologia Animal Comparada, FURG, Rio Grande, RS, 96210-900 (Brazil); Gonçalves, Carla O.F.; Santos, Adelina P. [Laboratório de Química de Nanoestruturas, Centro de Desenvolvimento da Tecnologia Nuclear, Belo Horizonte, MG, 31270-901 (Brazil); Fantini, Cristiano [Instituto de Ciências Exatas, Departamento de Física, Belo Horizonte, MG, 31270-901 (Brazil); Furtado, Clascídia A. [Laboratório de Química de Nanoestruturas, Centro de Desenvolvimento da Tecnologia Nuclear, Belo Horizonte, MG, 31270-901 (Brazil); Parfitt, Gustavo M.; Peixoto, Carolina [Laboratório de Neurociências, Instituto de Ciências Biológicas, Universidade Federal do Rio Grande (FURG), Rio Grande, RS, 96210-900 (Brazil); Programa de Pós-graduação em Ciências Fisiológicas–Fisiologia Animal Comparada, FURG, Rio Grande, RS, 96210-900 (Brazil); Romano, Luis Alberto [Instituto de Oceanografía, Universidade Federal do Rio Grande, Rio Grande, RS, 96210-030 (Brazil); and others

    2014-11-01

    Nanotechnology has been proven to be increasingly compatible with pharmacological and biomedical applications. Therefore, we evaluated the biological interactions of single-wall carbon nanotubes functionalized with polyethylene glycol (SWNT-PEG). For this purpose, we analyzed biochemical, histological, behavioral and biodistribution parameters to understand how this material behaves in vitro and in vivo using the fish Danio rerio (zebrafish) as a biological model. The in vitro results for fish brain homogenates indicated that SWNT-PEG had an effect on lipid peroxidation and GSH (reduced glutathione) content. However, after intraperitoneal exposure, SWNT-PEG proved to be less biocompatible and formed aggregates, suggesting that the PEG used for the nanoparticle functionalization was of an inappropriate size for maintaining product stability in a biological environment. This problem with functionalization may have contributed to the low or practically absent biodistribution of SWNT-PEG in zebrafish tissues, as verified by Raman spectroscopy. There was an accumulation of material in the abdominal cavity that led to inflammation and behavioral disturbances, as evaluated by a histological analysis and an open field test, respectively. These results provide evidence of a lack of biocompatibility of SWNTs modified with short chain PEGs, which leads to the accumulation of the material, tissue damage and behavioral alterations in the tested subjects. - Highlights: • In vitro brain exposure diminished lipid peroxidation. • In vitro brain exposure depletes the GSH content. • SWNT-PEG was not biocompatible and formed aggregates after the exposure. • Practically absent biodistribution of SWNT-PEG was observed by Raman spectroscopy. • SWNT-PEG exposure lead to tissue damage and inflammatory responses.

  4. Biodistribution and toxicological study of PEGylated single-wall carbon nanotubes in the zebrafish (Danio rerio) nervous system

    International Nuclear Information System (INIS)

    Weber, Gisele E.B.; Dal Bosco, Lidiane; Gonçalves, Carla O.F.; Santos, Adelina P.; Fantini, Cristiano; Furtado, Clascídia A.; Parfitt, Gustavo M.; Peixoto, Carolina; Romano, Luis Alberto

    2014-01-01

    Nanotechnology has been proven to be increasingly compatible with pharmacological and biomedical applications. Therefore, we evaluated the biological interactions of single-wall carbon nanotubes functionalized with polyethylene glycol (SWNT-PEG). For this purpose, we analyzed biochemical, histological, behavioral and biodistribution parameters to understand how this material behaves in vitro and in vivo using the fish Danio rerio (zebrafish) as a biological model. The in vitro results for fish brain homogenates indicated that SWNT-PEG had an effect on lipid peroxidation and GSH (reduced glutathione) content. However, after intraperitoneal exposure, SWNT-PEG proved to be less biocompatible and formed aggregates, suggesting that the PEG used for the nanoparticle functionalization was of an inappropriate size for maintaining product stability in a biological environment. This problem with functionalization may have contributed to the low or practically absent biodistribution of SWNT-PEG in zebrafish tissues, as verified by Raman spectroscopy. There was an accumulation of material in the abdominal cavity that led to inflammation and behavioral disturbances, as evaluated by a histological analysis and an open field test, respectively. These results provide evidence of a lack of biocompatibility of SWNTs modified with short chain PEGs, which leads to the accumulation of the material, tissue damage and behavioral alterations in the tested subjects. - Highlights: • In vitro brain exposure diminished lipid peroxidation. • In vitro brain exposure depletes the GSH content. • SWNT-PEG was not biocompatible and formed aggregates after the exposure. • Practically absent biodistribution of SWNT-PEG was observed by Raman spectroscopy. • SWNT-PEG exposure lead to tissue damage and inflammatory responses

  5. Boron nitride nanotubes radiolabeled with ⁹⁹mTc: preparation, physicochemical characterization, biodistribution study, and scintigraphic imaging in Swiss mice.

    Science.gov (United States)

    Soares, Daniel Crístian Ferreira; Ferreira, Tiago Hilário; Ferreira, Carolina de Aguiar; Cardoso, Valbert Nascimento; de Sousa, Edésia Martins Barros

    2012-02-28

    In the present study, boron nitride nanotubes (BNNTs) were synthesized from an innovative process and functionalized with a glycol chitosan polymer in CDTN (Centro de Desenvolvimento da Tecnologia Nuclear) laboratories. As a means of studying their in vivo biodistribution behavior, these nanotubes were radiolabeled with (99m)Tc and injected in mice. Their size, distribution, and homogeneity were determined by photon correlation spectroscopy (PCS), while their zeta potential was determined by laser Doppler anemometry. The morphology and structural organization were evaluated by scanning electron microscopy (SEM). The functionalization in the nanotubes was evaluated by thermogravimetry analysis (TGA) and Fourier transformer infrared spectroscopy. The results showed that BNNTs were obtained and functionalized successfully, reaching a mean size and dispersity deemed adequate for in vivo studies. The BNNTs were also evaluated by ex vivo biodistribution studies and scintigraphic imaging in healthy mice. The results showed that nanostructures, after 24h, having accumulated in the liver, spleen and gut, and eliminated via renal excretion. The findings from this study reveal a potential application of functionalized BNNTs as new potential drugs or radioisotope nanocarriers to be applied in therapeutic procedures. Copyright © 2011 Elsevier B.V. All rights reserved.

  6. Synthesis and study of bio-distribution of a piperidine derivative marked by the technetium 99m

    International Nuclear Information System (INIS)

    Guizani, Sihem

    2008-01-01

    With the increase in life expectancy and ageing, the cerebral diseases, became among the first causes of mortality of the population. However, the prevention and the treatment of these diseases depend on the diagnosis and an early and reliable assessment. The radio pharmaceutics used are very few. The object of our work concerns the development of a new radiotracer labelled with the Tc 99m, it's a piperidine derivative (the 1 piperidine-1-yl ferrocene-1-one), then to follow the kinetics and its biodistribution in rats to detect its targets. The follow-up of kinetics and the biodistribution of the lately synthesized molecule after their injection, revealed a cerebral activity of 0.82 pour cent. This value represents a sufficient quantity to be detected by an external device of acquisition of radioactivity like gamma camera without health threatens of the patient. The method of labelling developed opens a new way of synthesis of characterized by radiochemical stability and a very promising biochemical behavior for the cerebral radiodiagnosis. (Author)

  7. Use of magnetic resonance to study biodistribution of dextran-coated magnetic fluid intravenously administered in mice

    International Nuclear Information System (INIS)

    Lacava, L.M.; Lacava, Z.G.M.; Azevedo, R.B.; Chaves, S.B.; Garcia, V.A.P.; Silva, O.; Pelegrini, F.; Buske, N.; Gansau, C.; Da Silva, M.F.; Morais, P.C.

    2002-01-01

    Magnetic resonance was used to investigate the kinetic disposition and the subsequent biodistribution of dextran-coated magnetite nanoparticles (9.4 nm core diameter) after intravenous injection of a bolus dose in female Swiss mice. The X-band spectra show a broad single-line at g∼2, typical of nanomagnetic particles suspended in a non-magnetic matrix. In the first 90 min the time-decay of the nanoparticle concentration in the bloodstream follows the one-exponential (one-compartment) model with a half-life of 6.9 min. With respect to blood the clearance (90 μl/min) and the volume of distribution (900 μl) were obtained from the magnetic resonance data. Magnetite nanoparticles were found 90 min after administration in liver and spleen with a typical absorption half-life of 14 min

  8. Biodistribution of radiolabeled lymphocytes

    International Nuclear Information System (INIS)

    Fawwaz, R.A.; Oluwole, S.; Wang, T.S.; Kuromoto, N.; Iga, C.; Hardy, M.A.; Alderson, P.O.

    1985-01-01

    Factors that might affect the biodistribution and clinical utility of radiolabeled lymphocytes were evaluated in experimental animals. Indium-111 (In-111) labeled lymphocytes obtained from peripheral blood, lymph node, or spleen were found in significant amounts in the lymphoid tissues of Lewis rats as early as 3 hours after infusion. A progressive increase in nodal activity with concomitant fall of activity in other organs followed, indicating active recirculation of the lymphocytes. In vitro irradiation of the In-111 labeled lymphocytes resulted in no detectable lymphocyte recirculation and/or reduced localization in lymphoid tissue. Splenectomized animals and those sensitized to an organ allograft before cell infusion showed increased activity in their bone marrow. These results suggest that the source of the injected cells, cell irradiation dose level and host sensitization should be considered when radiolabeled lymphocytes are being prepared for use in clinical diagnosis and therapy

  9. Biodistribution dosimetric study of radiopharmaceutical 99mTc Ixolaris in mice for melanoma diagnosis by molecular image and translational model for human beings

    International Nuclear Information System (INIS)

    Soriano, Sarah Canuto Silva

    2015-01-01

    The labeling of Ixolaris with 99m Tc was developed by Barboza et.al. (2013) aiming its use primarily in glioblastoma and after in melanoma diagnosis, a less common but very aggressive cancer and with high mortality rate. Preliminary tests on animals have proven its effectiveness of labeling but a dosimetric study to human clinical trials should be performed. This study aimed to: (1) determine the biokinetic model for the radiotracer 99m Tc-Ixolaris in mice by imaging dosimetry method; and (2) estimate the absorbed and effective dose resulting from the use of a new radiopharmaceutical for melanoma and metastases diagnosis in human beings, since a dosimetric study of new radiopharmaceuticals in animals is necessary to test them subsequently in humans and apply for registration in ANVISA. According to SPECT images, was found a latency period of 15 to 21 days for the development of lung metastasis in mice. Three C57BL6 mice, one control animal, and two animals with induced cell line B16-F10 murine melanoma were tested. The 99m Tc-Ixolaris radiopharmaceutical was administered intravenously in a caudal vein, and SPECT images were acquired 0.5 h, 1.5 h, 2.5 h, 3.5 h and 24 h post-administration for analysis and biodistribution quantification. The biokinetic model was determined and thus, obtained cumulative activity in order to estimate the absorbed dose in each organ. The mass and metabolic differences between mice and humans were considered and used to extrapolate the data acquired at different scales. Based on dose factors provided by the software MIRDOSE and Olinda (S factor), absorbed doses in irradiated target organs were calculated for the source organs, and finally the effective dose was estimated. The results indicate that for diagnostic exams conducted in human melanoma patients by administering approximately 25.7 MBq the estimated effective dose was 4.3 mSv. Comparing with effective doses obtained in other diagnostic techniques with 99m Tc, a range of effective

  10. Preclinical acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of ["1"8F]fluorocholine in mice

    International Nuclear Information System (INIS)

    Silveira, Marina B.; Ferreira, Soraya M.Z.M.D.; Nascimento, Leonardo T.C.; Costa, Flávia M.; Mendes, Bruno M.; Ferreira, Andrea V.; Malamut, Carlos; Silva, Juliana B.; Mamede, Marcelo

    2016-01-01

    ["1"8F]Fluorocholine (["1"8F]FCH) has been proven to be effective in prostate cancer. Since ["1"8F]FCH is classified as a new radiopharmaceutical in Brazil, preclinical safety and efficacy data are required to support clinical trials and to obtain its approval. The aim of this work was to perform acute toxicity, biodistribution, pharmacokinetics, radiation dosimetry and microPET imaging studies of ["1"8F]FCH. The results could support its use in nuclear medicine as an important piece of work for regulatory in Brazil. - Highlights: • Data demonstrated the high quality, safety and effectiveness of ["1"8F]FCH. • ["1"8F]FCH preclinical profile is in accordance with previously published. • Toxicity, distribution, kinetics and radiation dosimetry were well characterized. • The results are important for regulatory issues in Brazil and other countries.

  11. Technetium-99m radiolabeling of a recombinant dermonecrotic protein (recLiD1) from the Loxosceles venom for biodistribution study

    International Nuclear Information System (INIS)

    Valadares, D.; Felicori, L.; Olortegui, C.C.; Simal, C.; Gouvea dos Santos, R.

    2007-01-01

    In the present study the recombinant form (recLiD1) of a dermonecrotic protein present in the Brazilian brown spider Loxosceles intermedia venom was labeled with technetium-99m using stannous chloride and sodium borohydride as reducing agents. 99mTc-recLiD 1 kept its biological activity evoking dermonecrotic activity in rabbits. In vivo biodistribution in mice with the radiolabeled recLiD 1 showed high kidney uptake followed by stomach and liver uptakes. Also, we can see that 20% of toxin remaining in the skin after 120 min and once absorbed, 99mTc-recLiD 1 is rapidly cleared from the blood with long-lasting. We also observed one displacement of 99mTc-recLiD 1 by one monoclonal antibody raised against L. intermedia venom that indicates specific interaction with kidney tissue. (author)

  12. Lyophilization and rehydration of polymer-coated lipid vesicles containing a lipophilic chelator in the presence of sucrose: Labeling with99m Tc and biodistribution studies

    International Nuclear Information System (INIS)

    Szucs, Margaret; Tilcock, Colin

    1995-01-01

    In this paper we describe studies of the effect of lyophilization and rehydration of polymer-coated lipid vesicles bearing a lipophilic surface chelator upon subsequent labeling with technetium-99m and in vivo biodistribution behavior. Unilamellar vesicles of average diameter 100 nm were prepared containing 2 mol% of the lipophilic chelator phosphatidylethanolamine-diethylenetriaminetetraacetic acid (PE-DTTA) and either 0 or 3 mol% of the lipid-polymer conjugate, dipalmitoyl-phosphatidylethanolamine-monomethoxy polyethylene glycol 5000 (PE-MPEG) in 0.9% sodium chloride to which was added varying amounts of sucrose to a final concentration of 100-500 mM. The size of the vesicles in sucrose was determined before lyophilization and after rehydration and the effect of sucrose on the ability to label the vesicles with pertechnetate in the presence of stannous chloride was determined. Biodistribution studies were done in rabbits with vesicles before lyophilization and after rehydration in order to determine whether the rate of clearance from the blood pool was affected by the lyophilization/rehydration procedure. Results demonstrate that vesicles containing PE-DTTA and without PE-MPEG can be lyophilized and rehydrated with no change in average size or size distribution so long as the external sucrose concentration is greater than approx. 250 mM. When PE-MPEG is also present in the membrane the average vesicle size increases from approx. 140 to 200 nm, consistent with vesicle fusion. However, this small change in vesicle size makes no difference to the resulting circulation half-life. In no case does the presence of sucrose on the exterior of the vesicle interfere with technetium labeling of the vesicle surface

  13. Radiosynthesis of N-¹¹C-Methyl-Taurine-Conjugated Bile Acids and Biodistribution Studies in Pigs by PET/CT.

    Science.gov (United States)

    Schacht, Anna Christina; Sørensen, Michael; Munk, Ole Lajord; Frisch, Kim

    2016-04-01

    During cholestasis, accumulation of conjugated bile acids may occur in the liver and lead to hepatocellular damage. Inspired by our recent development of N-(11)C-methyl-glycocholic acid-that is, (11)C-cholylsarcosine-a tracer for PET of the endogenous glycine conjugate of cholic acid, we report here a radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids and biodistribution studies in pigs by PET/CT. A radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids was developed and used to prepare N-(11)C-methyl-taurine conjugates derived from cholic, chenodeoxycholic, deoxycholic, ursodeoxycholic, and lithocholic acid. The lipophilicity of these new tracers was determined by reversed-phase thin-layer chromatography. The effect of lipophilicity and structure on the biodistribution was investigated in pigs by PET/CT using the tracers derived from cholic acid (3α-OH, 7α-OH, 12α-OH), ursodeoxycholic acid (3α-OH, 7β-OH), and lithocholic acid (3α-OH). The radiosyntheses of the N-(11)C-methyl-taurine-conjugated bile acids proceeded with radiochemical yields of 61% (decay-corrected) or greater and radiochemical purities greater than 99%. PET/CT in pigs revealed that the tracers were rapidly taken up by the liver and secreted into bile. There was no detectable radioactivity in urine. Significant reflux of N-(11)C-methyl-taurolithocholic acid into the stomach was observed. We have successfully developed a radiosynthesis of N-(11)C-methyl-taurine-conjugated bile acids. These tracers behave in a manner similar to endogenous taurine-conjugated bile acids in vivo and are thus promising for functional PET of patients with cholestatic diseases. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  14. Biodistribution and PET imaging of [18F]-fluoroadenosine derivatives

    International Nuclear Information System (INIS)

    Alauddin, Mian M.; Shahinian, Antranik; Park, Ryan; Tohme, Michael; Fissekis, John D.; Conti, Peter S.

    2007-01-01

    Introduction: Many fluorinated analogues of adenosine nucleoside have been synthesized and studied as potential antitumor and antiviral agents. Earlier, we reported radiosynthesis of 2'-deoxy-2'-[ 18 F]fluoro-1-β-D-arabinofuranosyl-adenine ([ 18 F]-FAA) and 3'-deoxy-3'-[ 18 F]fluoro-1-β-D-xylofuranosyl-adenine ([ 18 F]FXA). Now, we report their in vivo studies including blood clearance, biodistribution and micro-PET imaging in tumor-bearing nude mice. Methods: Tumors were grown in 6-week-old athymic nude mice (Harlan, Indianapolis, IN, USA) by inoculation of HT-29 cells, wild-type cells in the left flank and transduced cells with HSV-tk on the right flank. When the tumor was about 1 cm in size, animals were injected with these radiotracers for in vivo studies, including blood clearance, micro-PET imaging and biodistribution. Results: Uptake of [ 18 F]FAA in tumor was 3.3-fold higher than blood, with highest uptake in the spleen. Maximum uptake of [ 18 F]FXA was observed in the heart compared to other organs. There was no tumor uptake of [ 18 F]FXA. Biodistribution results were supported by micro-PET images, which also showed very high uptake of [ 18 F]FAA in spleen and visualization of tumors, and high uptake of [ 18 F]FXA in the heart. Conclusion: These results suggest that [ 18 F]FAA may be useful for tumor imaging, while [ 18 F]FXA may have potential as a heart imaging agent with PET

  15. Radiolabeling, biodistribution and tumor imaging of stealth liposomes containing methotrexate

    International Nuclear Information System (INIS)

    Subramanian, N; Arulsudar, N; Chuttani, K; Mishra, P; Sharma, R.K; Murthy, R.S.R

    2003-01-01

    To study the utility of sterically stabilized liposomes (stealth liposomes) in tumor scintigraphy by studying its biodistribution and accumulation in target tissue after radiolabeling with Technetium-99m (99mTC). Conventional and Stealth liposomes were prepared by lipid film hydration method using methotrexate as model anticancer drug. Radiolabeling of the liposomes was carried out by direct labeling using reduced 99mTc. Experimental conditions for maximum labeling yield were optimized. The stability studies were carried out to check binding strength of the radiolabeled complexes. The blood kinetic study was carried out in rabbits after giving the labeled complex by intravenous administration through ear vein. The biodistribution studies were carried out in the Ehrlich ascites tumor (EAT) bearing mice after intravenous administration through tail vein, showed prolonged circulation in blood and significant increase in the accumulation in tumor for the sterically stabilized liposomes compared to the conventional liposomes. The gamma scintigraphic image shows the distribution of the stealth liposomes in liver, spleen, kidney and tumor. The study gives precise idea about the use of stealth liposomes in tumor scintigraphy and organ distribution studies (Au)

  16. Labelling, biodistribution and compartmental analysis of N-acetylcysteine labelled with Tc-99m. Comparative investigation with with 99m Tc-MIBI in an in vivo tumoral model

    International Nuclear Information System (INIS)

    Faintuch, Bluma Linkowski

    1997-01-01

    Labelling and biodistribution studies were done with two different ligands, respectively Methoxy isobutyl isonitrile (MIBI) and N-acetylcysteine (NAC), employing Tc-99m as a tracer. The main objective was to assess the pharmacokinetic properties of the second substance, aiming at its possible application in cancer diagnosis. To this purpose an in vivo investigation was done using healthy and tumor-bearing rats with experimental cancer. Images of tumor-bearing rats registered in a scintillation camera indicated that with 99m Tc-MIBI none of the two selected times was adequate for visualization of the cancer mass. In contrast, 99m Tc-NAC permitted clear identification of the humor, four hours after injection. The results have demonstrated that 99m Tc-NAC is a radiopharmaceutical with affinity for cancer tissue and promising for further investigation concerning imaging diagnosis of tumors. (author)

  17. Experimental Studies of Boronophenylalanine ({sup 10}BPA) Biodistribution for the Individual Application of Boron Neutron Capture Therapy (BNCT) for Malignant Melanoma Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Carpano, Marina; Perona, Marina; Rodriguez, Carla [Department of Radiobiology, National Atomic Energy Commission, San Martín (Argentina); Nievas, Susana; Olivera, Maria; Santa Cruz, Gustavo A. [Department of Boron Neutron Capture Therapy, National Atomic Energy Commission, San Martín (Argentina); Brandizzi, Daniel; Cabrini, Romulo [Department of Radiobiology, National Atomic Energy Commission, San Martín (Argentina); School of Dentistry, University of Buenos Aires, Buenos Aires (Argentina); Pisarev, Mario [Department of Radiobiology, National Atomic Energy Commission, San Martín (Argentina); National Research Council of Argentina, Buenos Aires (Argentina); Department of Human Biochemistry, School of Medicine, University of Buenos Aires, Buenos Aires (Argentina); Juvenal, Guillermo Juan [Department of Radiobiology, National Atomic Energy Commission, San Martín (Argentina); National Research Council of Argentina, Buenos Aires (Argentina); Dagrosa, Maria Alejandra, E-mail: dagrosa@cnea.gov.ar [Department of Radiobiology, National Atomic Energy Commission, San Martín (Argentina); National Research Council of Argentina, Buenos Aires (Argentina)

    2015-10-01

    Purpose: Patients with the same histopathologic diagnosis of cutaneous melanoma treated with identical protocols of boron neutron capture therapy (BNCT) have shown different clinical outcomes. The objective of the present studies was to evaluate the biodistribution of boronophenilalanina ({sup 10}BPA) for the potential application of BNCT for the treatment of melanoma on an individual basis. Methods and Materials: The boronophenilalanine (BPA) uptake was evaluated in 3 human melanoma cell lines: MEL-J, A375, and M8. NIH nude mice were implanted with 4 10{sup 6} MEL-J cells, and biodistribution studies of BPA (350 mg/kg intraperitoneally) were performed. Static infrared imaging using a specially modified infrared camera adapted to measure the body infrared radiance of small animals was used. Proliferation marker, Ki-67, and endothelial marker, CD31, were analyzed in tumor samples. Results: The in vitro studies demonstrated different patterns of BPA uptake for each analyzed cell line (P<.001 for MEL-J and A375 vs M8 cells). The in vivo studies showed a maximum average boron concentration of 25.9 ± 2.6 μg/g in tumor, with individual values ranging between 11.7 and 52.0 μg/g of {sup 10}B 2 hours after the injection of BPA. Tumor temperature always decreased as the tumors increased in size, with values ranging between 37°C and 23°C. A significant correlation between tumor temperature and tumor-to-blood boron concentration ratio was found (R{sup 2} = 0.7, rational function fit). The immunohistochemical studies revealed, in tumors with extensive areas of viability, a high number of positive cells for Ki-67, blood vessels of large diameter evidenced by the marker CD31, and a direct logistic correlation between proliferative status and boron concentration difference between tumor and blood (R{sup 2} = 0.81, logistic function fit). Conclusion: We propose that these methods could be suitable for designing new screening protocols applied before melanoma BNCT

  18. Whole-body biodistribution and brain PET imaging with [{sup 18}F]AV-45, a novel amyloid imaging agent - a pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Lin, K.-J. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taiwan (China); Hsu, W.-C. [Department of Neurology, Chang Gung Memorial Hospital, Taiwan (China); Hsiao, I.-T.; Wey, S.-P. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taiwan (China); Jin, L.-W. [M.I.N.D. Institute and Department of Pathology, University of California, Davis, CA (United States); Skovronsky, Daniel [Avid Radiopharmaceuticals, Inc., Philadelphia, PA (United States); Wai, Y.-Y. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Department of Radiology, Chang Gung Memorial Hospital, Taiwan (China); Chang, H.-P.; Lo, C.-W.; Yao, C.H.; Yen, T.-C. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Kung, M.-P. [Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taiwan (China); Department of Radiology, University of Pennsylvania, Philadelphia, PA (United States)

    2010-05-15

    Purpose: The compound (E)-4-(2-(6-(2-(2-(2-{sup 18}F-fluoroethoxy)ethoxy)ethoxy) pyridin-3-yl)vinyl)-N-methylbenzenamine ([{sup 18}F]AV-45) is a novel radiopharmaceutical capable of selectively binding to {beta}-amyloid (A{beta}) plaques. This pilot study reports the safety, biodistribution, and radiation dosimetry of [{sup 18}F]AV-45 in human subjects. Methods: In vitro autoradiography and fluorescent staining of postmortem brain tissue from patients with Alzheimer's disease (AD) and cognitively healthy subjects were performed to assess the specificity of the tracer. Biodistribution was assessed in three healthy elderly subjects (mean age: 60.0{+-}5.2 years) who underwent 3-h whole-body positron emission tomography (PET)/computed tomographic (CT) scans after a bolus injection of 381.9{+-}13.9 MBq of [{sup 18}F]AV-45. Another six subjects (three AD patients and three healthy controls, mean age: 67.7{+-}13.6 years) underwent brain PET studies. Source organs were delineated on PET/CT. All subjects underwent magnetic resonance imaging (MRI) for obtaining structural information. Results: In vitro autoradiography revealed exquisitely high specific binding of [{sup 18}F]AV-45 to postmortem AD brain sections, but not to the control sections. There were no serious adverse events throughout the study period. The peak uptake of the tracer in the brain was 5.12{+-}0.41% of the injected dose. The highest absorbed organ dose was to the gallbladder wall (184.7{+-}78.6 {mu}Gy/MBq, 4.8 h voiding interval). The effective dose equivalent and effective dose values for [{sup 18}F]AV-45 were 33.8{+-}3.4 {mu}Sv/MBq and 19.3{+-}1.3 {mu}Sv/MBq, respectively. Conclusion: [{sup 18}F]AV-45 binds specifically to A{beta} in vitro, and is a safe PET tracer for studying A{beta} distribution in human brain. The dosimetry is suitable for clinical and research application.

  19. Biodistribution of Different Sized Nanodiamonds in Mice.

    Science.gov (United States)

    Purtov, Konstantin; Petunin, Alexey; Inzhevatkin, Evgeny; Burov, Andrey; Ronzhin, Nikita; Puzyr, Alexey; Bondar, Vladimir

    2015-02-01

    The particle size is one of critical parameters influencing the biodistribution of detonation nanodiamonds (DND) after their administration into the body. As DNDs are prone to aggregation, the difference between their sizes in aqueous and physiological solutions has to be taken into account. Radioactive I125-BSA molecules were covalently immobilized on DNDs divided in three fractions of different average size. The DND-BSAI125 conjugates were intravenously administrated into adult mice and the particle allocation in the animal's organs and blood was evaluated based on the radioactivity distribution. We conclude that most of the conjugates were taken from the bloodstream and trapped in the liver and spleen. The short-term distribution pattern for all DNDs was similar regardless of size and practically unchanged with time. No significant clearance of the particles was observed for 4 h, but the presence of DNDs was detected in the blood. It was found that the largest particles tend to accumulate more into the liver as compared to the smaller ones. However, the size effect was not well pronounced for the studied size range.

  20. Biodistribution of the radiopharmaceutical sodium pertechnetate after biliopancreatic bypass with a duodenal switch

    International Nuclear Information System (INIS)

    Araujo-Filho, Irami; Rego, Amalia Cinthia Meneses; Brandao-Neto, Jose; Villarim-Neto, Arthur; Egito, Eryvaldo Socrates Tabosa; Azevedo, Italo Medeiros; Medeiros, Aldo Cunha

    2007-01-01

    Study with the purpose to examine the effects of duodenal switch (DS), regularly performed in morbidly obese patients, on biodistribution of sodium pertechnetate in several organs of rats. There was no early or late mortality in either rats groups. The values of percent radioactivity per gram of tissue (%ATI/g), showed no significant difference in liver, stomach, small bowel, duodenum, kidney, heart, bladder, bone and brain, when compared the DS rats with sham and controls rats. A postoperative significant increase (p<0.05) in mean %ATI/g levels was observed in spleen, pancreas and muscle in group DS rats, as compared to group S and C rats. In the lung there was an increase and in thyroid a decrease in mean %ATI/g of DS rats, when compared to sham rats (p<0.05). In conclusion, the biliopancreatic diversion with duodenal switch in rats modified the biodistribution of sodium pertechnetate in thyroid, lung, pancreas, spleen and muscle. (author)

  1. Biodistribution of the radiopharmaceutical sodium pertechnetate after biliopancreatic bypass with a duodenal switch

    Energy Technology Data Exchange (ETDEWEB)

    Araujo-Filho, Irami; Rego, Amalia Cinthia Meneses; Brandao-Neto, Jose; Villarim-Neto, Arthur; Egito, Eryvaldo Socrates Tabosa; Azevedo, Italo Medeiros; Medeiros, Aldo Cunha [Universidade Federal do Rio Grande do Norte, Natal, RN (Brazil). Programa de Pos-graduacao em Ciencias da Saude]. E-mail: aldo@ufrnet.br

    2007-09-15

    Study with the purpose to examine the effects of duodenal switch (DS), regularly performed in morbidly obese patients, on biodistribution of sodium pertechnetate in several organs of rats. There was no early or late mortality in either rats groups. The values of percent radioactivity per gram of tissue (%ATI/g), showed no significant difference in liver, stomach, small bowel, duodenum, kidney, heart, bladder, bone and brain, when compared the DS rats with sham and controls rats. A postoperative significant increase (p<0.05) in mean %ATI/g levels was observed in spleen, pancreas and muscle in group DS rats, as compared to group S and C rats. In the lung there was an increase and in thyroid a decrease in mean %ATI/g of DS rats, when compared to sham rats (p<0.05). In conclusion, the biliopancreatic diversion with duodenal switch in rats modified the biodistribution of sodium pertechnetate in thyroid, lung, pancreas, spleen and muscle. (author)

  2. The experimental study on biodistribution and radioimmunoimaging of 131I labeled anti-lymphoma Fab antibody in nude mice bearing human B cell lymphoma

    International Nuclear Information System (INIS)

    Yang Xiaochun; Zhang Meihua; Shen Junkang; Shen Yongmei; Shi Yizhen; Liu Zengli

    2008-01-01

    Objective: Radioimmunoimaging is still an interesting study in the domain of nuclear medicine. The aim of this study was to evaluate the biodistribution and radioimmunoimaging of 131 I-Fab anti- body in nude mice beating human B cell lymphoma. Methods: The immunoreactivity of Fab antibody to Raji cells was analyzed by immunohistochemistry and flow cytometry. Fab antibody and CD20 monoclonal antibody (as control) were labeled with 131 I using Iodogen method. 131 I-Fab antibody or 131 I-CD20 was injected into nude mice bearing B cell lymphoma via tail veins. The biodistribution and radioimmunoimaging results were obtained at 2, 4, 8 and 24 h postinjection, respectively. Results: The results of immunohistochemistry and flow cytometry indicated that both Fab antibody and 131 I-Fab antibody could bind strongly with membrane antigens on Raji cells, and the binding rate reached above 87%. Clear tumor image was obtained at 8 h after injection with 131 I-Fab and elimination was observed at 24 h postinjection. The clear tumor image for 131 I-CD20 antibody was obtained at 24 h post injection. The biodistribution in vivo showed that the percentage activities of injection dose per gram of tumor (% ID/g) of 131 I-Fab group at 2, 4, 8 h postinjection were higher than that of 131 I-CD20 antibody [(1.37±0.28), (1.84±0.13), (2.21±0.15)% ID/g vs (0.33±0.06), (0.62±0.08), (1.46±0.24)% ID/g, respectively; F=52.22, 278.42 and 29.00, all P 131 I-Fad and 131 I-CD20 groups at 2, 4, 8 and 24 h were [(0.22±0.03)-(5.44± 0.31)] vs[(0.04±0.01)-(3.10±0.29)], [(0.43±0.11) - (21.01±3.97)] vs [(0.11±0.05) - (7.99±1.81)], [(1.09±0.07) -(20.28±2.77)] vs [(0.48±0.06) - (23.55±1.69)], [(1.12± 0.02) - (10.29±1.78)] vs [(2.32 ± 0.34) - (33.23±6.83)], respectively. Conclusion: 131 I-Fab anti- body has advantages of small molecular weight, excellent targeting characteristics, early imaging and fast elimination, which indicates the potential application value in diagnosing B cell

  3. Preparation and standardization of an 'in vitro' labeling methodology and study of [99mTc]-EDDA/tricine/HYNIC-[Tyr3]-octreotide biodistribution

    International Nuclear Information System (INIS)

    Hernandes Melero, Laura Terumi Ueda

    2008-01-01

    -HYNIC, 10 mg of EDDA, 20 mg of tricine, 150 g of Sn C 12 .2H 2 O in a final pH 8.0, and activity up to 3700 MBq (100 mCi). This formulation can be an alternative for the administration of more than one patient per labeling procedure, using a lyophilized reagent. The biodistribution performed by invasive method in the intervals of 1.5 and 4 hours after intravenous administration of the radiopharmaceutical in Swiss mice determined the percentage of the activity administered in the blood and the various organs. The biodistribution data in Swiss and Nude mice bearing AR42J tumor (rat pancreatic adenocarcinoma) were compatible with the distribution of the labeled peptide: fast blood clearance, high uptake in the kidneys due to the elimination by the urinary tract, and high uptake in organs with high density of somatostatin receptors like lung, stomach, pancreas and tumor in the case of Nude mice. The uptake of the radiolabeled peptide in the abdominal region was not significant and represents an advantage related to the diagnosis of neuroendocrine tumors, frequently found in this region. The labeling and biodistribution results described in this study showed the potential of the 99m Tc-labeled peptide to be applied in diagnostic procedures in nuclear medicine. (author)

  4. Preparation and standardization of an 'in vitro' labelling methodology and study of [99m Tc]-EDDA/Tricine/Hynic-[Tyr3]-octreotide biodistribution

    International Nuclear Information System (INIS)

    Hernandes Melero, Laura Terumi Ueda

    2008-01-01

    g octreotide-HYNIC, 10 mg of EDDA, 20 mg of tricine, 150 μg of SnCI 2 .2H 2 0 in a final pH 8.0, and activity up to 3700 MBq (100 mCi). This formulation can be an alternative for the administration of more than one patient per labeling procedure, using a lyophilized reagent. The biodistribution performed by invasive method in the intervals of 1.5 and 4 hours after intravenous administration of the radiopharmaceutical in Swiss mice determined the percentage of the activity administered in the blood and the various organs. The biodistribution data in Swiss and Nude mice bearing AR42J tumor (rat pancreatic adenocarcinoma) were compatible with the distribution of the labeled peptide: fast blood clearance, high uptake in the kidneys due to the elimination by the urinary tract, and high uptake in organs with high density of somatostatin receptors like lung, stomach, pancreas and tumor in the case of Nude mice. The uptake of the radiolabeled peptide in the abdominal region was not significant and represents an advantage related to the diagnosis of neuroendocrine tumors, frequently found in this region. The labeling and biodistribution results described in this study showed the potential of the 99m Tc-labeled peptide to be applied in diagnostic procedures in nuclear medicine. (author)

  5. A study of the uptake and biodistribution of nano-titanium dioxide using in vitro and in vivo models of oral intake

    Energy Technology Data Exchange (ETDEWEB)

    MacNicoll, Alan; Kelly, Mick [The Food and Environment Research Agency (United Kingdom); Aksoy, Hatice [TÜBİTAK Marmara Research Center, Food Institute (Turkey); Kramer, Evelien; Bouwmeester, Hans [RIKILT - Institute of Food Safety (Netherlands); Chaudhry, Qasim, E-mail: qasim.chaudhry@fera.gsi.gov.uk [The Food and Environment Research Agency (United Kingdom)

    2015-02-15

    Certain food additives may contain a sizeable fraction of particles in the nanoscale. However, little is known about the fate, behaviour and toxicological effects of orally-ingested nanoparticles. This study investigated the uptake and biodistribution of nano- and larger-sized titanium dioxide (TiO{sub 2}) using an in vitro model of gut epithelium and in vivo in rat. The results of the in vivo study showed that oral administration of 5 mg/kg body weight of TiO{sub 2} nano- or larger particles did not lead to any significant translocation of TiO{sub 2} (measured as titanium) either to blood, urine or to various organs in rat at any of the time intervals studied over a 96 h post-administration period. Different methods used for dispersing particles did not affect the uptake, and orally administered TiO{sub 2} was found excreted in the faeces over a period of time. The in vitro study provided further evidence for the lack of translocation of TiO{sub 2} across the gut epithelium model. The overall evidence from both in vivo and in vitro studies did not support that oral ingestion of nano- or larger particles of TiO{sub 2} via food would result in any significant internal exposure of the consumer to the nanoparticles. The dietary TiO{sub 2} nanoparticles are likely to be excreted in the faeces.

  6. A study of the uptake and biodistribution of nano-titanium dioxide using in vitro and in vivo models of oral intake

    Science.gov (United States)

    MacNicoll, Alan; Kelly, Mick; Aksoy, Hatice; Kramer, Evelien; Bouwmeester, Hans; Chaudhry, Qasim

    2015-02-01

    Certain food additives may contain a sizeable fraction of particles in the nanoscale. However, little is known about the fate, behaviour and toxicological effects of orally-ingested nanoparticles. This study investigated the uptake and biodistribution of nano- and larger-sized titanium dioxide (TiO2) using an in vitro model of gut epithelium and in vivo in rat. The results of the in vivo study showed that oral administration of 5 mg/kg body weight of TiO2 nano- or larger particles did not lead to any significant translocation of TiO2 (measured as titanium) either to blood, urine or to various organs in rat at any of the time intervals studied over a 96 h post-administration period. Different methods used for dispersing particles did not affect the uptake, and orally administered TiO2 was found excreted in the faeces over a period of time. The in vitro study provided further evidence for the lack of translocation of TiO2 across the gut epithelium model. The overall evidence from both in vivo and in vitro studies did not support that oral ingestion of nano- or larger particles of TiO2 via food would result in any significant internal exposure of the consumer to the nanoparticles. The dietary TiO2 nanoparticles are likely to be excreted in the faeces.

  7. A study of the uptake and biodistribution of nano-titanium dioxide using in vitro and in vivo models of oral intake

    International Nuclear Information System (INIS)

    MacNicoll, Alan; Kelly, Mick; Aksoy, Hatice; Kramer, Evelien; Bouwmeester, Hans; Chaudhry, Qasim

    2015-01-01

    Certain food additives may contain a sizeable fraction of particles in the nanoscale. However, little is known about the fate, behaviour and toxicological effects of orally-ingested nanoparticles. This study investigated the uptake and biodistribution of nano- and larger-sized titanium dioxide (TiO 2 ) using an in vitro model of gut epithelium and in vivo in rat. The results of the in vivo study showed that oral administration of 5 mg/kg body weight of TiO 2 nano- or larger particles did not lead to any significant translocation of TiO 2 (measured as titanium) either to blood, urine or to various organs in rat at any of the time intervals studied over a 96 h post-administration period. Different methods used for dispersing particles did not affect the uptake, and orally administered TiO 2 was found excreted in the faeces over a period of time. The in vitro study provided further evidence for the lack of translocation of TiO 2 across the gut epithelium model. The overall evidence from both in vivo and in vitro studies did not support that oral ingestion of nano- or larger particles of TiO 2 via food would result in any significant internal exposure of the consumer to the nanoparticles. The dietary TiO 2 nanoparticles are likely to be excreted in the faeces

  8. Preclinical safety, toxicology, and biodistribution study of adenoviral gene therapy with sVEGFR-2 and sVEGFR-3 combined with chemotherapy for ovarian cancer.

    Science.gov (United States)

    Tuppurainen, Laura; Sallinen, Hanna; Kokki, Emmi; Koponen, Jonna; Anttila, Maarit; Pulkkinen, Kati; Heikura, Tommi; Toivanen, Pyry; Hämäläinen, Kirsi; Kosma, Veli-Matti; Heinonen, Seppo; Alitalo, Kari; Ylä-Herttuala, Seppo

    2013-03-01

    Abstract Antiangiogenic and antilymphangiogenic gene therapy with soluble vascular endothelial growth factor receptor-2 (VEGFR-2) and soluble VEGFR-3 in combination with chemotherapy is a potential new treatment for ovarian carcinoma. We evaluated the safety, toxicology, and biodistribution of intravenous AdsVEGFR-2 and AdsVEGFR-3 combined with chemotherapy in healthy rats (n=90) before entering a clinical setting. The study groups were: AdLacZ and AdLacZ with chemotherapy as control groups, low dose AdsVEGFR-2 and AdsVEGFR-3, high dose AdsVEGFR-2 and AdsVEGFR-3, combination of low dose AdsVEGFR-2 and AdsVEGFR-3 with chemotherapy, combination of high dose AdsVEGFR-2 and AdVEGFR-3 with chemotherapy, and chemotherapy only. The follow-up time was 4 weeks. Safety and toxicology were assessed by monitoring the clinical status of the animals and by histological, hematological, and clinical chemistry parameters. For the biodistribution studies, quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used. Low dose (2×10(10) vp) AdsVEGFR-2 and AdsVEGFR-3 gene therapy was well tolerated, even when gene therapy was combined with chemotherapy. Notably, only transient elevation of liver enzymes and mild regenerative changes were seen in liver after the gene transfer in the groups that received high doses (2×10(11) vp) of AdsVEGFR-2 and AdsVEGFR-3 with or without chemotherapy. No life-threatening adverse effects were noticed in any of the treatment groups. The highest protein concentration of soluble VEGFR-2 (sVEGFR-2) in circulation was seen 1 week after the gene transfer. The combination of chemotherapy to gene therapy seemed to prolong the time of detectable transgene protein at least 1 week in the circulation. The expression of AdsVEGFR-2 and AdsVEGFR-3 transgenes was mainly seen in the liver and spleen as detected by qRT-PCR. According to these results, AdsVEGFR-2 and AdsVEGFR-3 gene therapy combined with

  9. Preparation and biodistribution in mice of ( sup 11 C)carfentanil; A radiopharmaceutical for studying brain. mu. -opioid receptors by positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Saji, Hideo; Tsutsumi, Daisuke; Iida, Yasuhiko; Yokoyama, Akira (Kyoto Univ. (Japan). Faculty of Pharmaceutical Science); Magata, Yasuhiro; Konishi, Junji

    1992-02-01

    A potent {mu}-opioid agonist, ({sup 11}C)carfentanil, was prepared by the methylation of carfentanil carboxylic acid with ({sup 11}C)methyl iodide in order to study brain {mu}-opioid receptors by positron emission tomography. Synthesis (including purification) was completed within 25 min and the radiochemical yield was approximately 40%. The radiochemical purity of the product was more than 99% and its specific activity was 3.7-7.4 GBq/{mu}mol. Biodistribution studies performed in mice after intravenous injection showed a high brain uptake and rapid blood clearance, so a high brain/blood ratio of 1.5-1.8 was found from 5 to 30 min. Regional cerebral distribution studies in the mouse showed a significantly higher uptake of ({sup 11}C)carfentanil by the thalamus and striatum than by the cerebellum, with the radioactivity in the striatum disappearing more rapidly than that in the thalamus. Treatment with naloxone significantly reduced the uptake of ({sup 11}C)carfentanil by the thalamus and striatum. These results indicate that ({sup 11}C)carfentanil binds specifically to brain {mu}-opioid receptors. (author).

  10. Intranasal brain-targeted clonazepam polymeric micelles for immediate control of status epilepticus: in vitro optimization, ex vivo determination of cytotoxicity, in vivo biodistribution and pharmacodynamics studies.

    Science.gov (United States)

    Nour, Samia A; Abdelmalak, Nevine S; Naguib, Marianne J; Rashed, Hassan M; Ibrahim, Ahmed B

    2016-11-01

    Clonazepam (CZ) is an anti-epileptic drug used mainly in status epilepticus (SE). The drug belongs to Class II according to BCS classification with very limited solubility and high permeability and it suffers from extensive first-pass metabolism. The aim of the present study was to develop CZ-loaded polymeric micelles (PM) for direct brain delivery allowing immediate control of SE. PM were prepared via thin film hydration (TFH) technique adopting a central composite face-centered design (CCFD). The seventeen developed formulae were evaluated in terms of entrapment efficiency (EE), particle size (PS), polydispersity index (PDI), zeta potential (ZP), and in vitro release. For evaluating the in vivo behavior of the optimized formula, both biodistrbution using 99m Tc-radiolabeled CZ and pharmacodynamics studies were done in addition to ex vivo cytotoxicty. At a drug:Pluronic® P123:Pluronic® L121 ratio of 1:20:20 (PM7), a high EE, ZP, Q8h, and a low PDI was achieved. The biodistribution studies revealed that the optimized formula had significantly higher drug targeting efficiency (DTE = 242.3%), drug targeting index (DTI = 144.25), and nose-to-brain direct transport percentage (DTP = 99.30%) and a significant prolongation of protection from seizures in comparison to the intranasally administered solution with minor histopathological changes. The declared results reveal the ability of the developed PM to be a strong potential candidate for the emergency treatment of SE.

  11. Iodine-123 labelled nor-{beta}-CIT binds to the serotonin transporter in vivo as assessed by biodistribution studies in rats

    Energy Technology Data Exchange (ETDEWEB)

    Booij, J.; Knol, R.J.J.; Reneman, L.; De Bruin, K.; Van Royen, E.A. [Dept. of Nuclear Medicine, Univ. of Amsterdam (Netherlands); Janssen, A.G.M. [Amersham Cygne and Eindhoven University of Technology (Netherlands)

    1998-12-01

    Iodine-123 labelled 2{beta}-carbomethoxy-3{beta}-(4-iodophenyl)nortropane (nor-{beta}-CIT), a radioiodinated cocaine analogue, was evaluated as an agent for the in vivo labelling of serotonin transporters by biodistribution studies in rats. Intravenous injection of [{sup 123}I]nor-{beta}-CIT resulted in high accumulation of radioactivity in brain areas with high densities of serotonin (hypothalamus) and dopamine transporters (striatum), although the binding was less pronounced in the hypothalamus. While binding of [{sup 123}I]nor-{beta}-CIT in the hypothalamus was blocked significantly by fluvoxamine (a selective serotonin transporter blocker) but not by GBR12,909 (a selective dopamine transporter blocker), the opposite was observed in the striatum. The results of this study indicate that [{sup 123}I]nor-{beta}-CIT, although not being a selective radioligand, binds specifically to serotonin transporters in the hypothalamus in vivo and thus suggest that [{sup 123}I]nor-{beta}-CIT promises to be a suitable radioligand for single-photon emission tomography imaging of serotonin transporters in humans. (orig.) With 1 fig., 2 tabs., 15 refs.

  12. N-[11C]methyl-3,4-methylenedioxyamphetamine (Ecstasy) and 2-methyl-N-[11C]methyl-4,5-methylenedioxyamphetamine. Synthesis and biodistribution studies

    International Nuclear Information System (INIS)

    Patt, M.; Machulla, H.J.; Guendisch, D.; Kovar, K.A.; Wuellner, U.; Blocher, A.

    1999-01-01

    In order to evaluate the neurobiological mechanism causing the psychogenic effects of methylenedioxy-derivatives of amphetamine, the carbon-11 labeled analogues of 3,4-methylenedioxymethamphetamine (MDMA), 2 and 2,N-dimethyl-4,5-methylenedioxyamphetamine (MADAM-6) 4 were prepared for application in in-vivo PET studies by methylation of 3,4-methylenedioxyamphetamine (MDA) 1 and 2-methyl-4,5-methylenedioxyamphetamine 3 with [ 11 C]CH 3 I. The radiochemical yield was determined in dependence on time, temperature and amount of precursor. The best conditions for a fast labeling reaction with carbon-11 on a preparative scale were found to be a reaction time of 10 min using 1 mg of the corresponding dimethyl-precursors 1 or 3, thus obtaining radiochemical yields of 60% (based on produced [ 11 C]CH 3 I). Biodistribution studies were performed in rats, a high brain to blood ratio of 7.5 was observed for [ 11 C]MDMA in contrast to a ratio of 3.7 for [ 11 C]MADAM-6. (author)

  13. Iodine-123 labelled nor-β-CIT binds to the serotonin transporter in vivo as assessed by biodistribution studies in rats

    International Nuclear Information System (INIS)

    Booij, J.; Knol, R.J.J.; Reneman, L.; De Bruin, K.; Van Royen, E.A.; Janssen, A.G.M.

    1998-01-01

    Iodine-123 labelled 2β-carbomethoxy-3β-(4-iodophenyl)nortropane (nor-β-CIT), a radioiodinated cocaine analogue, was evaluated as an agent for the in vivo labelling of serotonin transporters by biodistribution studies in rats. Intravenous injection of [ 123 I]nor-β-CIT resulted in high accumulation of radioactivity in brain areas with high densities of serotonin (hypothalamus) and dopamine transporters (striatum), although the binding was less pronounced in the hypothalamus. While binding of [ 123 I]nor-β-CIT in the hypothalamus was blocked significantly by fluvoxamine (a selective serotonin transporter blocker) but not by GBR12,909 (a selective dopamine transporter blocker), the opposite was observed in the striatum. The results of this study indicate that [ 123 I]nor-β-CIT, although not being a selective radioligand, binds specifically to serotonin transporters in the hypothalamus in vivo and thus suggest that [ 123 I]nor-β-CIT promises to be a suitable radioligand for single-photon emission tomography imaging of serotonin transporters in humans. (orig.)

  14. IND-directed safety and biodistribution study of intravenously injected cetuximab-IRDye800 in cynomolgus macaques.

    Science.gov (United States)

    Zinn, Kurt R; Korb, Melissa; Samuel, Sharon; Warram, Jason M; Dion, David; Killingsworth, Cheryl; Fan, Jinda; Schoeb, Trenton; Strong, Theresa V; Rosenthal, Eben L

    2015-02-01

    The use of receptor-targeted antibodies conjugated to fluorophores is actively being explored for real-time imaging of disease states; however, the toxicity of the bioconjugate has not been assessed in non-human primates. To this end, the in vivo toxicity and pharmacokinetics of IRDye800 conjugated to cetuximab (cetuximab-IRDye800; 21 mg/kg; equivalent to 250 mg/m(2) human dose) were assessed in male cynomolgus monkeys over 15 days following intravenous injection and compared with an unlabeled cetuximab-dosed control group. Cetuximab-IRDye800 was well tolerated. There were no infusion reactions, adverse clinical signs, mortality, weight loss, or clinical histopathology findings. The plasma half-life for the cetuximab-IRDye800 and cetuximab groups was equivalent (2.5 days). The total recovered cetuximab-IRDye800 in all tissues at study termination was estimated to be 12 % of the total dose. Both cetuximab-IRDye800 and cetuximab groups showed increased QTc after dosing. The QTc for the cetuximab-dosed group returned to baseline by day 15, while the QTc of the cetuximab-IRDye800 remained elevated compared to baseline. IRDye800 in low molar ratios does not significantly impact cetuximab half-life or result in organ toxicity. These studies support careful cardiac monitoring (ECG) for human studies using fluorescent dyes.

  15. Toxicology and Biodistribution Studies for MGH2.1, an Oncolytic Virus that Expresses Two Prodrug-activating Genes, in Combination with Prodrugs

    Directory of Open Access Journals (Sweden)

    Kazue Kasai

    2013-01-01

    Full Text Available MGH2.1 is a herpes simplex virus type 1 (HSV1 oncolytic virus that expresses two prodrug-activating transgenes: the cyclophosphamide (CPA-activating cytochrome P4502B1 (CYP2B1 and the CPT11-activating secreted human intestinal carboxylesterase (shiCE. Toxicology and biodistribution of MGH2.1 in the presence/absence of prodrugs was evaluated in mice. MGH2.1 ± prodrugs was cytotoxic to human glioma cells, but not to normal cells. Pharmacokinetically, intracranial MGH2.1 did not significantly alter the metabolism of intraperitoneally (i.p. administered prodrugs in mouse plasma, brain, or liver. MGH2.1 did not induce an acute inflammatory reaction. MGH2.1 DNA was detected in brains of mice inoculated with 108 pfus for up to 60 days. However, only one animal showed evidence of viral gene expression at this time. Expression of virally encoded genes was restricted to brain. Intracranial inoculation of MGH2.1 did not induce lethality at 108 pfus in the absence of prodrugs and at 106 pfus in the presence of prodrugs. This study provides safety and toxicology data justifying a possible clinical trial of intratumoral injection of MGH2.1 with peripheral administration of CPA and/or CPT11 prodrugs in humans with malignant gliomas.

  16. Biodistribution Study of the Anaesthetic Sodium Phenobarbital Labelled with Technetium-99m in Swiss Mice Infected with Schistosoma mansoni Sambon, 1907

    Directory of Open Access Journals (Sweden)

    Susana Balmant Emerique Simões

    1997-09-01

    Full Text Available Technetium-99m (99mTc is a radionuclide that has negligible enviromnental impact, is easily available, inexpensive and can be used as a radioactive tracer in biological experiences. In order to know the mode of action of sodium phenobarbital in moving adult Schistosoma mansoni worms from mesenteric veins to the liver, we labelled sodium phenobarbital (PBBT with 99mTc and a biodistribution study in infected and non-infected Swiss mice was performed. The PBBT was incubated with stannous chloride used as reducing agent and with 99mTc, as sodium pertechnetate. The radioactivity labelling (% was determined by paper ascending chromatography perfomed with acetone (solvent. The 99mTc-PBBT was administered by intraperitoneal route to Swiss mice infected eight weeks before. The animals were perfused after diferent periods of time (0,1,2,3,4 hr when blood, spleen, liver, portal vein, mesenteric veins, stomach, kidneys and adult worms were isolated. The radioactivity present in these samples was counted in a well counter and the percentage was determined. The radioactivity was mainly taken up by the blood, kidney, liver and spleen. No radioactivity was found on the adult worms. We concluded that the worm shift was due to an action on the host of the sodium phenobarbital

  17. Clinical feasibility of {sup 90}Y digital PET/CT for imaging microsphere biodistribution following radioembolization

    Energy Technology Data Exchange (ETDEWEB)

    Wright, Chadwick L.; Binzel, Katherine; Zhang, Jun; Knopp, Michael V. [The Ohio State University Wexner Medical Center, Wright Center of Innovation in Biomedical Imaging, Department of Radiology, Columbus, OH (United States); Wuthrick, Evan J. [The Ohio State University Wexner Medical Center, Department of Radiation Oncology, Columbus, OH (United States)

    2017-07-15

    The purpose of this study was to evaluate the clinical feasibility of next generation solid-state digital photon counting PET/CT (dPET/CT) technology and imaging findings in patients following {sup 90}Y microsphere radioembolization in comparison with standard of care (SOC) bremsstrahlung SPECT/CT (bSPECT/CT). Five patients underwent SOC {sup 90}Y bremsstrahlung imaging immediately following routine radioembolization with 3.5 ± 1.7 GBq of {sup 90}Y-labeled glass microspheres. All patients also underwent dPET/CT imaging at 29 ± 11 h following radioembolization. Matched pairs comparison was used to compare image quality, image contrast and {sup 90}Y biodistribution between dPET/CT and bSPECT/CT images. Volumetric assessments of {sup 90}Y activity using different isocontour thresholds on dPET/CT and bSPECT/CT images were also compared. Digital PET/CT consistently provided better visual image quality and {sup 90}Y-to-background image contrast while depicting {sup 90}Y biodistribution than bSPECT/CT. Isocontour volumetric assessment using a 1% threshold precisely outlined {sup 90}Y activity and the treatment volume on dPET/CT images, whereas a more restrictive 20% threshold on bSPECT/CT images was needed to obtain comparable treatment volumes. The use of a less restrictive 10% threshold isocontour on bSPECT/CT images grossly overestimated the treatment volume when compared with the 1% threshold on dPET/CT images. Digital PET/CT is clinically feasible for the assessment of {sup 90}Y microsphere biodistribution following radioembolization, and provides better visual image quality and image contrast than routine bSPECT/CT with comparable acquisition times. With further optimization and clinical validation, dPET technology may allow faster and more accurate imaging-based assessment of {sup 90}Y microsphere biodistribution. (orig.)

  18. An experimental model to study the effects of a senna extract on the blood constituent labeling and biodistribution of a radiopharmaceutical in rats.

    Science.gov (United States)

    Souza, Deise Elizabeth; Pereira, Marcia Oliveira; Bernardo, Luciana Camargo; Carmo, Fernanda Santos; Fonseca, Adenilson de Souza da; Bernardo-Filho, Mario

    2011-01-01

    Cassia angustifolia Vahl (senna) is a natural product that contains sennosides, which are active components that affect the intestinal tract and induce diarrhea. Authors have shown that senna produces DNA (deoxyribonucleic acid) lesions in Escherichia coli cultures and can act as an antifungal agent. Natural drugs can alter the labeling of blood constituents with technetium-⁹⁹m (⁹⁹mTc) and can affect the biodistribution of radiopharmaceuticals. In this work, we have evaluated the influence of a senna extract on the radiolabeling of blood constituents and on the biodistribution of the radiopharmaceutical sodium pertechnetate (Na⁹⁹mTcO₄)in Wistar rats. Twelve animals were treated with senna extract for 7 days. Blood samples were withdrawn from the animals and the radiolabeling procedure was carried out. The senna extract did not modify the radiolabeling of the blood constituents. A biodistributional assay was performed by administering Na⁹⁹mTcO₄ and determining its activity in different organs and in blood. The senna extract altered the biodistribution of Na⁹⁹mTcO₄ in the thyroid, liver, pancreas, lungs and blood. These results are associated with properties of the chemical substances present in the aqueous senna extract. Although these assays were performed in animals, our findings suggest that caution should be exercised when nuclear medicine examinations using Na⁹⁹mTcO₄ are conducted in patients who are using senna extract.

  19. An experimental model to study the effects of a senna extract on the blood constituent labeling and biodistribution of a radiopharmaceutical in rats

    Directory of Open Access Journals (Sweden)

    Deise Elizabeth Souza

    2011-01-01

    Full Text Available Cassia angustifolia Vahl (senna is a natural product that contains sennosides, which are active components that affect the intestinal tract and induce diarrhea. Authors have shown that senna produces DNA (deoxyribonucleic acid lesions in Escherichia coli cultures and can act as an antifungal agent. Natural drugs can alter the labeling of blood constituents with technetium-99m (99mTc and can affect the biodistribution of radiopharmaceuticals. In this work, we have evaluated the influence of a senna extract on the radiolabeling of blood constituents and on the biodistribution of the radiopharmaceutical sodium pertechnetate (Na99mTcO4in Wistar rats. Twelve animals were treated with senna extract for 7 days. Blood samples were withdrawn from the animals and the radiolabeling procedure was carried out. The senna extract did not modify the radiolabeling of the blood constituents. A biodistributional assay was performed by administering Na99mTcO4 and determining its activity in different organs and in blood. The senna extract altered the biodistribution of Na99mTcO4 in the thyroid, liver, pancreas, lungs and blood. These results are associated with properties of the chemical substances present in the aqueous senna extract. Although these assays were performed in animals, our findings suggest that caution should be exercised when nuclear medicine examinations using Na99mTcO4 are conducted in patients who are using senna extract.

  20. An experimental model to study the effects of a senna extract on the blood constituent labeling and biodistribution of a radiopharmaceutical in rats

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Deise Elizabeth; Pereira, Marcia Oliveira; Bernardo, Luciana Camargo; Carmo, Fernanda Santos, E-mail: marciaoliveira.13@terra.com.b [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes. Lab. de Radiofarmacia Experimental; Fonseca, Adenilson de Souza da [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Inst. Biomedico. Dept. de Ciencias Fisiologicas; Bernardo-Filho, Mario [Instituto Nacional do Cancer (INCA), Rio de Janeiro, RJ (Brazil). Coordenadoria de Pesquisa

    2011-07-01

    Cassia angustifolia Vahl (senna) is a natural product that contains sennosides, which are active components that affect the intestinal tract and induce diarrhea. Authors have shown that senna produces DNA (deoxyribonucleic acid) lesions in Escherichia coli cultures and can act as an antifungal agent. Natural drugs can alter the labeling of blood constituents with technetium-99m ({sup 99m}Tc) and can affect the biodistribution of radiopharmaceuticals. In this work, we have evaluated the influence of a senna extract on the radiolabeling of blood constituents and on the biodistribution of the radiopharmaceutical sodium pertechnetate (Na{sup 99m}TcO{sub 4}) in Wistar rats. Twelve animals were treated with senna extract for 7 days. Blood samples were withdrawn from the animals and the radiolabeling procedure was carried out. The senna extract did not modify the radiolabeling of the blood constituents. A biodistributional assay was performed by administering Na{sup 99m}TcO{sub 4} and determining its activity in different organs and in blood. The senna extract altered the biodistribution of Na{sup 99m}TcO{sub 4} in the thyroid, liver, pancreas, lungs and blood. These results are associated with properties of the chemical substances present in the aqueous senna extract. Although these assays were performed in animals, our findings suggest that caution should be exercised when nuclear medicine examinations using Na{sup 99m}TcO{sub 4} are conducted in patients who are using senna extract. (author)

  1. An experimental model to study the effects of a senna extract on the blood constituent labeling and biodistribution of a radiopharmaceutical in rats

    International Nuclear Information System (INIS)

    Souza, Deise Elizabeth; Pereira, Marcia Oliveira; Bernardo, Luciana Camargo; Carmo, Fernanda Santos; Fonseca, Adenilson de Souza da; Bernardo-Filho, Mario

    2011-01-01

    Cassia angustifolia Vahl (senna) is a natural product that contains sennosides, which are active components that affect the intestinal tract and induce diarrhea. Authors have shown that senna produces DNA (deoxyribonucleic acid) lesions in Escherichia coli cultures and can act as an antifungal agent. Natural drugs can alter the labeling of blood constituents with technetium-99m ( 99m Tc) and can affect the biodistribution of radiopharmaceuticals. In this work, we have evaluated the influence of a senna extract on the radiolabeling of blood constituents and on the biodistribution of the radiopharmaceutical sodium pertechnetate (Na 99m TcO 4 ) in Wistar rats. Twelve animals were treated with senna extract for 7 days. Blood samples were withdrawn from the animals and the radiolabeling procedure was carried out. The senna extract did not modify the radiolabeling of the blood constituents. A biodistributional assay was performed by administering Na 99m TcO 4 and determining its activity in different organs and in blood. The senna extract altered the biodistribution of Na 99m TcO 4 in the thyroid, liver, pancreas, lungs and blood. These results are associated with properties of the chemical substances present in the aqueous senna extract. Although these assays were performed in animals, our findings suggest that caution should be exercised when nuclear medicine examinations using Na 99m TcO 4 are conducted in patients who are using senna extract. (author)

  2. Electrosteric stealth Rivastigmine loaded liposomes for brain targeting: preparation, characterization, ex vivo, bio-distribution and in vivo pharmacokinetic studies.

    Science.gov (United States)

    Nageeb El-Helaly, Sara; Abd Elbary, Ahmed; Kassem, Mohamed A; El-Nabarawi, Mohamed A

    2017-11-01

    Being one of the highly effective drugs in treatment of Alzheimer's disease, Rivastigmine brain targeting is highly demandable, therefore liposomal dispersion of Rivastigmine was prepared containing 2 mol% PEG-DSPE added to Lecithin, Didecyldimethyl ammonium bromide (DDAB), Tween 80 in 1:0.02:0.25 molar ratio. A major challenge during the preparation of liposomes is maintaining a stable formulation, therefore the aim of our study was to increase liposomal stability by addition of DDAB to give an electrostatic stability and PEG-DSPE to increase stability by steric hindrance, yielding what we called an electrosteric stealth (ESS) liposomes. A medium nano-sized liposome (478 ± 4.94 nm) with a nearly neutral zeta potential (ZP, -8 ± 0.2 mV) and an entrapment efficiency percentage of 48 ± 6.22 was prepared. Stability studies showed no major alteration after three months storage period concerning particle size, polydispersity index, ZP, entrapment efficiency and in vitro release study confirming the successful formation of a stable liposomes. No histopathological alteration was recorded for ESS liposomes of the sheep nasal mucosa. While ESS liposomes showed higher % of drug permeating through the sheep nasal mucosa (48.6%) than the drug solution (28.7%). On completing the in vivo pharmacokinetic studies of 36 rabbits showed 424.2% relative bioavailability of the mean plasma levels of the formula ESS compared to that of RHT intranasal solution and 486% relative bioavailability of the mean brain levels.

  3. Brain tumor magnetic targeting and biodistribution of superparamagnetic iron oxide nanoparticles linked with 70-kDa heat shock protein study by nonlinear longitudinal response

    International Nuclear Information System (INIS)

    Shevtsov, Maxim A.; Nikolaev, Boris P.; Ryzhov, Vyacheslav A.; Yakovleva, Ludmila Y.; Dobrodumov, Anatolii V.; Marchenko, Yaroslav Y.; Margulis, Boris A.; Pitkin, Emil; Guzhova, Irina V.

    2015-01-01

    Brain tumor targeting efficiency and biodistribution of the superparamagnetic nanoparticles conjugated with heat shock protein Hsp70 (SPION–Hsp70) were evaluated in experimental glioma model. Synthesized conjugates were characterized using the method of longitudinal nonlinear response of magnetic nanoparticles to a weak ac magnetic field with measurements of second harmonic of magnetization (NLR-M 2 ). Cellular interaction of magnetic conjugates was analyzed in 9L glioma cell culture. The biodistribution of the nanoparticles and their accumulation in tumors was assessed by the latter approach as well. The efficacy of Hsp70-conjugates for contrast enhancement in the orthotopic model of 9L glioma was assessed by MR imaging (11 T). Magnetic nanoparticles conjugated with Hsp70 had the relaxivity properties of the MR-negative contrast agents. Morphological observation and cell viability test demonstrated good biocompatibility of Hsp70-conjugates. Analysis of the T 2 -weighted MR scans in tumor-bearing rats demonstrated the high efficacy of Hsp70-conjugates in contrast enhancement of the glioma in comparison to non-conjugated nanoparticles. High contrast enhancement of the glioma was provided by the accumulation of the SPION–Hsp70 particles in the glioma tissue (as shown by the histological assay). Biodistribution analysis by NLR-M 2 measurements evidenced the many-fold increase (~40) in the tumor-to-normal brain uptake ratio in the Hsp70-conjugates treated animals. Biodistribution pattern of Hsp70-decorated nanoparticles differed from that of non-conjugated SPIONs. Coating of the magnetic nanoparticles with Hsp70 protein enhances the tumor-targeting ability of the conjugates that could be applied in the MR imaging of the malignant brain tumors. - Highlights: • Second-harmonic nonlinear magnetic response is used for biodistribution analysis. • NLR-M 2 ensures high sensibility in detection of SPIONs in tissue. • SPION–Hsp70 conjugates effectively target the

  4. Altered [99mTc]Tc-MDP biodistribution from neutron activation sourced 99Mo.

    Science.gov (United States)

    Demeter, Sandor; Szweda, Roman; Patterson, Judy; Grigoryan, Marine

    2018-01-01

    Given potential worldwide shortages of fission sourced 99 Mo/ 99m Tc medical isotopes there is increasing interest in alternate production strategies. A neutron activated 99 Mo source was utilized in a single center phase III open label study comparing 99m Tc, as 99m Tc Methylene Diphosphonate ([ 99m Tc]Tc-MDP), obtained from solvent generator separation of neutron activation produced 99 Mo, versus nuclear reactor produced 99 Mo (e.g., fission sourced) in oncology patients for which an [ 99m Tc]Tc-MDP bone scan would normally have been indicated. Despite the investigational [ 99m Tc]Tc-MDP passing all standard, and above standard of care, quality assurance tests, which would normally be sufficient to allow human administration, there was altered biodistribution which could lead to erroneous clinical interpretation. The cause of the altered biodistribution remains unknown and requires further research.

  5. Validation of 18FDG biodistribution data in healthy mice obtained with G.E. LABPET4

    International Nuclear Information System (INIS)

    Rocha, Adriana Marcia Guimaraes; Mendes, Bruno Melo; Malamut, Carlos; Silva, Juliana Batista da; Campos, Danielle Cunha; Santos, Priscilla Figueiredo

    2013-01-01

    The aim of this study is to validate biodistribution data obtained with CDTN's MicroPET. To achieve this goal, correction and image acquisition procedures were established. 1 '8FDG dynamic images of 90 minutes were obtained following these procedures for Swiss healthy mice. Biodistribution data obtained after quantification of acquired images were compared with data available in literature. Considering the uptake time of 60 minutes and similar animal handling, data obtained in this work showed a satisfactory agreement with reference data. Some evaluated organs/tissues showed high interindividual variability. These findings are consistent with those observed in reference literature. However, improvements in VOI positioning VOI technique as well as increasing the number of animals (n) per group can minimize this problem. (author)

  6. Effects of anesthetics on vesicular monoamine transporter type 2 binding to 18F-FP-(+)-DTBZ: a biodistribution study in rat brain

    International Nuclear Information System (INIS)

    Chen, Zhengping; Tang, Jie; Liu, Chunyi; Li, Xiaomin; Huang, Hongbo; Xu, Xijie; Yu, Huixin

    2016-01-01

    Objectives: The in vivo binding analysis of vesicular monoamine transporter type 2 (VMAT2) to radioligand has provided a means of investigating related disorders. Anesthesia is often inevitable when the investigations are performed in animals. In the present study, we tested effects of four commonly-used anesthetics: isoflurane, pentobarbital, chloral hydrate and ketamine, on in vivo VMAT2 binding to 18 F-FP-(+)-DTBZ, a specific VMAT2 radioligand, in rat brain. Methods: The transient equilibrium time window for in vivo binding of 18 F-FP-(+)-DTBZ after a bolus injection was firstly determined. The brain biodistribution studies under anesthetized and awake rats were then performed at the equilibrium time. Standard uptake values (SUVs) of the interest brain regions: the striatum (ST), hippocampus (HP), cortex (CX) and cerebellum (CB) were obtained; and ratios of tissue to cerebellum were calculated. Results: Isoflurane and pentobarbital did not alter distribution of 18 F-FP-(+)-DTBZ in the brain relative to the awake group; neither SUVs nor ratios of ST/CB and HP/CB were altered significantly. Chloral hydrate significantly increased SUVs of all the brain regions, but did not significantly alter ratios of ST/CB and HP/CB. Ketamine significantly increased SUVs of the striatum, hippocampus and cortex, and insignificantly increased the SUV of the cerebellum; consequently, ketamine significantly increased ratios of ST/CB and HP/CB. Conclusions: It is concluded that in vivo VMAT2 binding to 18 F-FP-(+)-DTBZ are not altered by isoflurane and pentobarbital, but altered by chloral hydrate and ketamine. Isoflurane and pentobarbital may be promising anesthetic compounds for investigating in vivo VMAT2 binding. Further studies are warranted to investigate the interactions of anesthetics with VMAT2 binding potential with in vivo PET studies.

  7. Whole-body biodistribution, dosimetry and metabolite correction of [11C]palmitate: A PET tracer for imaging of fatty acid metabolism

    DEFF Research Database (Denmark)

    Christensen, Nana Louise; Jakobsen, Steen; Schacht, Anna Christina

    2017-01-01

    INTRODUCTION: Despite the decades long use of [11C]palmitate positron emission tomography (PET)/computed tomography in basic metabolism studies, only personal communications regarding dosimetry and biodistribution data have been published. METHODS: Dosimetry and biodistribution studies were...... performed in 2 pigs and 2 healthy volunteers by whole-body [11C]palmitate PET scans. Metabolite studies were performed in 40 participants (healthy and with type 2 diabetes) under basal and hyperinsulinemic conditions. Metabolites were estimated using 2 approaches and subsequently compared: Indirect [11C]CO2...

  8. Studies of the radiolabeling and biodistribution of substance P using lutetium-177 as a radiotracer; Estudo da marcacao e biodistribuicao da substancia P utilizando lutecio-177 como radiotracador

    Energy Technology Data Exchange (ETDEWEB)

    Lima, Clarice Maria de

    2011-07-01

    -DOTA-SP, radiolabeled in the absence and presence of methionine, using human M059J U-87 MG glioma cells and, showed the effect of oxidation of methionine on the cells binding. Biodistribution studies were performed in Nude mice with tumor model and Balb-c mice. Highest radiochemical purity (> 95%) associated with the highest specific activity of '1{sup 77}Lu-DOTA-SP when the reaction time was 30 minutes, temperature of 90 degree C, 10 g{mu} of DOTA-SP, and the activity of {sup 177}Lu of 185 MBq. The radiolabeled SP in optimized conditions remained stable at 2-8 degree C and in human serum for 4 hours. In vitro studies showed the binding to cell receptors and this binding was reduced when the peptide was presented in its oxidized form. The addition of methionine combined with gentisic acid prevented the oxidation of peptide and increased the stability of the labeled compound, particularly with high activity of {sup 177}Lu, when using larger mass of DOTA-SP. In vivo studies results showed a favorable biodistribution kinetics of the compound and ability to bind to tumor cells. {sup 177}Lu-DOTA-SP can be a useful tool for in vivo studies due to ease preparation, high stability and affinity for tumor cells. (author)

  9. Two anti-angiogenic TKI-PET tracers, [11C]axitinib and [11C]nintedanib: Radiosynthesis, in vivo metabolism and initial biodistribution studies in rodents

    International Nuclear Information System (INIS)

    Slobbe, Paul; Poot, Alex J.; Haumann, Rianne; Schuit, Robert C.; Windhorst, Albert D.; Dongen, Guus A.M.S. van

    2016-01-01

    Introduction: Tyrosine kinase inhibitors (TKIs) are very attractive targeted drugs, although a large portion of patients remains unresponsive. PET imaging with EGFR targeting TKIs ([ 11 C]erlotinib and [ 18 F]afatinib) showed promise in identifying treatment sensitive tumors. The aim of this study was to synthesize two anti-angiogenic TKI tracers, [ 11 C]axitinib and [ 11 C]nintedanib, and to evaluate their potential for PET. Methods: Following successful tracer synthesis, biodistribution studies in VU-SCC-OE and FaDu xenograft bearing mice were performed. Furthermore, tracer stability studies in mice were performed employing (radio-)HPLC and LC–MS/MS techniques. For [ 11 C]nintedanib an LC–MS/MS method was developed to detect the primary carboxylic acid metabolite, resulting from methylester cleavage, in plasma and tumors, because this metabolite is postulated to be important for nintedanib efficacy. LC–MS/MS was also explored to assess the metabolic fate of [ 11 C]axitinib in vivo, since axitinib has an isomerizable double bond. Results: [ 11 C]axitinib and [ 11 C]nintedanib were successfully synthesized with 10.5 ± 2.6% and 25.6 ± 3.3% radiochemical yield (corrected for decay), respectively. Biodistribution studies only demonstrated tumor uptake of [ 11 C]nintedanib in FaDu xenografts of 1.66 ± 0.02% ID/g at 60 min p.i. In vivo stability analysis of [ 11 C]axitinib at 45 min p.i. revealed the formation of predominantly non-polar metabolites (36.6 ± 6.8% vs 47.1 ± 8.4% of parent tracer and 16.3 ± 2.1% of polar metabolites), while for [ 11 C]nintedanib mostly polar metabolites were found (70.9 ± 4.1 vs 26.7 ± 3.9% of parent tracer and only 2.4 ± 1.6 of a non-polar metabolites). No isomerization of [ 11 C]axtinib was observed in vivo; however, a sulfoxide metabolite could be detected using LC–MS/MS. For [ 11 C]nintedanib, LC–MS/MS revealed formation of the reported primary carboxylic acid metabolite when in vitro plasma incubations were performed

  10. Comparative Studies for What?

    Directory of Open Access Journals (Sweden)

    Pedro Guedes de Carvalho

    2017-12-01

    Full Text Available ISCPES stands for International Society for Comparative Physical Education and Sports and it is going to celebrate its 40th anniversary in 2018. Since the beginning (Israel 1978 the main goals of the Society were established under a worldwide mind set considering five continents and no discrimination of any kind. The founders wanted to compare Physical Education and Sports across the world, searching for the best practices deserving consideration and applied on the purpose of improving citizen quality of life. The mission still stands for “Compare to learn and improve”. As all the organizations lasting for 39 years, ISCPES experienced several vicissitudes, usually correlated with world economic cycles, social and sports changes, which are in ISS journal articles - International Sport Studies. ISS journal is Scopus indexed, aiming to improve its quality (under evaluation to reach more qualified students, experts, professionals and researchers; doing so it will raise its indexation, which we know it is nowadays a more difficult task. First, because there are more journals trying to compete on this academic fierce competitive market; secondly, because the basic requirements are getting more and more hard to gather in the publishing environment around Physical Education and Sports issues. However, we can promise this will be one of our main strategic goals. Another goal I would like to address on this Editorial is the language issue. We have this second strategic goal, which is to reach most of languages spoken in different continents; besides the English language, we will reach Chinese, Spanish and Portuguese speaking countries. For that reason, we already defined that all the abstracts in English will be translated into Chinese, Spanish and Portuguese words so people can find them on any search browser. That will expand the demand for our journal and articles, increasing the number of potential readers. Of course this opportunity, given by

  11. Whole-body biodistribution, dosimetry and metabolite correction of [11C]palmitate: A PET tracer for imaging of fatty acid metabolism

    DEFF Research Database (Denmark)

    Christensen, Nana Louise; Jakobsen, Steen; Schacht, Anna Christina

    2017-01-01

    release and parent [11C]palmitate measured by a solid-phase extraction (SPE) method. Finally, myocardial fatty acid uptake was calculated in a patient cohort using input functions derived from individual metabolite correction compared with population-based metabolite correction. RESULTS: In humans, mean......INTRODUCTION: Despite the decades long use of [11C]palmitate positron emission tomography (PET)/computed tomography in basic metabolism studies, only personal communications regarding dosimetry and biodistribution data have been published. METHODS: Dosimetry and biodistribution studies were...

  12. Operations dashboard: comparative study

    Science.gov (United States)

    Ramly, Noor Nashriq; Ismail, Ahmad Zuhairi; Aziz, Mohd Haris; Ahmad, Nurul Haszeli

    2011-10-01

    In this present days and age, there are increasing needs for companies to monitor application and infrastructure health. Apart from having proactive measures to secure their application and infrastructure, many see monitoring dashboards as crucial investment in disaster preparedness. As companies struggle to find the best solution to cater for their needs and interest for monitoring their application and infrastructure's health, this paper summarizes the studies made on several known off-the-shelf operations dashboard and in-house developed dashboard. A few criteria of good dashboard are collected from previous studies carried out by several researchers and rank them according to importance and business needs. The finalized criteria that will be discussed in later sections are data visualization, performance indicator, dashboard personalization, audit capability and alert/ notification. Comparative studies between several popular dashboards were then carried out to determine whether they met these criteria that we derived from the first exercise. The findings hopefully can be used to educate and provide an overview of selecting the best IT application and infrastructure operations dashboard that suit business needs, thus become the main contribution of this paper.

  13. Quantitative cumulative biodistribution of antibodies in mice

    Science.gov (United States)

    Yip, Victor; Palma, Enzo; Tesar, Devin B; Mundo, Eduardo E; Bumbaca, Daniela; Torres, Elizabeth K; Reyes, Noe A; Shen, Ben Q; Fielder, Paul J; Prabhu, Saileta; Khawli, Leslie A; Boswell, C Andrew

    2014-01-01

    The neonatal Fc receptor (FcRn) plays an important and well-known role in antibody recycling in endothelial and hematopoietic cells and thus it influences the systemic pharmacokinetics (PK) of immunoglobulin G (IgG). However, considerably less is known about FcRn’s role in the metabolism of IgG within individual tissues after intravenous administration. To elucidate the organ distribution and gain insight into the metabolism of humanized IgG1 antibodies with different binding affinities FcRn, comparative biodistribution studies in normal CD-1 mice were conducted. Here, we generated variants of herpes simplex virus glycoprotein D-specific antibody (humanized anti-gD) with increased and decreased FcRn binding affinity by genetic engineering without affecting antigen specificity. These antibodies were expressed in Chinese hamster ovary cell lines, purified and paired radiolabeled with iodine-125 and indium-111. Equal amounts of I-125-labeled and In-111-labeled antibodies were mixed and intravenously administered into mice at 5 mg/kg. This approach allowed us to measure both the real-time IgG uptake (I-125) and cumulative uptake of IgG and catabolites (In-111) in individual tissues up to 1 week post-injection. The PK and distribution of the wild-type IgG and the variant with enhanced binding for FcRn were largely similar to each other, but vastly different for the rapidly cleared low-FcRn-binding variant. Uptake in individual tissues varied across time, FcRn binding affinity, and radiolabeling method. The liver and spleen emerged as the most concentrated sites of IgG catabolism in the absence of FcRn protection. These data provide an increased understanding of FcRn’s role in antibody PK and catabolism at the tissue level. PMID:24572100

  14. Dosimetric estimation of O-(3-18F-fluoropropyl)-L-tyrosine in human based on mice biodistribution data

    International Nuclear Information System (INIS)

    Tang Ganghua; Wang Mingfang; Luo Lei; Gan Manquan; Tang Xiaolan

    2002-01-01

    Objective: To estimate the radiation absorbed doses in humans due to intravenous administration of O-(3- 18 F-fluoropropyl)-L-tyrosine (FPT) based on mice biodistribution data and appraise the security of FPT in humans. Methods: FPT was injected into mice through a tail vein. At 10, 30, 60, 120 and 180 min after injection, the mice were killed by cervical fracture and biodistribution in mice were determined. Human dosimetric estimation was performed from the biodistribution of FPT in mice and the standard MIRD method using fractional radioactivity-time curves for humans. Results: The bone in human was the organ receiving highest dose of 4.29 x 10 -3 mGy/MBq, the brain received lowest dose of 1.57 x 10 -3 mGy/MBq, and other organs received doses between 1.8 x 10 -3 and 2.4 x 10 -3 mGy/MBq. The effective dose was estimated to be 9.15 x 10 -3 mSv/MBq. These results were comparable to values reported by foreign authors on the radiation dosimetry of O-(2- 18 F-fluoroethyl)-L-tyrosine. Conclusion: Human dosimetric estimation can be performed based on mice biodistribution data. The study provides an important data for clinical safety of FPT

  15. Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting

    Directory of Open Access Journals (Sweden)

    Oscar P. B. Wiklander

    2015-04-01

    Full Text Available Extracellular vesicles (EVs have emerged as important mediators of intercellular communication in a diverse range of biological processes. For future therapeutic applications and for EV biology research in general, understanding the in vivo fate of EVs is of utmost importance. Here we studied biodistribution of EVs in mice after systemic delivery. EVs were isolated from 3 different mouse cell sources, including dendritic cells (DCs derived from bone marrow, and labelled with a near-infrared lipophilic dye. Xenotransplantation of EVs was further carried out for cross-species comparison. The reliability of the labelling technique was confirmed by sucrose gradient fractionation, organ perfusion and further supported by immunohistochemical staining using CD63-EGFP probed vesicles. While vesicles accumulated mainly in liver, spleen, gastrointestinal tract and lungs, differences related to EV cell origin were detected. EVs accumulated in the tumour tissue of tumour-bearing mice and, after introduction of the rabies virus glycoprotein-targeting moiety, they were found more readily in acetylcholine-receptor-rich organs. In addition, the route of administration and the dose of injected EVs influenced the biodistribution pattern. This is the first extensive biodistribution investigation of EVs comparing the impact of several different variables, the results of which have implications for the design and feasibility of therapeutic studies using EVs.

  16. Tissue-specific Calibration of Real-time PCR Facilitates Absolute Quantification of Plasmid DNA in Biodistribution Studies

    Directory of Open Access Journals (Sweden)

    Joan K Ho

    2016-01-01

    Full Text Available Analysis of the tissue distribution of plasmid DNA after administration of nonviral gene delivery systems is best accomplished using quantitative real-time polymerase chain reaction (qPCR, although published strategies do not allow determination of the absolute mass of plasmid delivered to different tissues. Generally, data is expressed as the mass of plasmid relative to the mass of genomic DNA (gDNA in the sample. This strategy is adequate for comparisons of efficiency of delivery to a single site but it does not allow direct comparison of delivery to multiple tissues, as the mass of gDNA extracted per unit mass of each tissue is different. We show here that by constructing qPCR standard curves for each tissue it is possible to determine the dose of intact plasmid remaining in each tissue, which is a more useful parameter when comparing the fates of different formulations of DNA. We exemplify the use of this tissue-specific qPCR method by comparing the delivery of naked DNA, cationic DNA complexes, and neutral PEGylated DNA complexes after intramuscular injection. Generally, larger masses of intact plasmid were present 24 hours after injection of DNA complexes, and neutral complexes resulted in delivery of a larger mass of intact plasmid to the spleen.

  17. Biodistribution of 99Mo in rats

    International Nuclear Information System (INIS)

    Souza, Raphael Sancho Sisley de; Ribeiro, Bianca da Silva; Dantas, Ana Leticia Almeida; Dantas, Bernardo Maranhao; Bernardo Filho, Mario

    2009-01-01

    The modification of 99 Mo standard metabolism in the presence of MDP would alter the dosimetry of this radionuclide in nuclear medicine patients. Therefore, the objective of this work is to evaluate the influence of MDP in the biodistribution of 99 Mo. Wistar rats were divided in two groups of six animals, being inoculated respectively 99 Molibdate and 99 Mo+MDP via plex ocular. The biodistribution study was carried out after 10 and 120 minutes respectively. The organs were counted with a NaI(Tl) detector. The uptake values did not present significant differences among the groups. An in vitro study through planar chromatography was carried out to determine the affinity between molybdenum and MDP. The results show that 99 Mo has low affinity both to propanone and NaCl-0.9% solution. However, 99 Mo in the presence of MDP presented affinity to NaCl-0.9% solution and low affinity to propanone suggesting that 99 Mo was bound to MDP under the conditions of the experiment. (author)

  18. Binding Affinity, Specificity and Comparative Biodistribution of the Parental Murine Monoclonal Antibody MX35 (Anti-NaPi2b) and Its Humanized Version Rebmab200

    DEFF Research Database (Denmark)

    Lindegren, Sture; Andrade, Luciana N S; Bäck, Tom

    2015-01-01

    The aim of this preclinical study was to evaluate the characteristics of the monoclonal antibody Rebmab200, which is a humanized version of the ovarian-specific murine antibody MX35. This investigation contributes to the foundation for future clinical α-radioimmunotherapy of minimal residual...

  19. Comparative waste forms study

    International Nuclear Information System (INIS)

    Wald, J.W.; Lokken, R.O.; Shade, J.W.; Rusin, J.M.

    1980-12-01

    A number of alternative process and waste form options exist for the immobilization of nuclear wastes. Although data exists on the characterization of these alternative waste forms, a straightforward comparison of product properties is difficult, due to the lack of standardized testing procedures. The characterization study described in this report involved the application of the same volatility, mechanical strength and leach tests to ten alternative waste forms, to assess product durability. Bulk property, phase analysis and microstructural examination of the simulated products, whose waste loading varied from 5% to 100% was also conducted. The specific waste forms investigated were as follows: Cold Pressed and Sintered PW-9 Calcine; Hot Pressed PW-9 Calcine; Hot Isostatic Pressed PW-9 Calcine; Cold Pressed and Sintered SPC-5B Supercalcine; Hot Isostatic pressed SPC-5B Supercalcine; Sintered PW-9 and 50% Glass Frit; Glass 76-68; Celsian Glass Ceramic; Type II Portland Cement and 10% PW-9 Calcine; and Type II Portland Cement and 10% SPC-5B Supercalcine. Bulk property data were used to calculate and compare the relative quantities of waste form volume produced at a spent fuel processing rate of 5 metric ton uranium/day. This quantity ranged from 3173 L/day (5280 Kg/day) for 10% SPC-5B supercalcine in cement to 83 L/day (294 Kg/day) for 100% calcine. Mechanical strength, volatility, and leach resistance tests provide data related to waste form durability. Glass, glass-ceramic and supercalcine ranked high in waste form durability where as the 100% PW-9 calcine ranked low. All other materials ranked between these two groupings

  20. Brain-targeted solid lipid nanoparticles containing riluzole: preparation, characterization and biodistribution.

    Science.gov (United States)

    Bondì, Maria Luisa; Craparo, Emanuela Fabiola; Giammona, Gaetano; Drago, Filippo

    2010-01-01

    Developments within nanomedicine have revealed a great potential for drug delivery to the brain. In this study nanoparticulate systems as drug carriers for riluzole, with sufficiently high loading capacity and small particle size, were prepared to a reach therapeutic drug level in the brain. Solid lipid nanoparticles containing riluzole have great potential as drug-delivery systems for amyotrophic lateral sclerosis and were produced by using the warm oil-in-water microemulsion technique. The resulting systems obtained were approximately 88 nm in size and negatively charged. Drug-release profiles demonstrated that a drug release was dependent on medium pH. Biodistribution of riluzole blended into solid lipid nanoparticles was carried out after administration to rats and the results were compared with those obtained by riluzole aqueous dispersion administration. Rats were sacrificed at time intervals of 8, 16 and 30 h, and the riluzole concentration in the blood and organs such as the brain, liver, spleen, heart and kidney was determined. It was demonstrated that these solid lipid nanoparticles were able to successfully carry riluzole into the CNS. Moreover, a low drug biodistribution in organs such as the liver, spleen, heart, kidneys and lung was found when riluzole was administered as drug-loaded solid lipid nanoparticles. Riluzole-loaded solid lipid nanoparticles showed colloidal size and high drug loading, a greater efficacy than free riluzole in rats, a higher capability to carry the drug into the brain and a lower indiscriminate biodistribution.

  1. Investigations of a new, highly negative liposome with improved biodistribution for imaging

    International Nuclear Information System (INIS)

    Hnatowich, D.J.; Clancy, B.

    1980-01-01

    An attractive feature of liposomes is the wide range of lipid composition that can lead to liposome formation, coupled with the observation that liposome biodistribution may be altered by varying lipid composition. For instance, adding charged lipids to neutral lecithin will alter the biodistribution of the resulting charged liposomes. We have prepared highly negative liposomes by replacing lecithin with negatively charged cardiolipin. The liposomes have been labeled in the lipid phase with Ga-67 and Tc-99m oxine and their properties evaluated. The expected high negative charge of the resulting liposomes was confirmed by an ion-exchange chromatographic technique. Using paper chromatography, the stability of the label was determined during incubation in saline and serum. Finally, biodistributions were determined at 2 h in mice, and the results compared with those for negative lecithin liposomes. Accumulated activities in liver and spleen were reduced by factors of five and 20, respectively, over lecithin liposomes. Since preferential accumulation of activity in these organs constitutes the biggest limitation to the use of lecithin liposomes, cardiolipin liposomes may prove to be more useful carriers of radioactivity in imaging applications. More importantly, however, these results illustrate the value of studying novel liposome types as potential radiopharmaceuticals

  2. Combined chelation based on glycosyl-mono- and bis-hydroxypyridinones for aluminium mobilization: solution and biodistribution studies.

    Science.gov (United States)

    Chaves, Sílvia; Dron, Paul I; Danalache, Florina A; Sacoto, Diana; Gano, Lurdes; Santos, M Amélia

    2009-11-01

    Taking into account the recognized interest of a poly-pharmacological strategy in chelation therapy, a study of aluminium combined chelation based on 3-hydroxy-4-pyridinone (3,4-HP) compounds with complementary properties, associated to different denticity, size and extrafunctionality, is presented herein. In particular, Al-chelation has been explored, using a tetradentate IDA bis-(3,4-HP) ligand, L, and two N-glycosyl mono-(3,4-HP) derivatives (A or B). Combined complexation studies with the tetradentate and the most promising bidentate ligand (A) evidenced the formation of ternary complexes with high thermodynamic stability (Al-L-A) being the predominant species at physiological pH. In vivo studies on the ability for radiotracer ((67)Ga) removal from loaded mice, as a model of aluminium accumulation in body, have shown that the simultaneous administration to (67)Ga-loaded mice of a mono- and a bis-(3,4-HP) chelator (e.g. A and L) leads to a rapid metal elimination from main organs and whole animal model. This may be rationalized by coadjuvation and eventual synergistic effects, due to complementary accessibility of the chelators to different cellular compartments.

  3. Brain tumor magnetic targeting and biodistribution of superparamagnetic iron oxide nanoparticles linked with 70-kDa heat shock protein study by nonlinear longitudinal response

    Energy Technology Data Exchange (ETDEWEB)

    Shevtsov, Maxim A., E-mail: shevtsov-max@mail.ru [Institute of Cytology of the Russian Academy of Sciences (RAS), Tikhoretsky Ave. 4, St. Petersburg 194064 (Russian Federation); A.L. Polenov Russian Research Scientific Institute of Neurosurgery, Mayakovsky str. 12, St. Petersburg 191014 (Russian Federation); Nikolaev, Boris P. [Research Institute of Highly Pure Biopreparations, Pudozhskaya str. 12, St. Petersburg 197110 (Russian Federation); Ryzhov, Vyacheslav A. [Petersburg Nuclear Physics Institute, NRC Kurchatov Institute, Gatchina 188300 (Russian Federation); Yakovleva, Ludmila Y. [Research Institute of Highly Pure Biopreparations, Pudozhskaya str. 12, St. Petersburg 197110 (Russian Federation); Dobrodumov, Anatolii V. [Institute of Macromolecular Compounds of the Russian Academy of Sciences (RAS), Bolshoi pr. 31, St. Petersburg 199004 (Russian Federation); Marchenko, Yaroslav Y. [Research Institute of Highly Pure Biopreparations, Pudozhskaya str. 12, St. Petersburg 197110 (Russian Federation); Margulis, Boris A. [Institute of Cytology of the Russian Academy of Sciences (RAS), Tikhoretsky Ave. 4, St. Petersburg 194064 (Russian Federation); Pitkin, Emil [The Wharton School, University of Pennsylvania, 3730 Walnut St., Philadelphia, PA 19104 (United States); Guzhova, Irina V. [Institute of Cytology of the Russian Academy of Sciences (RAS), Tikhoretsky Ave. 4, St. Petersburg 194064 (Russian Federation)

    2015-08-15

    Brain tumor targeting efficiency and biodistribution of the superparamagnetic nanoparticles conjugated with heat shock protein Hsp70 (SPION–Hsp70) were evaluated in experimental glioma model. Synthesized conjugates were characterized using the method of longitudinal nonlinear response of magnetic nanoparticles to a weak ac magnetic field with measurements of second harmonic of magnetization (NLR-M{sub 2}). Cellular interaction of magnetic conjugates was analyzed in 9L glioma cell culture. The biodistribution of the nanoparticles and their accumulation in tumors was assessed by the latter approach as well. The efficacy of Hsp70-conjugates for contrast enhancement in the orthotopic model of 9L glioma was assessed by MR imaging (11 T). Magnetic nanoparticles conjugated with Hsp70 had the relaxivity properties of the MR-negative contrast agents. Morphological observation and cell viability test demonstrated good biocompatibility of Hsp70-conjugates. Analysis of the T{sub 2}-weighted MR scans in tumor-bearing rats demonstrated the high efficacy of Hsp70-conjugates in contrast enhancement of the glioma in comparison to non-conjugated nanoparticles. High contrast enhancement of the glioma was provided by the accumulation of the SPION–Hsp70 particles in the glioma tissue (as shown by the histological assay). Biodistribution analysis by NLR-M{sub 2} measurements evidenced the many-fold increase (~40) in the tumor-to-normal brain uptake ratio in the Hsp70-conjugates treated animals. Biodistribution pattern of Hsp70-decorated nanoparticles differed from that of non-conjugated SPIONs. Coating of the magnetic nanoparticles with Hsp70 protein enhances the tumor-targeting ability of the conjugates that could be applied in the MR imaging of the malignant brain tumors. - Highlights: • Second-harmonic nonlinear magnetic response is used for biodistribution analysis. • NLR-M{sub 2} ensures high sensibility in detection of SPIONs in tissue. • SPION–Hsp70 conjugates

  4. Study of labeling, biodistribution and scintilographic images in dog of the 15-p- iodophenyl pentadecanoic acid labeling with 131I

    International Nuclear Information System (INIS)

    Oliveira, Ione Caselato

    1997-01-01

    The myocardium scintigraphy obtained after a radioactive tracer administration is a way to identify and quantify ischemic or infarct areas. The acid 15-p-iodophenyl pentadecanoic is marked with 131 I (IPPA - 131 I), through the isotopic exchange methodology in copper sulfate and ascorbic acid presence. The radiochemical purity will be evaluated by high performance liquid chromatography (HPLC) and rising chromatography in paper. The optimization of the mark conditions was done by varying time and marking temperatures where it was shown considerable mark revenue with high radiochemical purity at 120 deg C in 30 minutes. The marked mixture stays stable up the seventh day after marking. In the biological distribution studies is observed that right after the intravenous administration of the IPPA - 131 I it is achieved a considerable capitation by the cardiac muscle. The radiopharmaceutical displays a fast blood metabolizing. The scintigraphy images obtained in dogs indicates that there is a stay in heart, allowing the identification of the cardiac muscle. (author)

  5. Biodistribution patterns of native and mutant 99mTc-labelled annexin V in mice

    International Nuclear Information System (INIS)

    Mariani, G.; Erba, P.; Pellegrino, D.; Volterrani, D.; Lazzeri, E.; Freer, G.; Bevilacqua, G.; Blankenberg, F.G.; Tait, J.F.; Strauss, H.W.

    2003-01-01

    Full text: Annexin is a 36 kD protein with high binding affinity to phosphatidylserine (PS), a phospholipid exposed on the membrane surface of cells upon activation of the enzyme caspase, the first step of apoptosis. Radiolabeled annexin V could thus be used for imaging apoptosis in-vivo. When the 319 amino acid protein is made by recombinant techniques and expressed as the human material, it can be radiolabeled with 99mTc after derivatization with a bifunctional agent such as HYNIC. Alternatively, the amino acid structure of the protein can be modified by producing annexin V mutants with an endogenous chelation site for 99mTc, the NH2 residue Ala-Gly-Gly-Cys-Gly-His-Met. Mutant annexin has similar affinity for membrane-bound PS as unmodified annexin. This study was performed to compare the biodistribution of 99mTc-labeled HYNIC annexin (HyA) to mutant annexin (MuA). 99mTc-labeling efficiency of the two annexin preparations was >99% by gel chromatography on Sephadex G10 columns. Groups of adult male mice (n 10, body weight 18-25 grams) were injected iv with either HyA or MuA (1-3 MBq, 3-9 μg/animal). Animals were sacrificed one hour later and dissected for organ biodistribution. Similar biodistribution was performed after pretreatment with cyclophosphamide (150 mg/kg ip 6-15 hr prior to the study). The results of the biodistribution study showed significantly reduced (p<0.05 to p<0.01) uptake of MuA versus HyA in the kidneys (Δ- 81.4%), spleen (Δ- 58.2%), liver (Δ- 56.2%), and bone marrow (Δ- 33.7%), while it was increased in lymph nodes (Δ+ 131%, p<0.001). Pretreatment with the pro-apoptotic agent cyclophosphamide induced significantly increased uptake of MuA (p<0.05) versus baseline in the heart (Δ+ 34.7%), spleen (Δ+ 30.1%) and bowel (Δ+ 44.5%), while uptake of HyA was increased only in the spleen (Δ+ 44.1%). The marked reduction in the renal, splenic, liver, and bone marrow localization of MuA compared to HyA in control animals outlines a pattern of

  6. Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential

    International Nuclear Information System (INIS)

    Nigg, David W.

    2012-01-01

    Boron neutron capture therapy (BNCT) combines selective accumulation of 10B carriers in tumor tissue with subsequent neutron irradiation. We previously demonstrated the therapeutic efficacy of BNCT in the hamster cheek pouch oral cancer model. Optimization of BNCT depends largely on improving boron targeting to tumor cells. Seeking to maximize the potential of BNCT for the treatment for head and neck cancer, the aim of the present study was to perform boron biodistribution studies in the oral cancer model employing two different liposome formulations that were previously tested for a different pathology, i.e., in experimental mammary carcinoma in BALB/c mice: (1) MAC: liposomes incorporating K(nido-7-CH3(CH2)15-7,8-C2B9H11) in the bilayer membrane and encapsulating a hypertonic buffer, administered intravenously at 6 mg B per kg body weight, and (2) MAC-TAC: liposomes incorporating K(nido-7-CH3(CH2)15-7,8-C2B9H11) in the bilayer membrane and encapsulating a concentrated aqueous solution of the hydrophilic species Na3 (ae-B20H17NH3), administered intravenously at 18 mg B per kg body weight. Samples of tumor, precancerous and normal pouch tissue, spleen, liver, kidney, and blood were taken at different times post-administration and processed to measure boron content by inductively coupled plasma mass spectrometry. No ostensible clinical toxic effects were observed with the selected formulations. Both MAC and MAC-TAC delivered boron selectively to tumor tissue. Absolute tumor values for MAC-TAC peaked to 66.6 ± 16.1 ppm at 48 h and to 43.9 ± 17.6 ppm at 54 h with very favorable ratios of tumor boron relative to precancerous and normal tissue, making these protocols particularly worthy of radiobiological assessment. Boron concentration values obtained would result in therapeutic BNCT doses in tumor without exceeding radiotolerance in precancerous/normal tissue at the thermal neutron facility at RA-3.

  7. Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential

    Energy Technology Data Exchange (ETDEWEB)

    David W. Nigg

    2012-05-01

    Boron neutron capture therapy (BNCT) combines selective accumulation of 10B carriers in tumor tissue with subsequent neutron irradiation. We previously demonstrated the therapeutic efficacy of BNCT in the hamster cheek pouch oral cancer model. Optimization of BNCT depends largely on improving boron targeting to tumor cells. Seeking to maximize the potential of BNCT for the treatment for head and neck cancer, the aim of the present study was to perform boron biodistribution studies in the oral cancer model employing two different liposome formulations that were previously tested for a different pathology, i.e., in experimental mammary carcinoma in BALB/c mice: (1) MAC: liposomes incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer membrane and encapsulating a hypertonic buffer, administered intravenously at 6 mg B per kg body weight, and (2) MAC-TAC: liposomes incorporating K[nido-7-CH3(CH2)15-7,8-C2B9H11] in the bilayer membrane and encapsulating a concentrated aqueous solution of the hydrophilic species Na3 [ae-B20H17NH3], administered intravenously at 18 mg B per kg body weight. Samples of tumor, precancerous and normal pouch tissue, spleen, liver, kidney, and blood were taken at different times post-administration and processed to measure boron content by inductively coupled plasma mass spectrometry. No ostensible clinical toxic effects were observed with the selected formulations. Both MAC and MAC-TAC delivered boron selectively to tumor tissue. Absolute tumor values for MAC-TAC peaked to 66.6 {+-} 16.1 ppm at 48 h and to 43.9 {+-} 17.6 ppm at 54 h with very favorable ratios of tumor boron relative to precancerous and normal tissue, making these protocols particularly worthy of radiobiological assessment. Boron concentration values obtained would result in therapeutic BNCT doses in tumor without exceeding radiotolerance in precancerous/normal tissue at the thermal neutron facility at RA-3.

  8. Dendrimers: relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labelled polyamidoamine dendrimers in vivo.

    Science.gov (United States)

    Malik, N; Wiwattanapatapee, R; Klopsch, R; Lorenz, K; Frey, H; Weener, J W; Meijer, E W; Paulus, W; Duncan, R

    2000-03-01

    Dendrimers are highly branched macromolecules of low polydispersity that provide many exciting opportunities for design of novel drug-carriers, gene delivery systems and imaging agents. They hold promise in tissue targeting applications, controlled drug release and moreover, their interesting nanoscopic architecture might allow easier passage across biological barriers by transcytosis. However, from the vast array of structures currently emerging from synthetic chemistry it is essential to design molecules that have real potential for in vivo biological use. Here, polyamidoamine (PAMAM, Starburst), poly(propyleneimine) with either diaminobutane or diaminoethane as core, and poly(ethylene oxide) (PEO) grafted carbosilane (CSi-PEO) dendrimers were used to study systematically the effect of dendrimer generation and surface functionality on biological properties in vitro. Generally, dendrimers bearing -NH(2) termini displayed concentration- and in the case of PAMAM dendrimers generation-dependent haemolysis, and changes in red cell morphology were observed after 1 h even at low concentrations (10 microg/ml). At concentrations below 1 mg/ml CSi-PEO dendrimers and those dendrimers with carboxylate (COONa) terminal groups were neither haemolytic nor cytotoxic towards a panel of cell lines in vitro. In general, cationic dendrimers were cytotoxic (72 h incubation), displaying IC(50) values=50-300 microg/ml dependent on dendrimer-type, cell-type and generation. Preliminary studies with polyether dendrimers prepared by the convergent route showed that dendrimers with carboxylate and malonate surfaces were not haemolytic at 1 h, but after 24 h, unlike anionic PAMAM dendrimers they were lytic. Cationic 125I-labelled PAMAM dendrimers (gen 3 and 4) administered intravenously (i.v.) to Wistar rats ( approximately 10 microg/ml) were cleared rapidly from the circulation (<2% recovered dose in blood at 1 h). Anionic PAMAM dendrimers (gen 2.5, 3.5 and 5.5) showed longer circulation

  9. Mobile OS Comparative Study

    OpenAIRE

    Joseph, Jyothy; K, Shinto Kurian

    2013-01-01

    In the fast growing mobile revolutionary era, many operating systems are playing vital role in present market. This study is intending to identify the apt and secure mobile based on mobile operating systems capability and user requirements.

  10. Comparative Packaging Study

    Science.gov (United States)

    Perchonok, Michele H.; Oziomek, Thomas V.

    2009-01-01

    Future long duration manned space flights beyond low earth orbit will require the food system to remain safe, acceptable and nutritious. Development of high barrier food packaging will enable this requirement by preventing the ingress and egress of gases and moisture. New high barrier food packaging materials have been identified through a trade study. Practical application of this packaging material within a shelf life test will allow for better determination of whether this material will allow the food system to meet given requirements after the package has undergone processing. The reason to conduct shelf life testing, using a variety of packaging materials, stems from the need to preserve food used for mission durations of several years. Chemical reactions that take place during longer durations may decrease food quality to a point where crew physical or psychological well-being is compromised. This can result in a reduction or loss of mission success. The rate of chemical reactions, including oxidative rancidity and staling, can be controlled by limiting the reactants, reducing the amount of energy available to drive the reaction, and minimizing the amount of water available. Water not only acts as a media for microbial growth, but also as a reactant and means by which two reactants may come into contact with each other. The objective of this study is to evaluate three packaging materials for potential use in long duration space exploration missions.

  11. Biodistribution imaging of a paclitaxel-hyaluronan bioconjugate

    Energy Technology Data Exchange (ETDEWEB)

    Banzato, Alessandra; Rondina, Maria [Department of Oncology and Surgical Sciences, University of Padua, I-35128 Padova (Italy); Melendez-Alafort, Laura; Zangoni, Elena; Nadali, Anna [Department of Pharmaceutical Sciences, University of Padua, Padova (Italy); Renier, Davide [Fidia Farmaceutici, Abano Terme (Italy); Moschini, Giuliano [Department of Physics, University of Padua, Padova (Italy); Mazzi, Ulderico [Department of Pharmaceutical Sciences, University of Padua, Padova (Italy); Zanovello, Paola [Department of Oncology and Surgical Sciences, University of Padua, I-35128 Padova (Italy); Istituto Oncologico Veneto, IOV-IRCCS, Padova (Italy); Rosato, Antonio [Department of Oncology and Surgical Sciences, University of Padua, I-35128 Padova (Italy); Istituto Oncologico Veneto, IOV-IRCCS, Padova (Italy)], E-mail: antonio.rosato@unipd.it

    2009-07-15

    Introduction: Gamma-ray detectors represent sensitive and noninvasive instruments to evaluate in vivo the metabolic trapping of radiopharmaceuticals. This study aimed to assess the imaging biodistribution of a [{sup 99m}Tc]-radiolabelled new prototype bioconjugate composed of paclitaxel linked to hyaluronan (ONCOFID-P). Methods: A small gamma camera providing high-resolution images was employed. Imaging of biodistribution following intravenous, intraperitoneal, intravesical and oral administration was carried out for a 2-h period in anesthetized mice receiving [{sup 99m}Tc]ONCOFID-P. At the end of the observation time, radioactivity in organs was directly measured. As a control, groups of mice were treated with free [{sup 3}H]paclitaxel given according to the same administration routes, and organ biodistribution of the drug was assessed after 2 h. Results: Intravenous inoculation of [{sup 99m}Tc]ONCOFID-P was followed by a rapid and strong liver uptake. In fact, almost 80% of the imaging signal was detected in this organ 10 min after injection and such value remained constant thereafter, thus indicating that the bioconjugate given through the intravenous route could be well suited to targeting primary or metastatic liver neoplasias. Imaging of the bladder, abdomen and gastrointestinal tract after local administration disclosed that the radiolabelled compound remained confined to the cavities, suggesting a potential regional application for transitional bladder cell carcinomas, ovarian cancers and gastric tumors, respectively. Free [{sup 3}H]paclitaxel biodistribution profoundly differed from that of [{sup 99m}Tc]ONCOFID-P. Conclusions: Conjugation of drugs with polymers results in new chemical entities characterized by a modified biodistribution pattern. Therefore, preclinical studies based on imaging analysis of such new compounds can suggest novel therapeutic applications.

  12. Persistent Luminescence Nanophosphor Involved Near-Infrared Optical Bioimaging for Investigation of Foodborne Probiotics Biodistribution in Vivo: A Proof-of-Concept Study.

    Science.gov (United States)

    Liu, Yaoyao; Liu, Jing-Min; Zhang, Dongdong; Ge, Kun; Wang, Peihua; Liu, Huilin; Fang, Guozhen; Wang, Shuo

    2017-09-20

    Probiotics has attracted great attention in food nutrition and safety research field, but thus far there are limited analytical techniques for visualized and real-time monitoring of the probiotics when they are ingested in vivo. Herein, the optical bioimaging technique has been introduced for investigation of foodborne probiotics biodistribution in vivo, employing the near-infrared (NIR) emitting persistent luminescence nanophosphors (PLNPs) of Cr 3+ -doped zinc gallogermanate (ZGGO) as the contrast nanoprobes. The ultrabrightness, super long afterglow, polydispersed size, low toxicity, and excellent photostability and biocompatibility of PLNPs were demonstrated to be qualified as a tracer for labeling probiotics via antibody (anti-Gram positive bacteria LTA antibody) recognition as well as contrast agent for long-term bioimaging the probiotics. In vivo optical bioimaging assay showed that the LTA antibody functionalized ZGGO nanoprobes that could be efficiently tagged to the probiobics were successfully applied for real-time monitoring and nondamaged probing of the biodistribution of probiotics inside the living body after oral administration. This work presents a proof-of-concept that exploited the bioimaging methodology for real-time and nondamaged researching the foodborne probiotics behaviors in vivo, which would open up a novel way of food safety detection and nutrition investigation.

  13. Biodistribution of N-isopropyl-p-iodoamphetamine

    International Nuclear Information System (INIS)

    Hoshi, Hiroaki; Jinnouchi, Seishi; Watanabe, Katsushi; Ueda, Takashi; Yamaguchi, Tadatoshi

    1987-01-01

    Biodistribution of N-isopropyl-p-iodoamphetamine (IMP) was experimentally studied for evaluating the usefullness of this radiopharmaceuticals for cerebral perfusion scintigraphy. IMP labeled with radioactive iodine (I-125, I-131), was injected intravenously in awake animals. The activity in the brain of male ddY mice injected 3.7 kBq (0.1 μCi) of I-125 IMP reached 8.0 (%Dose/g) at 10 min. after injection and it was almost constant till 120 min. Activity in the lung and heart was the highest just after injection, and rapidly decreased in the constant level lasting 30 min. to 120 min. Activity in the liver increased slowly and reached peak level at 60 min. Autoradiograms of male ddY mice injected 1.85 MBq (50 μCi) of I-131 IMP showed almost same activity in the spinal cord as the brain. Activities of I-131 IMP in normal brain of Sprague-Dawley rats injected 7.4 MBq (200 μCi) of I-131 IMP were 2.68 - 3.2 (%Dose/g) in the cerebral cortex and 0.59 - 0.66 (%Dose/g) in the white matter at 1 min. after injection. Activities in the cerebral cortex were slightly increased at 60 min. after injection and the activities in the white matter increased markedly at 60 min. and 6 hrs. after injection. The cerebral cortex to white matter ratios were about 5 at 1 min. or 10 min. and about 1 at 60 min. or 6 hrs. after injection. Autoradiograms of normal and ischemic rat brain showed local cerebral blood flow image, but the contrast between the gray matter and the white matter decreased at 60 min. or 6 hrs. Our study on the biodistribution of IMP showed the usefullness of this agent in cerebral perfusion imaging, and may be informative for the interpretation of images. (author)

  14. A Biodistribution and Toxicity Study of Cobalt Dichloride-N-Acetyl Cysteine in an Implantable MRI Marker for Prostate Cancer Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Frank, Steven J., E-mail: sjfrank@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Texas (United States); Johansen, Mary J. [Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Texas (United States); Martirosyan, Karen S. [Department of Physics and Astronomy, The University of Texas at Brownsville, Texas (United States); Gagea, Mihai; Van Pelt, Carolyn S.; Borne, Agatha [Department of Veterinary Medicine, Surgery, and Pathology, The University of Texas MD Anderson Cancer Center, Texas (United States); Carmazzi, Yudith; Madden, Timothy [Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Texas (United States)

    2013-03-15

    Purpose: C4, a cobalt dichloride-N-acetyl cysteine complex, is being developed as a positive-signal magnetic resonance imaging (MRI) marker to localize implanted radioactive seeds in prostate brachytherapy. We evaluated the toxicity and biodistribution of C4 in rats with the goal of simulating the systemic effects of potential leakage from C4 MRI markers within the prostate. Methods and Materials: 9-μL doses (equivalent to leakage from 120 markers in a human) of control solution (0.9% sodium chloride), 1% (proposed for clinical use), and 10% C4 solution were injected into the prostates of male Sprague-Dawley rats via laparotomy. Organ toxicity and cobalt disposition in plasma, tissues, feces, and urine were evaluated. Results: No C4-related morbidity or mortality was observed in the biodistribution arm (60 rats). Biodistribution was measurable after 10% C4 injection: cobalt was cleared rapidly from periprostatic tissue; mean concentrations in prostate were 163 μg/g and 268 μg/g at 5 and 30 minutes but were undetectable by 60 minutes. Expected dual renal-hepatic elimination was observed, with percentages of injected dose recovered in tissues of 39.0 ± 5.6% (liver), >11.8 ± 6.5% (prostate), and >5.3 ± 0.9% (kidney), with low plasma concentrations detected up to 1 hour (1.40 μg/mL at 5-60 minutes). Excretion in urine was 13.1 ± 4.6%, with 3.1 ± 0.54% recovered in feces by 24 hours. In the toxicity arm, 3 animals died in the control group and 1 each in the 1% and 10% groups from surgical or anesthesia-related complications; all others survived to scheduled termination at 14 days. No C4-related adverse clinical signs or organ toxicity were observed. Conclusion: C4-related toxicity was not observed at exposures at least 10-fold the exposure proposed for use in humans. These data demonstrating lack of systemic toxicity with dual routes of elimination in the event of in situ rupture suggest that C4 warrants further investigation as an MRI marker for prostate

  15. Biodistribution of 99mTc labelled anti TAG 72 chimeric McAb ccM4 in nude mice and preliminary clinical study

    International Nuclear Information System (INIS)

    Ma Qingjie; Zhao Jie; Zhang Yingnan; Gao Fengtong; Liu Shuqing

    1995-01-01

    Chimeric McAb ccM 4 was labelled with 99m Tc by direct method. The antibody was reduced by molar excess 2-mercaptoethanol (2-ME; Ab, 1000:1). The reduced ccM 4 chimeric McAb was mixed with 99m Tc reduced by SnCl 2 and 99m Tc labelling efficiency was 98%. The immunoreactivity did not change after labelling. The biodistribution of 99m Tc-ccM 4 was performed in nude mice and patients with stomach carcinoma. There was significantly more radioactivity in tumor than in the rest of the body in nude mice. Radioimmunoimaging of ccM 4 in 10 patients of gastric cancer was also presented

  16. Predicting the biodistribution of radiolabeled cMORF effector in MORF-pretargeted mice

    International Nuclear Information System (INIS)

    Liu, Guozheng; Dou, Shuping; He, Jiang; Liu, Xinrong; Rusckowski, Mary; Hnatowich, Donald J.

    2007-01-01

    Pretargeting with phosphorodiamidate morpholino oligomers (MORFs) involves administration of a MORF-conjugated anti-tumor antibody such as MN14 as a pretargeting agent before that of the radiolabeled complementary MORF (cMORF) as the effector. The dosages of the pretargeting agent and effector, the pretargeting interval, and the detection time are the four pretargeting variables. The goal of this study was to develop a semiempirical description capable of predicting the biodistribution of the radiolabeled effector in pretargeted mice and then to compare predictions with experimental results from pretargeting studies in tumored animals in which the pretargeting interval and the detection time were both fixed but the dosages of both the effector and the pretargeting agent were separately varied. Pretargeting studies in LS174T tumored mice were performed using the anti-CEA antibody MN14 conjugated with MORF and the cMORF radiolabeled with 99m Tc. A description was developed based on our previous observations in the same mouse model of the blood and tumor levels of MORF-MN14, accessibility of MORF-MN14 to labeled cMORF, the tumor accumulation of labeled cMORF relative to MORF-MN14 levels therein, and the kidney accumulation of labeled cMORF. The predicted values were then compared with the experimental values. The predicted biodistribution of the radiolabeled effector and the experimental data were in gratifying agreement in normal organs, suggesting that the description of the pretargeting process was reliable. The tumor accumulations occasionally fell outside two standard deviations of that predicted, but after tumor size correction, good agreement between predicted and experimental values was observed here as well. A semiempirical description of the biodistribution of labeled cMORF was capable of predicting the biodistribution of the radiolabeled effector in the pretargeted tumored mouse model, demonstrating that the underlying pretargeting concepts are correct. We

  17. Anti-CEA aptamers labeled with {sup 99m}Tc: encapsulation studies in long-circulating and pH-sensitive liposomes, biodistribution and imaging

    Energy Technology Data Exchange (ETDEWEB)

    Leonel, M.F.V.; Andrade, A.S.R. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Oliveira, M.C.; Cardoso, V.N.; Barros, A.L.B. [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Faculdade de Farmacia

    2015-07-01

    Colorectal cancer (CRC) is one of the leading cancers and the carcinoembryonic antigen (CEA) is a tumor marker widely used in diagnosis since it is overexpressed in tumor cells. Acid nucleic aptamers with high affinity and specificity for this antigen become promising molecules for CRC diagnosis by imaging. However, due to the action of nucleases in vivo, they have been investigated for association with liposomes, such as long-circulating and pH-sensitive liposomes (SPHL) that can be destabilized in the tumor region releasing aptamers and contributing to the CRC diagnosis by scintigraphy. In this work, SpHL containing DOPE, CHEMS and mPEG{sub 2000}-DSPE were characterized by analyzing mean diameter, polydispersity index and zeta potential. The anti-CEA aptamers Apt3 and Apt3-Amino were labeled with technetium-99m and the encapsulation efficiency (EE) of {sup 99m}Tc-Apt3 in the SpHL by dehydration-rehydration (modified DRV) and freeze-thaw (FT) were analyzed, both in the presence of cryoprotectants. Biodistribution and scintigraphic images were performed at 1h and 4h post-injection of {sup 99m}Tc-Apt3-amino, {sup 99m}Tc-Apt3-SpHL or {sup 99m}Tc-Apt3-amino-SpHL complexes in Balb/c healthy mice. The SpHL dispersions were homogeneous. The radiolabeling yield with technetium-99m was over 90% for all complexes. By the dehydration-rehydration method, the SpHL increased over 200% after encapsulation procedure. By the freeze-thaw method, the SpHL size increased only 13.7%. Free {sup 99m}Tc-Apt3-amino showed to be cleared by renal via with high levels of radioactivity in the kidney and bladder, however, the {sup 99m}Tc-Apt3-SpHL and {sup 99m}Tc-Apt3-amino-SpHL clearly indicated high uptake by liver and spleen. The biodistribution of {sup 99m}Tc-Apt3-SpHL showed significant uptake of radioactivity by stomach and thyroid indicating less stability of the Apt3 radiolabelling in relation to Apt3-amino. (author)

  18. Anti-CEA aptamers labeled with 99mTc: encapsulation studies in long-circulating and pH-sensitive liposomes, biodistribution and imaging

    International Nuclear Information System (INIS)

    Leonel, M.F.V.; Andrade, A.S.R.; Oliveira, M.C.; Cardoso, V.N.; Barros, A.L.B.

    2015-01-01

    Colorectal cancer (CRC) is one of the leading cancers and the carcinoembryonic antigen (CEA) is a tumor marker widely used in diagnosis since it is overexpressed in tumor cells. Acid nucleic aptamers with high affinity and specificity for this antigen become promising molecules for CRC diagnosis by imaging. However, due to the action of nucleases in vivo, they have been investigated for association with liposomes, such as long-circulating and pH-sensitive liposomes (SPHL) that can be destabilized in the tumor region releasing aptamers and contributing to the CRC diagnosis by scintigraphy. In this work, SpHL containing DOPE, CHEMS and mPEG 2000 -DSPE were characterized by analyzing mean diameter, polydispersity index and zeta potential. The anti-CEA aptamers Apt3 and Apt3-Amino were labeled with technetium-99m and the encapsulation efficiency (EE) of 99m Tc-Apt3 in the SpHL by dehydration-rehydration (modified DRV) and freeze-thaw (FT) were analyzed, both in the presence of cryoprotectants. Biodistribution and scintigraphic images were performed at 1h and 4h post-injection of 99m Tc-Apt3-amino, 99m Tc-Apt3-SpHL or 99m Tc-Apt3-amino-SpHL complexes in Balb/c healthy mice. The SpHL dispersions were homogeneous. The radiolabeling yield with technetium-99m was over 90% for all complexes. By the dehydration-rehydration method, the SpHL increased over 200% after encapsulation procedure. By the freeze-thaw method, the SpHL size increased only 13.7%. Free 99m Tc-Apt3-amino showed to be cleared by renal via with high levels of radioactivity in the kidney and bladder, however, the 99m Tc-Apt3-SpHL and 99m Tc-Apt3-amino-SpHL clearly indicated high uptake by liver and spleen. The biodistribution of 99m Tc-Apt3-SpHL showed significant uptake of radioactivity by stomach and thyroid indicating less stability of the Apt3 radiolabelling in relation to Apt3-amino. (author)

  19. Biodistribution of gyroxin using 125I as radiotracer

    International Nuclear Information System (INIS)

    Alves da Silva, J.A.; Ribela, M.T.C.P.; Rogero, J.R.; Camillo, M.A.P.; Muramoto, E.

    2006-01-01

    The use of radiotracers in the research of animal venom has been scarce, although it allows an excellent approach to follow the process of bioavailability, biodistribution and kinetics of toxins. The purpose of this study was to assess gyroxin action mechanism, transport, compartments and action sites. This toxin is a thrombin-like and causes the barrel rotation syndrome. The gyroxin was labeled with 125 I and used as a tracer for the in vivo assay in mice. Blood samples and organs were collected at different time intervals, weighed and analyzed in a gamma-counter. The data was related with tissues distribution of protease activated receptor (PAR). Biodistribution assay allowed dividing the organs into three groups. The first one with the organs that followed the blood kinetics, the second with the organs related to metabolisms and elimination, and the third with the organs in which the gyroxin concentration increased during the observation period. (author)

  20. Study of biodistribution of lipidic nanospheres charged with cis-diaminedichloroplatinum (II) and labelled with radioactive nuclei of Indium-111; Estudio de biodistribucion de nanoesferas lipidicas cargadas con cis-diaminodicloroplatino (II) y marcadas con nucleos radioactivos de Indio-111

    Energy Technology Data Exchange (ETDEWEB)

    Lopez R, V.; Juarez O, C.; Medina L, A. [Unidad de Investigacion Biomedica en Cancer INCAN-UNAM, Mexico D.F. (Mexico); Perez C, E.; Garcia L, P. [Instituto nacional de cancerologia, Mexico D.F. (Mexico)

    2007-07-01

    The general objective of the study was to evaluate the lipidic nanospheres biodistribution charged with cis-diaminedichloroplatinum (II) (cis-DDP) and labelled with radioactive nuclei of Indium-111 (Lip-Cis-in-111) in Wistar rats and in a tumoral model of CaCu. The conclusions were: 1. The system Lip-Cis-in-111 it presents a very fast elimination probably, to a fast recognition response of the reticuloendothelial system (RES). 2. It is planned to make modifications to the formulation to increase the quantity of the hydrophilic polymer (PEG), so that its time of residence in the blood is bigger and allow a bigger accumulation in the tumor. (Author)

  1. Preclinical pharmacokinetics, biodistribution, radiation dosimetry and acute toxicity studies required for regulatory approval of a Clinical Trial Application for a Phase I/II clinical trial of 111In-BzDTPA-pertuzumab

    International Nuclear Information System (INIS)

    Lam, Karen; Chan, Conrad; Done, Susan J.; Levine, Mark N.; Reilly, Raymond M.

    2015-01-01

    Introduction: 111 In-BzDTPA-pertuzumab is a novel imaging probe for detecting changes in HER2 expression in breast cancer (BC) caused by treatment with trastuzumab (Herceptin). Our aim was to evaluate the pharmacokinetics, normal tissue biodistribution, radiation dosimetry and acute toxicity of 111 In-BzDTPA-pertuzumab in non-tumor bearing mice in order to obtain regulatory approval to advance this agent to a first-in-humans Phase I/II clinical trial. Methods: Biodistribution and pharmacokinetic studies were performed in non-tumor bearing Balb/c mice injected i.v. with 111 In-BzDTPA-pertuzumab (2.5 MBq; 2 μg). The cumulative number of disintegrations per source organ derived from the biodistribution data was used to predict the radiation absorbed doses in humans using OLINDA/EXM software. Acute toxicity was studied at two weeks post-injection of 111 In-BzDTPA-pertuzumab (1.0 MBq, 20 μg) with comparison to control mice injected with unlabeled BzDTPA-pertuzumab (20 μg) or Sodium Chloride Injection USP. The dose of 111 In-BzDTPA-pertuzumab corresponded to 23-times the human radioactivity dose and 10-times the protein dose on a MBq/kg and mg/kg basis, respectively. Toxicity was assessed by monitoring body mass, complete blood cell count (CBC), hematocrit (Hct), hemoglobin (Hb), serum creatinine (SCr) and alanine aminotransferease (ALT) and by histopathological examination of tissues at necropsy. Results: 111 In-BzDTPA-pertuzumab exhibited a biphasic elimination from the blood with a distribution half-life (t 1/2 α) of 3.8 h and an elimination half-life (t 1/2 β) of 228.2 h. The radiopharmaceutical was distributed mainly in the blood, heart, lungs, liver, kidneys and spleen. The projected whole-body radiation absorbed dose in humans was 0.05 mSv/MBq corresponding to a total of 16.8 mSv for three separate administrations of 111 In-BzDTPA-pertuzumab (111 MBq) planned for the Phase I/II trial. There were slight changes in Hb and SCr levels associated with

  2. Biodistribution of 99m technetium labeled creatinine in healthy rats

    International Nuclear Information System (INIS)

    Yilmaz, O.; Soylu, A.; Kavukcu, S.; Lambrecht, F. Yurt; Durkan, K.

    2007-01-01

    The distribution of creatinine, one of the toxic guanidine compounds, in various tissues has not been studied in detail by using radiolabeled creatinine. Our objective was to investigate the biodistribution of creatinine labeled with 99m technetium ( 99m Tc) by the stannous (II) chloride method in healthy male Wistar rats. Quality controls were carried out by radio thin layer chromatography, high-performance liquid chromatography, and paper electrophoresis. The labeling yield was 85 ± 2% under optimum conditions (pH 7 and 100 μg stannous chloride). Rats (N 12) were injected intravenously with 99m Tc creatinine and their blood and visceral organs were evaluated for 99m Tc-creatinine uptake as percent of the injected dose per gram wet weight of each tissue (%ID/g). The lowest amount of uptake was detected in the brain and testis. When the rate of uptake was evaluated, only the kidney showed increasing rates of uptake of 99m Tc-creatinine throughout the study. Kidneys showed the highest amount of uptake throughout the study (P < 0.001 compared to all other organs), followed by liver, spleen and lung tissue. (author)

  3. Biodistribution of technetium-{sup 99m} pertechnetate after Roux-en-Y gastric bypass (Capella technique) in rats

    Energy Technology Data Exchange (ETDEWEB)

    Rego, Amalia Cinthia Meneses do; Jacome, Daniel Torres; Ramalho, Rachel de Alcantara Oliveira [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil); Araujo-Filho, Irami; Azevedo, Italo Medeiros; Medeiros, Aldo Cunha, E-mail: aldo@ufrnet.b [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Dept. of Surgery

    2010-01-15

    Purpose: The biodistribution of sodium pertechnetate, the most used radiopharmaceutical in nuclear medicine, has not been studied in details after bariatric surgery. The objective was to investigate the effect of Roux-en-Y gastric bypass (RYGB) on biodistribution of sodium pertechnetate (Na{sup 99m}Tc-) in organs and tissues of rats. Methods: Twelve rats were randomly divided into two groups of 6 animals each. The RYGB group rats were submitted to the Roux-en-Y gastric bypass and the control group rats were not operated. After 15 days, all rats were injected with 0.1mL of Na{sup 99m}Tc- via orbital plexus with average radioactivity of 0.66 MBq. After 30 minutes, liver, stomach, thyroid, heart, lung, kidney and femur samples were harvested, weighed and percentage of radioactivity per gram (%ATI/g) of each organ was determined by gamma counter Wizard Perkin-Elmer. We applied the Student t test for statistical analysis, considering p<0.05 as significant. Results: Significant reduction in mean %ATI/g was observed in the liver, stomach and femur in the RYGB group animals, compared with the control group rats (p<0.05). In other organs no significant difference in %ATI/g was observed between the two groups. Conclusion: This work contributes to the knowledge that the bariatric surgery RYGB modifies the pattern of biodistribution of Na{sup 99m}Tc{sup -}. (author)

  4. Dual-modality NIRF-MRI cubosomes and hexosomes: High throughput formulation and in vivo biodistribution

    Energy Technology Data Exchange (ETDEWEB)

    Tran, Nhiem, E-mail: nhiem.tran@rmit.edu.au [CSIRO Manufacturing, Clayton, Victoria 3168 (Australia); Australian Synchrotron, Clayton, Victoria 3168 (Australia); RMIT University, Melbourne, Victoria 3000 (Australia); Bye, Nicole; Moffat, Bradford A. [Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, Victoria 3010 (Australia); Wright, David K. [Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, Victoria 3010 (Australia); The Florey Institute of Neuroscience and Mental Health, Parkville, Victoria 3052 (Australia); Cuddihy, Andrew [Myeloma Research Group, Australian Centre for Blood Diseases, Monash Central Clinical School, The Alfred Hospital, Melbourne, Victoria 3004 (Australia); Hinton, Tracey M. [CSIRO Australian Animal Health Laboratory, East Geelong, Victoria 3219 (Australia); Hawley, Adrian M. [Australian Synchrotron, Clayton, Victoria 3168 (Australia); Reynolds, Nicholas P. [CSIRO Manufacturing, Clayton, Victoria 3168 (Australia); ARC Training Centre for Biodevices, Faculty of Science Engineering and Technology, Swinburne University of Technology, Melbourne, Victoria 3122 (Australia); Waddington, Lynne J.; Mulet, Xavier [CSIRO Manufacturing, Clayton, Victoria 3168 (Australia); Turnley, Ann M. [Department of Anatomy and Neuroscience, The University of Melbourne, Parkville, Victoria 3010 (Australia); Morganti-Kossmann, M. Cristina [Australian New Zealand Intensive Care Research Centre, Monash University, Victoria 3800 (Australia); Department of Child Health, Barrow Neurological Institute, University of Arizona, Phoenix, AZ 85004 (United States); Muir, Benjamin W., E-mail: ben.muir@csiro.au [CSIRO Manufacturing, Clayton, Victoria 3168 (Australia)

    2017-02-01

    Engineered nanoparticles with multiple complementary imaging modalities are of great benefit to the rapid treatment and diagnosis of disease in various organs. Herein, we report the formulation of cubosomes and hexosomes that carry multiple amphiphilic imaging contrast agents in their self-assembled lipid bilayers. This is the first report of the use of both near infrared fluorescent (NIRF) imaging and gadolinium lipid based magnetic resonance (MR) imaging modalities in cubosomes and hexosomes. High-throughput screening was used to rapidly optimize formulations with desirable nano-architectures and low in vitro cytotoxicity. The dual-modal imaging nanoparticles in vivo biodistribution and organ specific contrast enhancement were then studied. The NIRF in vivo imaging results indicated accumulation of both cubosomes and hexosomes in the liver and spleen of mice up to 20 h post-injection. Remarkably, the biodistribution of the nanoparticle formulations was affected by the mesophase (i.e. cubic or hexagonal), a finding of significant importance for the future use of these compounds, with hexosomes showing higher accumulation in the spleen than the liver compared to cubosomes. Furthermore, in vivo MRI data of animals injected with either type of lyotropic liquid crystal nanoparticle displayed enhanced contrast in the liver and spleen. - Highlights: • Dual modality NIRF-MR imaging self-assembled lipid nanoparticles were formulated. • The nanoparticles showed cubic and hexagonal internal nanostructures. • Biodistribution experiments revealed accumulation of both cubosomes and hexosomes in spleen and liver of mice. • Pre-clinical MRI displayed enhanced contrast in spleen and liver of mice that received either cubosomes or hexosomes.

  5. Docetaxel-loaded PLGA and PLGA-PEG nanoparticles for intravenous application: pharmacokinetics and biodistribution profile.

    Science.gov (United States)

    Rafiei, Pedram; Haddadi, Azita

    2017-01-01

    Docetaxel is a highly potent anticancer agent being used in a wide spectrum of cancer types. There are important matters of concern regarding the drug's pharmacokinetics related to the conventional formulation. Poly(lactide- co -glycolide) (PLGA) is a biocompatible/biodegradable polymer with variable physicochemical characteristics, and its application in human has been approved by the United States Food and Drug Administration. PLGA gives polymeric nanoparticles with unique drug delivery characteristics. The application of PLGA nanoparticles (NPs) as intravenous (IV) sustained-release delivery vehicles for docetaxel can favorably modify pharmacokinetics, biofate, and pharmacotherapy of the drug in cancer patients. Surface modification of PLGA NPs with poly(ethylene glycol) (PEG) can further enhance NPs' long-circulating properties. Herein, an optimized fabrication approach has been used for the preparation of PLGA and PLGA-PEG NPs loaded with docetaxel for IV application. Both types of NP formulations demonstrated in vitro characteristics that were considered suitable for IV administration (with long-circulating sustained-release purposes). NP formulations were IV administered to an animal model, and docetaxel's pharmacokinetic and biodistribution profiles were determined and compared between study groups. PLGA and PEGylated PLGA NPs were able to modify the pharmacokinetics and biodistribution of docetaxel. Accordingly, the mode of changes made to pharmacokinetics and biodistribution of docetaxel is attributed to the size and surface properties of NPs. NPs contributed to increased blood residence time of docetaxel fulfilling their role as long-circulating sustained-release drug delivery systems. Surface modification of NPs contributed to more pronounced docetaxel blood concentration, which confirms the role of PEG in conferring long-circulation properties to NPs.

  6. Dual-modality NIRF-MRI cubosomes and hexosomes: High throughput formulation and in vivo biodistribution

    International Nuclear Information System (INIS)

    Tran, Nhiem; Bye, Nicole; Moffat, Bradford A.; Wright, David K.; Cuddihy, Andrew; Hinton, Tracey M.; Hawley, Adrian M.; Reynolds, Nicholas P.; Waddington, Lynne J.; Mulet, Xavier; Turnley, Ann M.; Morganti-Kossmann, M. Cristina; Muir, Benjamin W.

    2017-01-01

    Engineered nanoparticles with multiple complementary imaging modalities are of great benefit to the rapid treatment and diagnosis of disease in various organs. Herein, we report the formulation of cubosomes and hexosomes that carry multiple amphiphilic imaging contrast agents in their self-assembled lipid bilayers. This is the first report of the use of both near infrared fluorescent (NIRF) imaging and gadolinium lipid based magnetic resonance (MR) imaging modalities in cubosomes and hexosomes. High-throughput screening was used to rapidly optimize formulations with desirable nano-architectures and low in vitro cytotoxicity. The dual-modal imaging nanoparticles in vivo biodistribution and organ specific contrast enhancement were then studied. The NIRF in vivo imaging results indicated accumulation of both cubosomes and hexosomes in the liver and spleen of mice up to 20 h post-injection. Remarkably, the biodistribution of the nanoparticle formulations was affected by the mesophase (i.e. cubic or hexagonal), a finding of significant importance for the future use of these compounds, with hexosomes showing higher accumulation in the spleen than the liver compared to cubosomes. Furthermore, in vivo MRI data of animals injected with either type of lyotropic liquid crystal nanoparticle displayed enhanced contrast in the liver and spleen. - Highlights: • Dual modality NIRF-MR imaging self-assembled lipid nanoparticles were formulated. • The nanoparticles showed cubic and hexagonal internal nanostructures. • Biodistribution experiments revealed accumulation of both cubosomes and hexosomes in spleen and liver of mice. • Pre-clinical MRI displayed enhanced contrast in spleen and liver of mice that received either cubosomes or hexosomes.

  7. Tc 99m - scorpion venom: labelling, biodistribution and scintiimaging

    International Nuclear Information System (INIS)

    Murugesan, S.; Noronha, O.P.D.; Samuel, A.M.; Murthy, K. Radha Krishna

    1999-01-01

    Labelling of scorpion (Mesobuthus tamulus concanesis Pocock) venom was successfully achieved with Tc 99m using direct tin reduction procedure. Biodistribution studies were carried out in Wistar rats at different time intervals after i.v. administration of the labelled venom. Scintiimages were obtained after scorpion envenoming using a large field of view gamma camera to ascertain the pharmacological action of venom in the body. Within 5 min of administration, labelled venom was found in the blood (27.7%), muscle (30.11%), bone (13.3%), kidneys (11.5%), liver (10.4%) and other organs. The level of venom in the kidneys was higher than in the liver. The labelled venom was excreted through renal and hepatobiliary pathways. An immunoreactivity study was carried out in rabbits after i.v. injection of labelled scorpion venom followed by the injection of the species specific antivenom. A threefold increase in uptake by the kidneys ss was observed compared with that seen with scorpion venom alone. the neutralisation of the venom in the kidneys was higher than in the liver. (author)

  8. Effects of Glycosylation on Biodistribution and Imaging Quality of Necrotic Myocardium of Iodine-131-Labeled Sennidins.

    Science.gov (United States)

    Li, Ling; Zhang, Dongjian; Yang, Shengwei; Song, Shaoli; Li, Jindian; Wang, Qin; Wang, Cong; Feng, Yuanbo; Ni, Yicheng; Zhang, Jian; Liu, Wei; Yin, Zhiqi

    2016-12-01

    Sennidins are necrosis-avid agents for noninvasive assessment of myocardial viability which is important for patients with myocardial infarction (MI). However, high accumulation of radioactivity in the liver interferes with the assessment of myocardial viability. In this study, we compared sennidins with sennosides to investigate the effects of glycosylation on biodistribution and imaging quality of sennidins. Sennidin A (SA), sennidin B (SB), sennoside A (SSA), and sennoside B (SSB) were labeled with I-131. In vitro binding to necrotic cells and hepatic cells and in vivo biodistribution in rats with muscular necrosis were evaluated by gamma counting, autoradiography, and histopathology. Single photon emission computed tomography/computed tomography (SPECT/CT) images were acquired in rats with acute MI. The uptake of [ 131 I]SA, [ 131 I]SSA, [ 131 I]SB, and [ 131 I]SSB in necrotic cells was significantly higher than that in viable cells (p sennosides than those with [ 131 I]sennidins (p < 0.01). Autoradiography showed preferential accumulation of these four radiotracers in necrotic areas of muscle, confirmed by histopathology. SPECT/CT imaging studies showed better image quality with [ 131 I]SSB than with [ 131 I]SB due to less liver interference. Glycosylation significantly decreased the liver uptake and improved the quality of cardiac imaging. [ 131 I]SSB may serve as a promising necrosis-avid agent for noninvasive assessment of myocardial viability.

  9. SU-F-J-100: Standardized Biodistribution Template for Nuclear Medicine Dosimetry Collection and Reporting

    Energy Technology Data Exchange (ETDEWEB)

    Kesner, A [University of Colorado, Anschutz Medical Campus, Aurora, Colorado (United States); Poli, G [International Atomic Energy Agency, Vienna, Vienna (Austria); Beykan, S; Lassman, M [University of Wuerzburg, Wuerzberg, Wuerzberg (Germany)

    2016-06-15

    Purpose: As the field of Nuclear Medicine moves forward with efforts to integrate radiation dosimetry into clinical practice we can identify the challenge posed by the lack of standardized dose calculation methods and protocols. All personalized internal dosimetry is derived by projecting biodistribution measurements into dosimetry calculations. In an effort to standardize organization of data and its reporting, we have developed, as a sequel to the EANM recommendation of “Good Dosimetry Reporting”, a freely available biodistribution template, which can be used to create a common point of reference for dosimetry data. It can be disseminated, interpreted, and used for method development widely across the field. Methods: A generalized biodistribution template was built in a comma delineated format (.csv) to be completed by users performing biodistribution measurements. The template is available for free download. The download site includes instructions and other usage details on the template. Results: This is a new resource developed for the community. It is our hope that users will consider integrating it into their dosimetry operations. Having biodistribution data available and easily accessible for all patients processed is a strategy for organizing large amounts of information. It may enable users to create their own databases that can be analyzed for multiple aspects of dosimetry operations. Furthermore, it enables population data to easily be reprocessed using different dosimetry methodologies. With respect to dosimetry-related research and publications, the biodistribution template can be included as supplementary material, and will allow others in the community to better compare calculations and results achieved. Conclusion: As dosimetry in nuclear medicine become more routinely applied in clinical applications, we, as a field, need to develop the infrastructure for handling large amounts of data. Our organ level biodistribution template can be used as a

  10. Noninvasive optical imaging of nanomedicine biodistribution

    Czech Academy of Sciences Publication Activity Database

    Kunjachan, S.; Gremse, F.; Theek, B.; Koczera, P.; Pola, Robert; Pechar, Michal; Etrych, Tomáš; Ulbrich, Karel; Storm, G.; Kiessling, F.; Lammers, T.

    2013-01-01

    Roč. 7, č. 1 (2013), s. 252-262 ISSN 1936-0851 R&D Projects: GA ČR GAP301/11/0325 Institutional research plan: CEZ:AV0Z40500505 Institutional support: RVO:61389013 Keywords : nanomedicine * drug targeting * biodistribution Subject RIV: CD - Macromolecular Chemistry Impact factor: 12.033, year: 2013

  11. Biodistribution of Carbon Nanotubes in Animal Models

    DEFF Research Database (Denmark)

    Jacobsen, Nicklas Raun; Møller, Peter Horn; Clausen, Per Axel

    2017-01-01

    The many interesting physical and chemical properties of carbon nanotubes (CNT) make it one of the most commercially attractive materials in the era of nanotechnology. Here, we review the recent publications on in vivo biodistribution of pristine and functionalized forms of single-walled and multi...

  12. Effect of tripanossomicide benznidazole (Rochagan) on the biodistribution of sodium pertechnetate (Na{sup 99m}TcO4) in Wistar rats

    Energy Technology Data Exchange (ETDEWEB)

    Barbosa, Vanessa Santos de Arruda; Holanda, Cecilia Maria de Carvalho Xavier; Silva, Roseane Pereira da; Medeiros, Aldo Cunha [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Centro de Ciencias da Saude]. E-mail: vambio@oi.com.br; Oliveira, Daniel Pereira de; Silva Junior, Mauricio Ferreira da; Oliveira, Elias Herculano de [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Centro de Biociencias. Dept. de Microbiologia e Parasitologia; Spyrides, Maria Helena Constantino [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Dept. de Estatistica

    2008-12-15

    Benznidazole, a drug with specific anti-Trypanosoma cruzi activity, is used in the treatment of Chagas' disease. The radiopharmaceutical sodium pertechnetate (Na{sup 99m}TcO{sub 4}) is used to obtain diagnostic images of the stomach, thyroid, parathyroids, salivary glands, brain and in the study of esophageal reflux and blood flow. This study aimed at evaluating in vivo the influence of benznidazole treatment on the sodium pertechnetate biodistribution in Wistar rats. The percentage of radioactivity per gram (%ATI/g) of various organs (brain, heart, esophagus, stomach, small intestine, large intestine, spleen, liver, muscle and blood) was determined. Comparing the treated rats with the controls, we observed that sodium pertechnetate biodistribution did not change when administered to rats treated for thirty days with benznidazole. (author)

  13. Radioiodine-labeling of tetrahydropalmatine and its biodistribution in mice

    International Nuclear Information System (INIS)

    Tan Cheng; Lin Xiufeng; Zhang Li; Chen Bo; Cao Guoxian; Yu Huixin; Song Cuicui

    2008-01-01

    The work was to investigate radioiodinated tetrahydropalmatine and its biodistribution in mice. Tetrahydropalmatine was labeled with 131 I using the chloramine-T method and the labeled compound were characterized by polyamide TLC. The animals were sacrificed at different times after radiopharmaceutical i.v. administration. The interested tissues samples were collected, and percent injected dose per gram (%ID·g -1 ) was calculated for each sample. The labeling yield of 131 I-tetrahydropalmatine was 76% and its RCPs were 97.3%, 95.4%, and 96.8% after 1, 7 and 20 days, respectively. Biodistribution in mice demonstrated that 131 I-tetrahydropalmatine was extensive, and it was metabolized mainly in liver and kidney, which contained of 14.35% and 6.55% ID·g -1 at 5 min, respectively, with 3.26% and 1.20% ID·g -1 at 4h, respectively. Comparatively high 131 I-tetrahydropalmatine was found in intestine and fat, but clearance was slow, 3.91% and 3.05% at 5 min and decreased to 0.79% and 0.37% at 4 h. The results also showed that 131 I-tetrahydropalmatine could well penetrate the blood-brain barrier to attain a maximal level in brain tissue within 5-10 min, but it mostly was cleaned out after 2 h. There was no significant difference in brain regions despite of highest biodistribution in parietal lobe. In conclusion, 131 I-tetrahydropalmatine was stable and it was metabolized mainly in liver and kidney, but there was no significant difference in brain regions. (authors)

  14. [Comparative studies of face recognition].

    Science.gov (United States)

    Kawai, Nobuyuki

    2012-07-01

    Every human being is proficient in face recognition. However, the reason for and the manner in which humans have attained such an ability remain unknown. These questions can be best answered-through comparative studies of face recognition in non-human animals. Studies in both primates and non-primates show that not only primates, but also non-primates possess the ability to extract information from their conspecifics and from human experimenters. Neural specialization for face recognition is shared with mammals in distant taxa, suggesting that face recognition evolved earlier than the emergence of mammals. A recent study indicated that a social insect, the golden paper wasp, can distinguish their conspecific faces, whereas a closely related species, which has a less complex social lifestyle with just one queen ruling a nest of underlings, did not show strong face recognition for their conspecifics. Social complexity and the need to differentiate between one another likely led humans to evolve their face recognition abilities.

  15. Labelling, biodistribution and compartmental analysis of N-acetylcysteine labelled with Tc-99m. Comparative investigation with with {sup 99m} Tc-MIBI in an in vivo tumoral model; Estudo de marcacao, biodistribuicao e analise compartimental da N-acetil cisteina marcada com Tc-99m. Investigacao comparativa com MIBI-{sup 99m}Tc em modelo tumoral in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Faintuch, Bluma Linkowski

    1997-07-01

    Labelling and biodistribution studies were done with two different ligands, respectively Methoxy isobutyl isonitrile (MIBI) and N-acetylcysteine (NAC), employing Tc-99m as a tracer. The main objective was to assess the pharmacokinetic properties of the second substance, aiming at its possible application in cancer diagnosis. To this purpose an in vivo investigation was done using healthy and tumor-bearing rats with experimental cancer. Images of tumor-bearing rats registered in a scintillation camera indicated that with {sup 99m} Tc-MIBI none of the two selected times was adequate for visualization of the cancer mass. In contrast, {sup 99m} Tc-NAC permitted clear identification of the humor, four hours after injection. The results have demonstrated that {sup 99m} Tc-NAC is a radiopharmaceutical with affinity for cancer tissue and promising for further investigation concerning imaging diagnosis of tumors. (author)

  16. Pharmacokinetics and biodistribution of radiolabeled avidin, streptavidin and biotin

    International Nuclear Information System (INIS)

    Rosebrough, S.F.

    1993-01-01

    The extraordinarily high affinity of avidin and streptavidin for biotin may be exploited in a two-step approach for delivering radiolabeled biotin derivatives suitable for imaging and therapy to target-bound streptavidin or avidin conjugated monoclonal antibodies (MAbs). The in vivo pharmacokinetics and biodistribution of radiolabeled avidin, streptavidin (SA) and DTPA-biocytinamide (DTPA-biotin) were studied in the rabbit and dog. SA circulated in the blood similar to other 60 kDa proteins, avidin cleared immediately and DTPA-biotin exhibited plasma clearance by glomerular filtration. (author)

  17. Radioiodine labeling of resveratrol and its biodistribution in mice

    International Nuclear Information System (INIS)

    Chen Bo; Yu Huixin; Tan Cheng; Lin Xiufeng; Zhang Li; Cao Guoxian; Luo Shineng

    2008-01-01

    In order to investigate the preparation of radioiodinated resveratrol and its biodistribution in mice, resveratrol was labeled with 131 I using lactoperoxidase methods and purified by ethyl acetate. The radiolabeled compound was characterized by polyamide TLC, in which the substratum of V trichoromethane : V acetone : V ethanol : V Adam's ale =4 : 4 : 0.5 : 0.4 was used as the developing agent. Biodistribution studies were accomplished on KM mice. At different time after radiopharmaceutical i.v. administration (0.185 MBq 131 I- tetrahydropalmatine/mouse), the animals were sacrificed (n=5 animals for each time). Blood and the interested tissues were collected, washed, weighted and counted. The percent injected dose per gram (%ID·g -1 ) was calculated for each sample. The labeling yield of 131 I-resveratrol is 69.3% and its RCPs are 95.9%, 92.0%, 90.4%, and 90.1% after 1, 3, 7 and 15 d, respectively. Biodistribution in mice demonstrates that 131 I-resveratrol is distributed into broad organs and tissues. However, it reveals higher levels in liver, kidney and intestine than in other tissues. In liver and kidney, the %ID· g -1 are 16.35% and 13.05% at 5 min, respectively. 131 I-resveratrol is metabolized mainly through liver and kidney. Simultaneously, its high distribution is also found in intestine. The %ID·g -1 of 131 I-resveratrol is 11.70% at 10 min; the activity in thyroid increases with time. Therefore, the 131 I-resveratrol is worthy of further investigation to trace the compound in vivo and ex vivo. (authors)

  18. Radioiodine-Labeling of Chlorpyrifos and Its Biodistribution in Mice

    Directory of Open Access Journals (Sweden)

    DIAO Yao

    2015-11-01

    Full Text Available To investigate the preparation of radioiodinated Chlorpyrifos and its biodistribution in mice, Chlorpyrifos was labeled with 131I using the Iodogen method. Biodistribution studies were carried out in KM mice. At different times after radiopharmaceutical i.v. administration (185 kBq 131I-Chlorpyrifos/mouse, n=5, the animals were sacrificed. Blood samples and the tissues of interested were collected, weighted and counted. The percentage of injected does per gram (%ID/g was calculated for each sample. The labeling yield of 131I-Chlorpyrifos was 93.5%, The radiochemical purity (RCP was 96.9%. Biodistribution in mice demonstrated that 131I-Chlorpyrifos was extensive, and the uptakes mainly occur in lung, stomach, small-intestine, colon, musle, and submaxillay gland, as indicated by their amount of 37.12%ID/g, 6.18%ID/g, 8.12%ID/g, 8.15%ID/g, 7.04%ID/g, and 7.02%ID/g at 10 min, respectively. And it was metabolized in liver and kidney, as indicated by their uptake of 4.34%ID/g and 8.50%ID/g at 5 min, and 0.22%ID/g and 0.69%ID/g at 4 h, respectively. In addition, 131I-Chlorpyrifos was cleared out from blood quickly, and the uptake of 131I-Chlorpyrifos in blood was 37.27%ID/g at 5 min, and decreased to 1.35%ID/g at 4 h post injection. In conclusion, 131I-Chlorpyrifos was stable in vitro and it was absorbed in lung and digestive tract, and it was metabolized mainly in liver and kidney, worthy of further investigation to trace the compound in vivo and in vitro.

  19. Biodistribution of radiolabelled human dendritic cells injected by various routes

    International Nuclear Information System (INIS)

    Quillien, Veronique; Moisan, Annick; Carsin, Andre; Lesimple, Thierry; Lefeuvre, Claudia; Bertho, Nicolas; Devillers, Anne; Toujas, Louis; Adamski, Henri; Leberre, Claudine

    2005-01-01

    The purpose of this study was to investigate the biodistribution of mature dendritic cells (DCs) injected by various routes, during a cell therapy protocol. In the context of a vaccine therapy protocol for melanoma, DCs matured with Ribomunyl and interferon-gamma were labelled with 111 In-oxine and injected into eight patients along various routes: afferent lymphatic vessel (IL) (4 times), lymph node (IN) (5 times) and intradermally (ID) (6 times). Scintigraphic investigations showed that the IL route allowed localisation of 80% of injected radioactivity in eight to ten nodes. In three cases of IN injection, the entire radioactivity stagnated in the injected nodes, while in two cases, migration to adjacent nodes was observed. This migration was detected rapidly after injection, as with IL injections, suggesting that passive transport occurred along the physiological lymphatic pathways. In two of the six ID injections, 1-2% of injected radioactivity reached a proximal lymph node. Migration was detectable in the first hour, but increased considerably after 24 h, suggesting an active migration mechanism. In both of the aforementioned cases, DCs were strongly CCR7-positive, but this feature was not a sufficient condition for effective migration. In comparison with DCs matured with TNF-α, IL-1β, IL-6 and PGE2, our DCs showed a weaker in vitro migratory response to CCL21, despite comparable CCR7 expression, and higher allostimulatory and TH1 polarisation capacities. The IL route allowed reproducible administration of specified numbers of DCs. The IN route sometimes yielded fairly similar results, but not reproducibly. Lastly, we showed that DCs matured without PGE2 that have in vitro TH1 polarisation capacities can migrate to lymph nodes after ID injection. (orig.)

  20. Biological Effects and Biodistribution of Bufotenine on Mice

    Directory of Open Access Journals (Sweden)

    Hugo Vigerelli

    2018-01-01

    Full Text Available Bufotenine is an alkaloid derived from serotonin, structurally similar to LSD and psilocin. This molecule is able to inhibit the rabies virus infection in in vitro and in vivo models, increasing the survival rate of infected animals. Being a very promising molecule for an incurable disease and because of the fact that there is no consensus regarding its neurological effects, this study aimed to evaluate chronic treatment of bufotenine on behavior, pathophysiology, and pharmacokinetics of mice. Animals were daily treated for 21 consecutive days with 0.63, 1.05, and 2.1 mg/animal/day bufotenine and evaluated by open field test and physiological parameters during all the experiment. After this period, organs were collected for histopathological and biodistribution analysis. Animals treated with bufotenine had mild behavioral alterations compared to the control group, being dose-response relationship. On the other hand, animals showed normal physiological functions and no histological alterations in the organs. With high doses, an inflammatory reaction was observed in the site of injection, but with no cellular damage. The alkaloid could be found in the heart and kidney with all doses and in the lungs and brain with higher doses. These results show that the effective dose, 0.63 mg/day, is safe to be administered in mice, since it did not cause significant effects on the animals’ physiology and on the CNS. Higher doses were well tolerated, causing only mild behavioral effects. Thus, bufotenine might be a drug prototype for rabies treatment, an incurable disease.

  1. Sex work: a comparative study.

    Science.gov (United States)

    McCarthy, Bill; Benoit, Cecilia; Jansson, Mikael

    2014-10-01

    Explanations of adult involvement in sex work typically adopt one of two approaches. One perspective highlights a variety of negative experiences in childhood and adolescence, including physical and sexual abuse, family instability, poverty, associations with "pimps" and other exploiters, homelessness, and drug use. An alternative account recognizes that some of these factors may be involved, but underscores the contribution of more immediate circumstances, such as current economic needs, human capital, and employment opportunities. Prior research offers a limited assessment of these contrasting claims: most studies have focused exclusively on people working in the sex industry and they have not assessed the independent effects of life course variables central to these two perspectives. We add to this literature with an analysis that drew on insights from life course and life-span development theories and considered the contributions of factors from childhood, adolescence, and adulthood. Our comparative approach examined predictors of employment in sex work relative to two other low-income service or care work occupations: food and beverage serving and barbering and hairstyling. Using data from a study of almost 600 workers from two cities, one in Canada and the other in the United States, we found that both immediate circumstances and negative experiences from early life are related to current sex work involvement: childhood poverty, abuse, and family instability were independently associated with adult sex work, as were limited education and employment experience, adult drug use, and marital status.

  2. Controlled Modulation of Serum Protein Binding and Biodistribution of Asymmetric Cyanine Dyes by Variation of the Number of Sulfonate Groups

    Directory of Open Access Journals (Sweden)

    Franziska M. Hamann

    2011-07-01

    Full Text Available To assess the suitability of asymmetric cyanine dyes for in vivo fluoro-optical molecular imaging, a comprehensive study on the influence of the number of negatively charged sulfonate groups governing the hydrophilicity of the DY-67x family of asymmetric cyanines was performed. Special attention was devoted to the plasma protein binding capacity and related pharmacokinetic properties. Four members of the DY-67x cyanine family composed of the same main chromophore, but substituted with a sequentially increasing number of sulfonate groups (n = 1−4; DY-675, DY-676, DY-677, DY-678, respectively, were incubated with plasma proteins dissolved in phosphate-buffered saline. Protein binding was assessed by absorption spectroscopy, gel electrophoresis, ultrafiltration, and dialysis. Distribution of dye in organs was studied by intraveneous injection of 62 nmol dye/kg body weight into mice (n = 12; up to 180 minutes postinjection using whole-body near-infrared fluorescence imaging. Spectroscopic studies, gel electrophoresis, and dialysis demonstrated reduced protein binding with increasing number of sulfonate groups. The bovine serum albumin binding constant of the most hydrophobic dye, DY-675, is 18 times higher than that of the most hydrophilic fluorophore, DY-678. In vivo biodistribution analysis underlined a considerable influence of dye hydrophilicity on biodistribution and excretion pathways, with the more hydrophobic dyes, DY-675 and DY-676, accumulating in the liver, followed by strong fluorescence signals in bile and gut owing to accumulation in feces and comparatively hydrophilic DY-678-COOH accumulating in the bladder. Our results demonstrate the possibility of selectively controlling dye-protein interactions and, thus, biodistribution and excretion pathways via proper choice of the fluorophore's substitution pattern. This underlines the importance of structure-property relationships for fluorescent labels. Moreover, our data could provide the

  3. The Label Matters: μPET Imaging of the Biodistribution of Low Molar Mass 89Zr and 18F-Labeled Poly(2-ethyl-2-oxazoline).

    Science.gov (United States)

    Glassner, Mathias; Palmieri, Luca; Monnery, Bryn D; Verbrugghen, Thomas; Deleye, Steven; Stroobants, Sigrid; Staelens, Steven; Wyffels, Leonie; Hoogenboom, Richard

    2017-01-09

    Poly(2-alkyl-2-oxazoline)s (PAOx) have received increasing interest for biomedical applications. Therefore, it is of fundamental importance to gain an in-depth understanding of the biodistribution profile of PAOx. We report the biodistribution of poly(2-ethyl-2-oxazoline) (PEtOx) with a molar mass of 5 kDa radiolabeled with PET isotopes 89 Zr and 18 F. 18 F-labeled PEtOx is prepared by the strain-promoted azide-alkyne cycloaddition (SPAAC) of [ 18 F]fluoroethylazide to bicyclo[6.1.0]non-4-yne (BCN)-functionalized PEtOx as many common labeling strategies were found to be unsuccessful for PEtOx. 89 Zr-labeled PEtOx is prepared using desferrioxamine end-groups as a chelator. Five kDa PEtOx shows a significantly faster blood clearance compared to PEtOx of higher molar mass while uptake in the liver is lower, indicating a minor contribution of the liver in excretion of the 5 kDa PEtOx. While [ 18 F]-PEtOx displays a rapid and efficient clearance from the kidneys, 5 kDa [ 89 Zr]-Df-PEtOx is not efficiently cleared over the time course of the study, which is most likely caused by trapping of 89 Zr-labeled metabolites in the renal tubules and not the polymer itself, demonstrating the importance of selecting the appropriate label for biodistribution studies.

  4. Preparation and biodistribution of radiolabeled fullerene C60 nanocrystals

    International Nuclear Information System (INIS)

    Nikolic, Nadezda; Vranjes-Duric, Sanja; Jankovic, Drina; Dokic, Divna; Mirkovic, Marija; Bibic, Natasa; Trajkovic, Vladimir

    2009-01-01

    The present study describes for the first time a procedure for the radiolabeling of fullerene (C 60 ) nanocrystals (nanoC 60 ) with Na 125 I, as well as the biodistribution of radiolabeled nanoC 60 ( 125 I-nanoC 60 ). The solvent exchange method with tetrahydrofuran was used to make colloidal water suspensions of radiolabeled nanoC 60 particles. The radiolabeling procedure with the addition of Na 125 I to tetrahydrofuran during dissolution of C 60 gave a higher radiochemical yield of radiolabeled nanoC 60 particles in comparison to the second option, in which Na 125 I was added after C 60 was dissolved. Using photon correlation spectroscopy and transmission electron microscopy, 125 I-nanoC 60 particles were found to have a crystalline structure and a mean diameter of 200-250 nm. The 125 I-nanoC 60 had a particularly high affinity for human serum albumin, displaying 95% binding efficiency after 1 h. Biodistribution studies of 125 I-nanoC 60 in rats indicated significant differences in tissue accumulation of 125 I-nanoC 60 and the radioactive tracer Na 125 I. The higher accumulation of radiolabeled nanoC 60 was observed in liver and spleen, while accumulation in thyroid, stomach, lungs and intestines was significantly lower in comparison to Na 125 I. In addition to being useful for testing the biological distribution of nanoC 60 , the described radiolabeling procedure might have possible applications in cancer radiotherapy.

  5. In vitro evaluation, biodistribution and scintigraphic imaging in mice of radiolabeled anthrax toxins

    International Nuclear Information System (INIS)

    Dadachova, Ekaterina; Rivera, Johanna; Revskaya, Ekaterina; Nakouzi, Antonio; Cahill, Sean M.; Blumenstein, Michael; Xiao, Hui; Rykunov, Dmitry; Casadevall, Arturo

    2008-01-01

    Introduction: There is a lot of interest towards creating therapies and vaccines for Bacillus anthracis, a bacterium which causes anthrax in humans and which spores can be made into potent biological weapons. Systemic injection of lethal factor (LF), edema factor (EF) and protective antigen (PA) in mice produces toxicity, and this protocol is commonly used to investigate the efficacy of specific antibodies in passive protection and vaccine studies. Availability of toxins labeled with imageable radioisotopes would allow to demonstrate their tissue distribution after intravenous injection at toxin concentration that are below pharmacologically significant to avoid masking by toxic effects. Methods: LF, EF and PA were radiolabeled with 188 Re and 99m Tc, and their performance in vitro was evaluated by macrophages and Chinese hamster ovary cells toxicity assays and by binding to macrophages. Scintigraphic imaging and biodistribution of intravenously (IV) injected 99m Tc-and 123 I-labeled toxins was performed in BALB/c mice. Results: Radiolabeled toxins preserved their biological activity. Scatchard-type analysis of the binding of radiolabeled PA to the J774.16 macrophage-like cells revealed 6.6x10 4 binding sites per cell with a dissociation constant of 6.7 nM. Comparative scintigraphic imaging of mice injected intravenously with either 99m Tc-or 123 I-labeled PA, EF and LF toxins demonstrated similar biodistribution patterns with early localization of radioactivity in the liver, spleen, intestines and excretion through kidneys. The finding of renal excretion shortly after IV injection strongly suggests that toxins are rapidly degraded which could contribute to the variability of mouse toxigenic assays. Biodistribution studies confirmed that all three toxins concentrated in the liver and the presence of high levels of radioactivity again implied rapid degradation in vivo. Conclusions: The availability of 188 Re and 99m Tc-labeled PA, LF and EF toxins allowed us to

  6. Biodistribution, kinetics, and biological fate of SPION microbubbles in the rat

    Directory of Open Access Journals (Sweden)

    Barrefelt A

    2013-08-01

    Full Text Available Åsa Barrefelt,1,2,* Maryam Saghafian,2,* Raoul Kuiper,3 Fei Ye,4 Gabriella Egri,5 Moritz Klickermann,5 Torkel B Brismar,1 Peter Aspelin,1 Mamoun Muhammed,4 Lars Dähne,5 Moustapha Hassan2,6 1Department of Clinical Science, Intervention and Technology, Division of Medical Imaging and Technology, Karolinska Institutet, and Department of Radiology, Karolinska University Hospital-Huddinge, Stockholm, Sweden; 2Experimental Cancer Medicine, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden; 3Karolinska Institute Core Facility for Morphologic Phenotype Analysis, Clinical Research Center, Karolinska University Hospital-Huddinge, Stockholm, Sweden; 4Division of Functional Materials, Department of Materials and Nano Physics, Royal Institute of Technology, Stockholm, Sweden; 5Surflay Nanotec GmbH, Berlin, Germany; 6Clinical Research Center, Karolinska University Hospital-Huddinge, Stockholm, Sweden *These authors contributed equally to this work Background: In the present investigation, we studied the kinetics and biodistribution of a contrast agent consisting of poly(vinyl alcohol (PVA microbubbles containing superparamagnetic iron oxide (SPION trapped between the PVA layers (SPION microbubbles. Methods: The biological fate of SPION microbubbles was determined in Sprague-Dawley rats after intravenous administration. Biodistribution and elimination of the microbubbles were studied in rats using magnetic resonance imaging for a period of 6 weeks. The rats were sacrificed and perfusion-fixated at different time points. The magnetic resonance imaging results obtained were compared with histopathologic findings in different organs. Results: SPION microbubbles could be detected in the liver using magnetic resonance imaging as early as 10 minutes post injection. The maximum signal was detected between 24 hours and one week post injection. Histopathology showed the presence of clustered SPION microbubbles predominantly in the lungs from

  7. Macroscopic and microscopic biodistribution of intravenously administered iron oxide nanoparticles

    Science.gov (United States)

    Misra, Adwiteeya; Petryk, Alicia A.; Strawbridge, Rendall R.; Hoopes, P. Jack

    2015-03-01

    Iron oxide nanoparticles (IONP) are being developed for use as a cancer treatment. They have demonstrated efficacy when used either as a monotherapy or in conjunction with conventional chemotherapy and radiation. The success of IONP as a therapeutic tool depends on the delivery of a safe and controlled cytotoxic thermal dose to tumor tissue following activation with an alternating magnetic field (AMF). Prior to clinical approval, knowledge of IONP toxicity, biodistribution and physiological clearance is essential. This preliminary time-course study determines the acute toxicity and biodistribution of 110 nm dextran-coated IONP (iron) in mice, 7 days post systemic, at doses of 0.4, 0.6, and 1.0 mg Fe/ g mouse bodyweight. Acute toxicity, manifested as changes in the behavior of mice, was only observed temporarily at 1.0 mg Fe/ g mouse bodyweight, the highest dose administered. Regardless of dose, mass spectrometry and histological analysis demonstrated over 3 mg Fe/g tissue in organs within the reticuloendotheilial system (i.e. liver, spleen, and lymph nodes). Other organs (brain, heart, lungs, and kidney) had less than 0.5 mg Fe/g tissue with iron predominantly confined to the organ vasculature.

  8. 99mTc-tetrapeptides: radiolabelling and biodistribution in rats

    International Nuclear Information System (INIS)

    Laznickova, A.; Laznicek, M.; Trejtnar, F.; Mather, S.J.

    1998-01-01

    Preparation of 99m Tc-labelled tetrapeptides, namely acetyl-Gly-Gly-Cys-Gly (I), acetyl-Ser-Ser-Cys-Gly (II) and acetyl-Gly-Gly-Cys-Lys (III), analysis of their radiochemical purity and biodistribution were investigated in rats. The aim was to determine the relationship between structure and biological behaviour of 99m Tc-labelled peptides which are formed by amino-acid sequences capable of chelating technetium useful as universal chelators in ''hybrid'' peptides composed of receptor-specific part and the part chelating technetium. For labelling with 99m Tc, a conventional transchelation from 99m Tc-gluconate was used and radiolabelled peptides were purified by filtration on Whatman microfilters 12 kD. Radiochemical purity was higher than 98%. Biodistribution studies in rats showed that all agents are rapidly cleared from the body mostly via urine, but some part of administered radioactivity also in the faces was found. The later route of elimination way increased in the order III 99m Tc-MAG3. The results obtained will assist with design of optimal biocompatible tetrapeptides as chelators for formation of hybrid receptor-specific peptides. (author)

  9. Drugs that alter biodistribution and kinetics of radiopharmaceuticals

    International Nuclear Information System (INIS)

    Shani, J.

    1986-01-01

    Target localization and organ biodistribution of radiopharmaceuticals (RPs) may be altered by non-radioactive drugs whose pharmacological mechanisms compete with the RPs for the same retention processes. Originally referred to as side effects or incompatibilities, such interactions became a major concern in evaluating Nuclear Medicine procedures, as they might cause interpretation of the latter to be without value or misleading. With accumulated experience, some interactions were intentionally included in Nuclear Medicine procedures and became an additional tool in differential diagnosis. Moreover, due to the ability of some RPs to compete with therapeutic agents, Nuclear Medicine studies shifted from anatomical-physiological to more pharmacologically-pathologically-based procedures that can also monitor the stage of disease, and follow its treatment. The aim of this review, therefore, is not only to illustrate some crucial pharmacological issues in Nuclear Medicine imaging, but to emphasize the possible input that alterations of RP biodistribution by drugs may have in achieving better and safer diagnosis, disease staging and monitoring of the patient's response to therapy. 166 references

  10. Biodistribution and human dosimetry estimation of fluoro-L-DOPA as PET imaging agent of dopaminergic nerve transmitter systems

    International Nuclear Information System (INIS)

    Tang Ganghua; Wang Mingfang; Luo Lei; Gan Manquan; Tang Xiaolan; Zhang Lan; Wang Yongxian

    2002-01-01

    Objective: To investigate the biodistribution and human dosimetry estimation of 6-[ 18 F] Fluoro-L-DOPA (FDOPA). Methods: Biodistribution of FDOPA in normal rats and brain of hemi-Parkinsonism rats were determined. Human dosimetry estimation was performed by MIRD method based on the rats biodistribution data. Results: Biodistributions in normal rats showed high uptake in kidney, blood, striatum and hippocampi, fast clearance of radioactivity from kidney and blood, longer retain time in striatum and hippocampi, and higher striatum to cerebellum and striatum to cortex ratio. FDOPA uptake, striatum to cerebellum and striatum to cortex ratio in the lesioned side of hemi-Parkinsonism rats (P 2 to 2.3 x 10 -2 mGy/MBq and the effective dose in humans was estimated to be 2.05 x 10 -2 mSv/MBq after injection of FDOPA based on rats biodistribution data, which were consistent with those reported by literature on the whole. Conclusion: Human radiation dosimetry of FDOPA and other PET tracers can be estimated based on animals biodistribution data. The synthetic FDOPA is safe and efficient and can be used in animals, human and PD patients PET studies

  11. Pharmacokinetics and biodistribution of 11C-HupA in the normal animal

    International Nuclear Information System (INIS)

    Yan Jin; Guan Yihui; Xue Fangping; Zhang Zhenwen; Liu Ping; Lin Yiangtong

    2009-01-01

    Objective: Hula is one of the potential drugs which can be used to treat Alzheimer's disease (Ad). The aim of this study was to explore the pharmacokinetics and biodistribution of Hula in vivo by using 11 C-Hula. Methods: A total of 25 Sd rats were studied. They were divided into 5 groups (5 rats in each group). All had intravenous injection of 22 MBq (in 0.2 ml) 11 C-Hula through tail vein. Dynamic imaging Was acquired from 5 to 90 minutes after injection. Venous blood and organ activities were collected at 5, 15, 30, 60. and 90 minutes after injection. Percentage activity of injected dose per gram of tissue (%ID/g) was calculated to characterize the biodistribution of tracer in different brain regions: frontal,apical, temporal, occipital, cerebellum, hippocampus, striatum, thalamencephalon, and brain stem, Variance analysis using SPSS 11.5 software was performed and compared among the study groups. Results: 11 C-HupA was characteristic for its quick clearance from blood, with half time T 1/2 of (14.61 ± 1.77) min, and clearance rate (CL) of (0.12 ± 0.01) ml · min -1 · kg -1 . Metabolism was through liver, and excretion through kidney. Pharmacokinetics of 11 C-HupA in rats corresponded to a one-compartment model. with an activity curve (area under curve, AUC) 0-8 integral of (167.57 ± 12.39) ml · min -1 · kg -1 . There was significant difference of 11 C-HupA distribution in different brain regions, being greater in cerebral cortex, hippocampus, hypothalamus and brain stem. Conclusions: Pharmacokinetic study of 11 C-HupA in brain was fast. convenient and showed high specificity and sensitivity. Its ability to quantitatively evaluate brain function and its characteristic distribution in mice provided some evidence for monitoring therapy in AD patients. (authors)

  12. Biodistribution and Pharmacokinetics Study of siRNA-loaded Anti-NTSR1-mAb-functionalized Novel Hybrid Nanoparticles in a Metastatic Orthotopic Murine Lung Cancer Model

    Directory of Open Access Journals (Sweden)

    Maryna Perepelyuk

    2016-01-01

    Full Text Available Small interfering RNA (siRNA is effective in silencing critical molecular pathways in cancer. The use of this tool as a treatment modality is limited by lack of an intelligent carrier system to enhance the preferential delivery of this molecule to specific targets in vivo. In the present study, the in vivo behavior of novel anti-NTSR1-mAb-functionalized antimutant K-ras siRNA-loaded hybrid nanoparticles, delivered by i.p. injection to non-small-cell lung cancer in mice models, was investigated and compared to that of a naked siRNA formulation. The siRNA in anti-NTSR1-mAb-functionalized hybrid nanoparticles was preferentially accumulated in tumor-bearing lungs and metastasized tumor for at least 48 hours while the naked siRNA formulation showed lack of preferential accumulation in all of the organs monitored. The plasma terminal half-life of nanoparticle-delivered siRNA was 11 times higher (17–1.5 hours than that of the naked siRNA formulation. The mean residence time and AUClast were 3.4 and 33 times higher than the corresponding naked siRNA formulation, respectively. High-performance liquid chromatography analysis showed that the hybrid nanoparticle carrier system protected the encapsulated siRNA against degradation in vivo. Our novel anti-NTSR1-mAb-functionalized hybrid nanoparticles provide a useful platform for in vivo targeting of siRNA for both experimental and clinical purposes.

  13. Enhanced delivery of iodine for synchrotron stereotactic radiotherapy by means of intracarotid injection and blood-brain barrier disruption: Quantitative iodine biodistribution studies and associated dosimetry

    International Nuclear Information System (INIS)

    Adam, Jean-Francois; Biston, Marie-Claude; Joubert, Aurelie; Charvet, Anne-Marie; Le Bas, Jean-Francois; Esteve, Francois; Elleaume, Helene

    2005-01-01

    Purpose: Synchrotron stereotactic radiotherapy (SSR) is a binary cancer treatment modality that involves the selective accumulation of a high Z element, such as iodine, in tumors, followed by stereotactic irradiation with kilovoltage X-rays from a synchrotron source. The success of SSR is directly related to the absolute amount of iodine achievable in the tumor. The purposes of this preclinical study were to determine whether the delivery of iodine to brain tumor models in rats could be enhanced by the means of its intracarotid injection with or without a hyperosmotic solution and to evaluate corresponding absorbed X-ray doses. Methods and materials: Experiments were performed on four groups of F98 glioma-bearing rats, which received either intracarotid (IC) or intravenous (IV) infusions of a mixture (6 mL in 12 min) of an iodinated contrast agent associated or not with a transient blood-brain barrier opener (mannitol). The mixture volumetric proportions were 8/13 of Iomeron (C = 350 mg/mL) for 5/13 of mannitol or saline, respectively. Absolute iodine concentration kinetic was measured in vivo in the tumor, blood, contralateral and ipsilateral brain, and muscle by monochromatic computed tomography. Associated dosimetry was performed by computing the iodine dose enhancement factor (DEF) in each region and building dose distribution maps by analytical simulations. Results: Infusion of mannitol significantly enhanced iodine tumor uptake compared with the control values (p < 0.0001 and p = 0.0138, for IC and IV protocols, respectively). The mean iodine concentrations (C) reached 20.5 ± 0.98 mg/mL (DEF = 4.1) after administration of iodine and mannitol vs. 4.1 ± 1.2 mg/mL i.c. with serum (DEF = 1.6). The tumor iodine uptakes after jugular injection with mannitol (C = 4.4 ± 2.1 mg/mL, DEF = 1.7) were not significantly different from IC injection of iodine without mannitol (p = 0.8142). The IV injection of iodine with saline led to an iodine concentration in the tumor

  14. Biodistribution of Yttrium-90-Labeled Anti-CD45 Antibody in a Nonhuman Primate Model

    International Nuclear Information System (INIS)

    Nemecek, Eneida; Hamlin, Donald K.; Fisher, Darrell R.; Krohn, Kenneth A.; Pagel, John M.; Applebaum, F. R.; Press, Oliver W.; Matthews, Dana C.

    2005-01-01

    Radioimmunotherapy may improve the outcome of hematopoietic cell transplantation for hematologic malignancies by delivering targeted radiation to hematopoietic organs while relatively sparing nontarget organs. We evaluated the organ localization of yttrium-90-labeled anti-CD45 (90Y-anti-CD45) antibody in macaques, a model that had previously predicted iodine-131-labeled anti-CD-45 (131I-anti-CD45) antibody biodistribution in humans. Experimental Design: Twelve Macaca nemestrina primates received anti-CD45 antibody labeled with 1 to 2 mCi of 90Y followed by serial blood sampling and marrow and lymph node biopsies, and necropsy. The content of 90Y per gram of tissue was determined by liquid scintillation spectrometry. Time-activity curves were constructed using average isotope concentrations in each tissue at measured time points to yield the fractional residence time and estimate radiation absorbed doses for each organ per unit of administered activity. The biodistribution of 90Y-anti-CD45 antibody was then compared with that previously obtained with 131I-anti-CD45 antibody in macaques. Results: The spleen received 2,120, marrow 1,060, and lymph nodes 315 cGy/mCi of 90Y injected. The liver and lungs were the nontarget organs receiving the highest radiation absorbed doses (440 and 285 cGy/mCi, respectively). Ytrrium-90-labeled anti-CD45 antibody delivered 2.5- and 3.7-fold more radiation to marrow than to liver and lungs, respectively. The ratios previously observed with 131I-antiCD45 antibody were 2.5-and 2.2-fold more radiation to marrow than to liver and lungs, respectively. Conclusions: This study shows that 90Y-anti-CD45 antibody can deliver relatively selective radiation to hematopoietic tissues, with similar ratios of radiation delivered to target versus nontarget organs, as compared with the 131I immunoconjugate in the same animal model

  15. Comparative study Beamnrc VS Pinnacle

    International Nuclear Information System (INIS)

    Moreno Reyes, J. C.; Macias Jaen, J.; Jimenez Ortega, E.

    2013-01-01

    Has been developed in JAVA a software application called JJGAMMA, capable of manipulating the environment BEAMNRC and Pinnacle output formats 3 , comfortable, fast and accurately. As particular application you can use to compare dose distributions (plans for treatments, checking fields for modeling and clinical accelerators Commissioner) using, as objective criteria, function or Gamma index. (Author)

  16. Paracetamol suppositories: a comparative study.

    Science.gov (United States)

    Cullen, S; Kenny, D; Ward, O C; Sabra, K

    1989-01-01

    Paracetamol suppositories in two different bases were given to children who had fever after operations. Plasma concentrations and the effect on temperature were compared. There was a significant correlation between peak plasma concentrations and maximum drop in temperature. A lipophilic base produced better results than a hydrophilic base. PMID:2817936

  17. Paracetamol suppositories: a comparative study.

    OpenAIRE

    Cullen, S; Kenny, D; Ward, O C; Sabra, K

    1989-01-01

    Paracetamol suppositories in two different bases were given to children who had fever after operations. Plasma concentrations and the effect on temperature were compared. There was a significant correlation between peak plasma concentrations and maximum drop in temperature. A lipophilic base produced better results than a hydrophilic base.

  18. Effects of broccoli extract on biodistribution and labeling blood components with 99mTc-GH

    International Nuclear Information System (INIS)

    Cekic, Betul; Muftuler, Fazilet Zumrut Biber; Kilcar, Ayfer Yurt; Ichedef, Cigdem; Unak, Perihan

    2011-01-01

    Purpose: people consume vegetables without the knowledge of the side effects of the biological and chemical contents and interactions between radiopharmaceuticals and herbal extract. To this end, current study is focused on the effects of broccoli extract on biodistribution of radiolabeled glucoheptonate ( 99m Tc-GH) and radiolabeling of blood components. Methods: GH was labeled with 99m Tc. Quality control studies were done utilizing TLC method. Biodistribution studies were performed on male rats which were treated via gavage with either broccoli extract or SF as control group for 15 days. Blood samples were withdrawn from rats' heart. Radiolabeling of blood constituents performed incubating with GH, SnCl 2 and 99m Tc. Results: radiochemical yield of 99m Tc-GH is 98.46±1.48 % (n=8). Biodistribution studies have shown that according to the control, the treated group with broccoli has approximately 10 times less uptake in kidney. The percentage of the radioactivity ratios of the blood components is found to be same in both groups. Conclusions: although there is no considerable effect on the radiolabeling of blood components, there is an outstanding change on the biodistribution studies especially on kidneys. The knowledge of this change on kidney uptake may contribute to reduce the risk of misdiagnosis and/or repetition of the examinations in Nuclear Medicine. (author)

  19. Effect of carrier on labeling and biodistribution of Re-188-Hydroxyethylidene diphosphonate

    International Nuclear Information System (INIS)

    Chang, Young Soo; Jeong, Jae Min; Kim, Bo Kwang; Cho, Jung Hyuk; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Lee, Seung Jin; Jin, Ren Jie; Lee, Sang Eun

    2000-01-01

    Re-188-Hydroxyethylidene diphosphonate (HEDP) is a new cost-effective agent for systemic radioisotope therapy of metastatic bone pain. We investigated the influence of carrier for labeling and biodistribution of Re-188-HEDP using HEDP kit with or without carrier (KReO 4 ). The kits (HEDP 15 mg, gentisic acid 4 mg and SnC1 2 .2H 2 O 4.5 mg) with or without carrier (KReO 4 0.1 mg) were labeled with Re-188 solution, made available from an in-house generator by boiling for 15 min. We compared the labeling efficiency and stability of carrier-added and carrier-free preparations of Re-188-HEDP. Biodistribution and imaging studies of each preparation were performed in ICR mice (1.85-3.7 MBq/0.1 ml) and SD rats (74.1-85.2 MBq/0.5 ml). The carrier-added preparation showed high labeling efficiency (95% at pH 5) and high stability in serum (88%, 3hr). However, the carrier-free preparation showed low labeling efficiency (59% at pH 5) and low stability (43%, 3 hr). The carrier-added preparation showed high uptake in bone and low uptake in stomach and kidneys. However, the carrier-free preparation showed lower uptake in bone and higher uptake in both stomach and kidneys, which is supposed to be due to released perrhenate. The carrier-added preparation also showed better images with higher skeletal accumulation, lower uptake in other organs and lower soft tissue uptake than the carrier-free preparation. The results of these studies clearly demonstrate that addition of carrier perrhenate is required for high labeling efficiency, stability, bone uptake and good image quality of Re-188-HEDP.=20

  20. Preparation and biodistribution of 99Tcm-lomefloxacin in inflammatory model mice

    International Nuclear Information System (INIS)

    Liu Jianfeng; Han Jiankui; Zhang Chao; Hou Guihua

    2009-01-01

    Objective: The study of 99 TC m -ciprofloxacin, a fluoroquinolones antibiotic, as a tracer for infection and inflammation imaging has been reported. The aim of this study was to investigate the radio-labeling and biodistribution of lomefloxacin (fluoroquinolones analogue) as an inflammatory imaging agent. Methods: 99 TC m -lomefloxacin was prepared and it underwent quality control with thin layer chromatography (TLC). The different labeling conditions were compared. The radiochemical purity, labeling efficiency, stability and lipid/water partition coefficient of 99 TC m -lomefloxacin were measured. The binding activities of 99 TC m -lomefloxacin with Staphylococci aureus (S. aureus)in vitro were tested. 99 TC m -lomefloxacin was in-ieeted through tail vein in the S. aureus-induced inflammatory model mice. The mice were sacrificed and their blood. inflammatory muscles. major organs were taken out at different time after tracer inieetion. Then the radioactivity count of these samples was measured to observe biodistribution. Whole-body radioauto-graphic images were obtained with storage phosphor screen system. Variance analysis using Concise Statis-tics 10.3 software was performed. Results: 99 TC m -lomefloxacin was lipid-soluble with labeling efficiency of 97.5%. The radiochemieal purity was more than 95% at 6 h after storing in room temperature. In vitro test 99 TC m -lomefloxacin showed good binding characteristic with S. auaresu and was positively correlated with the colony number of S. aureus. The highest binding appeared at 1 h. In vivo 99 TC 5 m-lomefloxacin apparently accumulated in inflammatory tissues at 2 h after tracer injection with the uptake ratio of 4.07 ± 1.05 in inflammatory muscles to control muscles. Whole-body autoradiography showed that all inflammation foci were visualized. Conclusion: 99 TC m -lomefloxacin may be a novel potential agent for inflammatory imaging. (authors)

  1. Preparation, chromatographic evaluation and biodistribution of {sup 99m}Tc-procainamide as a radiopharmaceutical for heart imaging

    Energy Technology Data Exchange (ETDEWEB)

    Motaleb, M.A.; Ibrahim, I.T.; Abo Rizq, R.S. [Atomic Energy Authority, Cairo (Egypt). Labeled Compound Dept.; Elzanfaly, E.S. [Cairo Univ. (Egypt). Analytical Dept.

    2017-06-01

    Procainamide (4-amino-N-[2-(diethylamino) ethyl] benzamide) is a sodium channel blocker, which acts as an effective antiarrhythmic agent used in the treatment of a variety of atrial and ventricular arrhythmias. The aim of this study was to prepare {sup 99m}Tc-procainamide complex, apply different chromatographic techniques for the assay of radiolabeling yield and study its biodistribution as a novel radiopharmaceutical for heart imaging. {sup 99m}Tc-procainamide was obtained with a maximum labeling yield of 95.76±0.20% via direct labeling method under optimum conditions of 200 μg of procainamide, 300 μL of buffer (carbonate) at pH 11, 30 μg SnCl{sub 2} . 2H{sub 2}O at room temperature (25 C) for 15 min. In terms of in vitro stability, the complex was stable for 3 h. Chromatographic evaluation using paper chromatography, thin layer chromatography, gel chromatography, and high performance liquid chromatography showed reliable results for measuring the radiochemical yield. Biodistribution study of {sup 99m}Tc-procainamide showed ratios of heart/lung and heart/liver (6.38±1.50, 2.06±0.31, respectively at 30 min post injection) which was comparable to that of {sup 99m}Tc-sestamibi (7.4±2.00, 0.97±0.10, respectively at 60 min, P<0.05).

  2. Preparation, chromatographic evaluation and biodistribution of "9"9"mTc-procainamide as a radiopharmaceutical for heart imaging

    International Nuclear Information System (INIS)

    Motaleb, M.A.; Ibrahim, I.T.; Abo Rizq, R.S.; Elzanfaly, E.S.

    2017-01-01

    Procainamide (4-amino-N-[2-(diethylamino) ethyl] benzamide) is a sodium channel blocker, which acts as an effective antiarrhythmic agent used in the treatment of a variety of atrial and ventricular arrhythmias. The aim of this study was to prepare "9"9"mTc-procainamide complex, apply different chromatographic techniques for the assay of radiolabeling yield and study its biodistribution as a novel radiopharmaceutical for heart imaging. "9"9"mTc-procainamide was obtained with a maximum labeling yield of 95.76±0.20% via direct labeling method under optimum conditions of 200 μg of procainamide, 300 μL of buffer (carbonate) at pH 11, 30 μg SnCl_2 . 2H_2O at room temperature (25 C) for 15 min. In terms of in vitro stability, the complex was stable for 3 h. Chromatographic evaluation using paper chromatography, thin layer chromatography, gel chromatography, and high performance liquid chromatography showed reliable results for measuring the radiochemical yield. Biodistribution study of "9"9"mTc-procainamide showed ratios of heart/lung and heart/liver (6.38±1.50, 2.06±0.31, respectively at 30 min post injection) which was comparable to that of "9"9"mTc-sestamibi (7.4±2.00, 0.97±0.10, respectively at 60 min, P<0.05).

  3. Effect of carrier on labeling and biodistribution of Re-188-hydroxyethylidene disphosphonate (HEDP)

    International Nuclear Information System (INIS)

    Jang, Y. S.; Jeong, J. M.; Kim, B. K.; Lee, D. S.; Jeong, J. K.; Lee, M. C.; Cho, J. H.

    1998-01-01

    Re-188- hydroxyethylidene disphosphonate (HEDP) is a new cost-effective agent for systemic radioisotope therapy of metastatic bone pain. We investigated the influence of carrier for labeling and biodistribution of Re-188-HEDP using HEDP kit(HEDP 15 mg, gentisic acid 4 mg and SnCl 2 2H 2 O 4.5 mg) with or without carrier (KReO 4 0.1 mg). The kits labeled with Re-188 solution available from an in-house generator by boiling for 15 min. The generator provides high 70-80 % equil yields and has an indefnite self-life. We compared the stability of carrier-added(CA) and carrier-free(CF) preparations of Re-188-HEDP. Biodistribution and imaging studies of each preparation were performed in ICR mice(1.85-3.7 MBq/0.1 ml) and SD rats(74.1-85.2 MBq/0.5 ml). The CA preparation showed high labeling efficiency(95% at pH 5) and high stability in serum(88%, 3 hr). However, the CF preparation showed low labeling efficiency(59% at pH 5) and low stability(43%, 3 hr). The CA preparation showed high uptake in bone and low uptake in stomach and kidneys. However, the CF preparation showed lower uptake in bone and higher uptake in both stomach and kidney, which is supposed to be due to released perrhenate. The CA preparation also showed better images with higher skeletal accumulation, lower uptake in other organs and lower soft tissue uptake than the CF preparation of carrier perrhenate is required for high labeling efficiency, stability, bone uptake and good image quality of Re-188-HEDP

  4. Benchmarked Library Websites Comparative Study

    KAUST Repository

    Ramli, Rindra M.; Tyhurst, Janis

    2015-01-01

    This presentation provides an analysis of services provided by the benchmarked library websites. The exploratory study includes comparison of these websites against a list of criterion and presents a list of services that are most commonly deployed by the selected websites. In addition to that, the investigators proposed a list of services that could be provided via the KAUST library website.

  5. COMPARATIVE STUDY ON CORPORATE GOVERNANCE

    Directory of Open Access Journals (Sweden)

    Gavrea Corina

    2011-12-01

    Full Text Available Corporate governance is a key element of today’s economic reality being more and more present in many countries around the world. This paper has two main objectives. The first one is to offer more insight into the concept of corporate governance by a thorough literature review and by presenting and analyzing a framework of corporate governance. The second objective of this paper is to investigate the corporate governance situation in three developing economies (Romania, Bulgaria and Hungary. The World Bank and the European Bank for Reconstruction and Development published a series of reports on corporate governance. The present study uses data from these reports in order to illustrate how these developing economies are dealing with corporate governance. Based on ROSC Reports a corporate governance score was calculated. As this score shows, there is room for improvement for all three developing economies. This study is important because it shows the differences in corporate governance among developing economies and the need to study these nations at the individual country level. Corporate governance has many benefits for developing economies. It helps developing economies to register sustainable growth rates, to increases investors’ confidence in the national economy, and to increase the ability of capital markets to mobilize savings.

  6. Biodistribution of 212Pb Conjugated Trastuzumab in Mice

    International Nuclear Information System (INIS)

    Schneider, N.; Lobaugh, M.; Sandwall, P.; Glover, S.; Murry, M.; Dong, Z.; Spitz, H.

    2014-01-01

    Clinical use of radiolabeled monoclonal antibodies in therapeutic treatment of cancer is increasing. This study demonstrates an increased uptake rate in the tumor over a 72 hr period of observation following a single intravenous injection of 212Pb-trastuzumab in mice. Whereas 212Pb-trastuzumab appeared not to cause systemic toxicity4, there may be concomitant uptake in other organs that should be considered in evaluating the risk of radiation toxicity associated with therapy. Additional laboratory and clinical study with 212Pb-trastuzumab should be conducted to define an optimized therapeutic strategy and determine the radiation doses delivered to non-targeted organs and tissues using microdosimetry methods. Results of this biodistribution study support further investigation of radiolabeled 212Pb-TCMC-trastuzumab, radiobiological organ microdosimetry, and optimal dosing regimens for 212Pb-trastuzumab as a therapeutic agent

  7. Biodistribution, toxicity and radiation dosimetry studies of the serotonin transporter radioligand 4-[{sup 18}F]-ADAM in rats and monkeys

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Ya-Yao [Tri-Service General Hospital, PET Center, Department of Nuclear Medicine, Taipei (China); National Tsing Hua University, Department of Biomedical Engineering and Environmental Sciences, Hsinchu (China); Ma, Kuo-Hsing [National Defense Medical Center, Department of Biology and Anatomy, Taipei (China); Tseng, Ta-Wei; Chou, Ta-Kai; Huang, Wen-Sheng [Tri-Service General Hospital, PET Center, Department of Nuclear Medicine, Taipei (China); Ng, Hanna; Mirsalis, Jon C. [SRI International, Menlo Park, CA (United States); Fu, Ying-Kai [Institute of Nuclear Energy Research, Taoyuan (China); Chung Yuan Christian University, Department of Chemistry, Chung-Li (China); Chu, Tieh-Chi [National Tsing Hua University, Department of Biomedical Engineering and Environmental Sciences, Hsinchu (China); Yuanpei University, Department of Radiological Technology, Hsinchu (China); Shiue, Chyng-Yann [Tri-Service General Hospital, PET Center, Department of Nuclear Medicine, Taipei (China); University of Pennsylvania, Department of Radiology, Philadelphia, PA (United States)

    2010-03-15

    4-[{sup 18}F]-ADAM is a potent serotonin transport imaging agent. We studied its toxicity in rats and radiation dosimetry in monkeys before human studies are undertaken. Single and multiple-dosage toxicity studies were conducted in Sprague-Dawley rats. Male and female rats were injected intravenously with 4-F-ADAM as a single dose of 1,023.7 {mu}g/kg (1,000 times the human dose) or as five consecutive daily doses of 102.37 {mu}g/kg (100 times the human dose). PET/CT scans were performed in seven Formosa Rock monkeys (four males and three females) using a Siemens Biograph scanner. After injection of 4-[{sup 18}F]-ADAM (182{+-}8 MBq), a low dose CT scan and a series of eight whole-body PET scans were performed. Whole-body images were acquired in 3-D mode. Time-activity data of source organs were used to calculate the residence times and estimate the absorbed radiation dose using OLINDA/EXM software. In the rats neither the single dose nor the five daily doses of 4-F-ADAM produced overt adverse effects clinically. In the monkeys the radiation doses received by most organs ranged between 7.1 and 35.7 {mu}Gy/MBq, and the urinary bladder was considered to be the critical organ. The effective doses extrapolated to male and female adult humans were 17.4 and 21.8 {mu}Sv/MBq, respectively. Toxicity studies in Sprague-Dawley rats and radiation dosimetry studies in Formosa Rock monkeys suggested that 4-[{sup 18}F]-ADAM is safe for use in human PET imaging studies. (orig.)

  8. Comparative study of Butterfly valves

    International Nuclear Information System (INIS)

    Galmes Belmonte, F.B.

    1998-01-01

    This work tries to justify the hydrodynamic butterfly valves performance, using the EPRI tests, results carried out in laboratory and in situ. This justification will be possible if: - The valves to study are similar - Their performance is calculated using EPRI's methodology Looking for this objective, the elements of the present work are: 1. Brief EPRI butterfly valve description it wild provide the factors which are necessary to define the butterfly valves similarity. 2. EPRI tests description and range of validation against test data definition. 3. Description of the spanish butterfly analyzed valves, and comparison with the EPRI performance results, to prove that this valves are similar to the EPRI test valves. In this way, it will not be necessary to carry out particular dynamic tests on the spanish valves to describe their hydrodynamic performance. (Author)

  9. Effects of concurrent drug therapy on technetium /sup 99m/Tc gluceptate biodistribution

    International Nuclear Information System (INIS)

    Hinkle, G.H.; Basmadjian, G.P.; Peek, C.; Barker, K.K.; Ice, R.D.

    1982-01-01

    Drug interactions with /sup 99m/Tc gluceptate resulting in altered biodistribution were studied using chart review and animal tests. Charts of nine patients who had abnormal gallbladder uptake of technetium /sup 99m/Tc gluceptate during a two-year period were reviewed to obtain data such as concurrent drug therapy, primary diagnosis, and laboratory values. Adult New Zealand white rabbits were then used for testing the biodistribution of technetium /sup 99m/Tc gluceptate when administered concurrently with possibly interacting drugs identified in the chart review--penicillamine, penicillin G potassium, penicillin V potassium, acetaminophen, and trimethoprim-sulfamethoxazole. Chart review revealed no conclusive patterns of altered biodistribution associated with other factors. The data did suggest the possibility that the five drugs listed above might cause increased hepatobiliary clearance of the radiopharmaceutical. Animal tests showed that i.v. penicillamine caused substantial distribution of radioactivity into the gallbladder and small bowel. Minimally increased gallbladder radioactivity occurred when oral acetaminophen and trimethoprim-sulfamethoxazole were administered concurrently. Oral and i.v. penicillins did not increase gallbladder activity. Penicillamine may cause substantial alteration of the biodistribution of technetium /sup 99m/Tc gluceptate

  10. Biodistribution and pharmacokinetic of 1E10 monoclonal antibody after subcutaneous administration in healthy mice

    International Nuclear Information System (INIS)

    León, M; Hernández, I; Aldana, L; Ayra, F; Castro, Y; Leyva, R; García, L; Casaco, A

    2016-01-01

    To evaluate biodistribution and pharmacokinetic of the 1E10, the molecule was radio labelled with 125I and incorporated into a cold antibody formulation. Isotopic labeling was carried out by means of standardized methods.Introduction:1E10 monoclonal antibody was developed at Centre of Molecular Immunology (CIM) as antitumoral drug with proved efficacy in experimental models. In the present investigation, biodistribution and pharmacokinetic studies were conducted with the help of radio isotopic labeling. Materials and methods: 1E10 was supplied by CIM and labeled with 125I by the iodogen method. To male Balb/c mice from CENPALAB a single subcutaneous administration of 1 mg/kg was performed in the supra scapular region and accommodated in metabolic cages during experiments. Blood samples were taken alternating five groups of three animals according with a sparse data design. Biodistribution was carried out by direct organ sampling and radioactive counting. Pharmacokinetic was performed by compartmental analysis. Urine and faces were collected at regular time intervals. Results: Observed pharmacokinetic behaviour is typical of an immunoglobulin in the assay system used, showing a slow clearance and a small volume of distribution. Biodistribution shows no preference for any sampled organs or tissues. Only a high relative uptake was observed in axillary and brachial lymph nodes close to administration site. (author)

  11. Biodistribution and radiation dosimetry of the 18 kDa translocator protein (TSPO) radioligand [{sup 18}F]FEDAA1106: a human whole-body PET study

    Energy Technology Data Exchange (ETDEWEB)

    Takano, Akihiro; Gulyas, Balazs; Varrone, Andrea; Karlsson, Per; Sjoholm, Nils; Halldin, Christer [Karolinska Institutet, Department of Clinical Neuroscience, Psychiatry Section, Stockholm (Sweden); Larsson, Stig; Jonsson, Cathrine; Odh, Richard [Karolinska Institutet, Department of Nuclear Medicine, Stockholm (Sweden); Sparks, Richard [CDE Dosimetry Services, Inc., Knoxville, TN (United States); Tawil, Nabil Al [Karolinska University Hospital, Karolinska Trial Alliance, Stockholm (Sweden); Hoffmann, Anja; Zimmermann, Torsten; Thiele, Andrea [Bayer Schering Pharma AG, Berlin (Germany)

    2011-11-15

    [{sup 18}F]FEDAA1106 is a recently developed positron emission tomography (PET) radioligand for in vivo quantification of the 18 kDa translocator protein [TSPO or, as earlier called, the peripheral benzodiazepine receptor (PBR)]. TSPO imaging is expected to be useful for the clinical evaluation of neuroinflammatory diseases. The aim of this study was to provide dosimetry estimates for [{sup 18}F]FEDAA1106 based on human whole-body PET measurements. PET scans were performed for a total of 6.6 h after the injection of 183.8 {+-} 9.1 MBq of [{sup 18}F]FEDAA1106 in six healthy subjects. Regions of interest were drawn on coronal images. Estimates of the absorbed doses of radiation were calculated using the OLINDA software. Peak uptake was largest in lungs, followed by liver, small intestine, kidney, spleen and other organs. Peak values of the percent injected dose (%ID) at a time after radioligand injection were calculated for the lungs (27.1%ID at 0.2 h), liver (21.1%ID at 0.6 h), small intestine (10.4%ID at 6.3 h), kidney (4.9%ID at 1.8 h) and spleen (4.6%ID at 0.6 h). The largest absorbed dose was found in the spleen (0.12 mSv/MBq), followed by kidneys (0.094 mSv/MBq). The calculated mean effective dose was 0.036 mSv/MBq. Based on the distribution and dose estimates, the estimated radiation burden of [{sup 18}F]FEDAA1106 is moderately higher than that of [{sup 18}F]fluorodeoxyglucose (FDG). In clinical studies, the administered activity of this radioligand ought to be adjusted in line with regional regulations. This result would be helpful for further clinical TSPO imaging studies. (orig.)

  12. Hepatobiliary delivery of polyaminopolycarboxylate chelates: Synthesis and characterization of a cholic acid conjugate of EDTA and biodistribution and imaging studies with its indium-111 chelate

    Energy Technology Data Exchange (ETDEWEB)

    Betebenner, D.A.; Carney, P.L.; Zimmer, A.M.; Kazikiewicz, J.M.; Bruecher, E.S.; Sherry, A.D.; Johnson, D.K. (Abbott Laboratories, Abbott Park, Illinois (USA))

    1991-03-01

    A conjugate in which the steroid nucleus of cholic acid was linked to EDTA via an 11-atom spacer was obtained by reacting the succinimidyl ester of cholic acid with the amine formed by reaction of a benzyl isothiocyanate derivative of EDTA with N-(tert-butoxycarbonyl)ethylenediamine and subsequent deprotection. Potentiometric titration studies with model complexes showed that the EDTA moiety retained the ability to form 1:1 chelates of high thermodynamic stability, although formation constants were some 3-4 log K units lower for complexes of the conjugate than for the analogous chelates with underivatized EDTA. A complex formed between the cholic acid-EDTA conjugate and 111InIII was clearly rapidly into the liver when injected iv into mice, with subsequent excretion from the liver into the gastrointestinal tract being complete within 1 h of injection. Radioscintigraphic imaging studies conducted in a rabbit given the 111In-labeled conjugate also showed early liver uptake followed by rapid clearance from the liver into the intestine, with good visualization of the gallbladder in images obtained at 20-25 min postinjection. It is concluded that conjugation to cholic acid provides a useful means for the hepatobiliary delivery of EDTA chelates that otherwise exhibit predominantly extracellular distribution and renal clearance.

  13. Hepatobiliary delivery of polyaminopolycarboxylate chelates: Synthesis and characterization of a cholic acid conjugate of EDTA and biodistribution and imaging studies with its indium-111 chelate

    International Nuclear Information System (INIS)

    Betebenner, D.A.; Carney, P.L.; Zimmer, A.M.; Kazikiewicz, J.M.; Bruecher, E.S.; Sherry, A.D.; Johnson, D.K.

    1991-01-01

    A conjugate in which the steroid nucleus of cholic acid was linked to EDTA via an 11-atom spacer was obtained by reacting the succinimidyl ester of cholic acid with the amine formed by reaction of a benzyl isothiocyanate derivative of EDTA with N-(tert-butoxycarbonyl)ethylenediamine and subsequent deprotection. Potentiometric titration studies with model complexes showed that the EDTA moiety retained the ability to form 1:1 chelates of high thermodynamic stability, although formation constants were some 3-4 log K units lower for complexes of the conjugate than for the analogous chelates with underivatized EDTA. A complex formed between the cholic acid-EDTA conjugate and 111InIII was clearly rapidly into the liver when injected iv into mice, with subsequent excretion from the liver into the gastrointestinal tract being complete within 1 h of injection. Radioscintigraphic imaging studies conducted in a rabbit given the 111In-labeled conjugate also showed early liver uptake followed by rapid clearance from the liver into the intestine, with good visualization of the gallbladder in images obtained at 20-25 min postinjection. It is concluded that conjugation to cholic acid provides a useful means for the hepatobiliary delivery of EDTA chelates that otherwise exhibit predominantly extracellular distribution and renal clearance

  14. A phase 1 study of 131I-CLR1404 in patients with relapsed or refractory advanced solid tumors: dosimetry, biodistribution, pharmacokinetics, and safety.

    Directory of Open Access Journals (Sweden)

    Joseph J Grudzinski

    Full Text Available (131I-CLR1404 is a small molecule that combines a tumor-targeting moiety with a therapeutic radioisotope. The primary aim of this phase 1 study was to determine the administered radioactivity expected to deliver 400 mSv to the bone marrow. The secondary aims were to determine the pharmacokinetic (PK and safety profiles of (131I-CLR1404.Eight subjects with refractory or relapsed advanced solid tumors were treated with a single injection of 370 MBq of (131I-CLR1404. Whole body planar nuclear medicine scans were performed at 15-35 minutes, 4-6, 18-24, 48, 72, 144 hours, and 14 days post injection. Optional single photon emission computed tomography imaging was performed on two patients 6 days post injection. Clinical laboratory parameters were evaluated in blood and urine. Plasma PK was evaluated on (127I-CLR1404 mass measurements. To evaluate renal clearance of (131I-CLR1404, urine was collected for 14 days post injection. Absorbed dose estimates for target organs were determined using the RADAR method with OLINDA/EXM software.Single administrations of 370 MBq of (131I-CLR1404 were well tolerated by all subjects. No severe adverse events were reported and no adverse event was dose-limiting. Plasma (127I-CLR1404 concentrations declined in a bi-exponential manner with a mean t½ value of 822 hours. Mean Cmax and AUC(0-t values were 72.2 ng/mL and 15753 ng • hr/mL, respectively. An administered activity of approximately 740 MBq is predicted to deliver 400 mSv to marrow.Preliminary data suggest that (131I-CLR1404 is well tolerated and may have unique potential as an anti-cancer agent.ClinicalTrials.gov NCT00925275.

  15. [11 C]Rhodamine-123: Synthesis and biodistribution in rodents

    International Nuclear Information System (INIS)

    Bao Xiaofeng; Lu Shuiyu; Liow, Jeih-San; Morse, Cheryl L.; Anderson, Kacey B.; Zoghbi, Sami S.; Innis, Robert B.; Pike, Victor W.

    2012-01-01

    Introduction: Rhodamine-123 is a known substrate for the efflux transporter, P-glycoprotein (P-gp). We wished to assess whether rhodamine-123 might serve as a useful substrate for developing probes for imaging efflux transporters in vivo with positron emission tomography (PET). For this purpose, we aimed to label rhodamine-123 with carbon-11 (t 1/2 = 20.4 min) and to study its biodistribution in rodents. Methods: [ 11 C]Rhodamine-123 was prepared by treating rhodamine-110 (desmethyl-rhodamine-123) with [ 11 C]methyl iodide. The biodistribution of this radiotracer was studied with PET in wild-type mice and rats, in efflux transporter knockout mice, in wild-type rats pretreated with DCPQ (an inhibitor of P-gp) or with cimetidine (an inhibitor of organic cation transporters; OCT), and in P-gp knockout mice pretreated with cimetidine. Unchanged radiotracer in forebrain, plasma and peripheral tissues was also measured ex vivo at 30 min after radiotracer administration to wild-type and efflux transporter knockout rodents. Results: [ 11 C]Rhodamine-123 was obtained in 4.4% decay-corrected radiochemical yield from cyclotron-produced [ 11 C]carbon dioxide. After intravenous administration of [ 11 C]rhodamine-123 to wild-type rodents, PET and ex vivo measurements showed radioactivity uptake was very low in brain, but relatively high in some other organs such as heart, and especially liver and kidney. Inhibition of P-gp increased uptake in brain, heart, kidney and liver, but only by up to twofold. Secretion of radioactivity from kidney was markedly reduced by OCT knockout or pretreatment with cimetidine. Conclusions: [ 11 C]Rhodamine-123 was unpromising as a PET probe for P-gp function and appears to be a strong substrate of OCT in kidney. Cimetidine appears effective for blocking OCT in kidney in vivo.

  16. Biodistribution of immunoliposome labeled with Tc-99m in tumor xenografted mice

    International Nuclear Information System (INIS)

    Kitamura, Naoto; Shigematsu, Naoyuki; Nakahara, Tadaki; Kanoh, Momoe; Hashimoto, Jun; Kunieda, Etsuo; Kubo, Atsushi

    2009-01-01

    Immunoliposome (PEG, GAH, liposome; PGL), consisting of F(ab') 2 fragment of monoclonal antibody, GAH and polyethyleneglycol-coated (PEGylated) liposome was provided. Immunoliposome, PGL was labeled with technetium-99m (Tc-99m) by two methods: labeling F(ab') 2 fragment with Tc-99m; Tc-99m-PGL, and entrapping Tc-99m into liposome; PGL[Tc-99m]. The objective of this study was to compare the biodistribution of Tc-99m-PGL and PGL[Tc-99m] in human gastric cancer xenografted mice. Tc-99m-PGL, PGL[Tc-99m], and Tc-99m-entrapped liposome; Lipo[Tc-99m] were prepared. They were injected into human gastric cancer, MKN45, xenografted mice via the tail vein, and their biodistribution was studied. No marked accumulation of either PGL[Tc-99m] or Lipo[Tc-99m] was observed in the stomach. The uptake of Tc-99m-PGL by the liver, spleen, and lung was higher than that by the tumor. On the other hand, the uptake of PGL[Tc-99m] by the lung and spleen was markedly lower as compared with that of Tc-99m-PGL; the accumulation of PGL[Tc-99m] was lower in the lung and higher in the spleen as compared with that of the tumor. Although the liver uptake of PGL[Tc-99m] was markedly decreased as compared with that of Tc-99m-PGL, it was higher than the uptake of the tumor. The Tc-99m-PGL was strongly taken up by the tumor, with a high level of incorporation also seen in the stomach. These findings suggest the need for further study of the labeling stability. PGL[Tc-99m] appears to show promise for high tumor uptake and retention. This is an important implication for the potential application of immunoliposomes entrapped with Re-186, instead of Tc-99m, in internal radiotherapy. (author)

  17. Physics studies in Europe; a comparative study

    NARCIS (Netherlands)

    Steenstrup, S; dalle Rose, LFD; Jones, WG; Tugulea, L; van Steenwijk, FJ

    What are the differences and similarities between physics studies at different universities across Europe (here the definition of Europe is broad)? How much does a student have to work to obtain a degree in physics? Questions like those prompted EUPEN (European Physics Education Network) to make a

  18. Native and Complexed IGF-1: Biodistribution and Pharmacokinetics in Infantile Neuronal Ceroid Lipofuscinosis

    Directory of Open Access Journals (Sweden)

    Tuulia Huhtala

    2012-01-01

    Full Text Available Infantile neuronal ceroid lipofuscinosis (INCL is a severe neurodegenerative disorder of childhood characterized by selective death of cortical neurons. Insulin-like growth factor 1 (IGF-1 is important in embryonic development and is considered as a potential therapeutic agent for several disorders of peripheral and central nervous systems. In circulation IGF-1 is mainly bound to its carrier protein IGFBP-3. As a therapeutic agent IGF-1 has shown to be more active as free than complexed form. However, this may cause side effects during the prolonged treatment. In addition to IGFBP-3 the bioavailability of IGF-1 can be modulated by using mesoporous silicon nanoparticles (NPs which are optimal carriers for sustained release of unstable peptide hormones like IGF-1. In this study we compared biodistribution, pharmacokinetics, and bioavailability of radiolabeled free IGF-1, IGF-1/IGFBP-3, and IGF-1/NP complexes in a Cln1-/- knockout mouse model. IGF-1/NP was mainly accumulated in liver and spleen in all studied time points, whereas minor and more constant amounts were measured in other organs compared to free IGF-1 or IGF-1/IGFBP-3. Also concentration of IGF-1/NP in blood was relatively high and stable during studied time points suggesting continuous release of IGF-1 from the particles.

  19. Effect of iron deficiency anemia on the biodistribution of 99mTc radiopharmaceuticals

    International Nuclear Information System (INIS)

    Calmanovici, Gabriela P.; Salgueiro, Maria J.; Janjetic, Mariana A.; Leonardi, Natalia M.; Boccio, Jose R.; Zubillaga, Marcela B.

    2006-01-01

    The distribution of colloids and labeled cells in organs is influenced by their intrinsic properties and by the state of the investigated subject. Iron deficiency remains an unsolved nutritional problem all over the world; one of its severe consequences is anemia. Because iron metabolism principally takes place in the liver, spleen, bone marrow, skeletal muscle and blood, we studied the effect of iron deficiency anemia on the biodistribution of 99m Tc phytate, 99m Tc gelatin colloid and 99m Tc RBC (red blood cells labeled with 99m Tc). Our results show that iron deficiency anemia modifies the pattern of biodistribution of the two colloids assayed. However, this behavior is different for both of them. This work contributes to studies that kinetically and statistically establish that iron deficiency anemia induces a significant inversion in the spleen-liver activity relationship when centellographic studies are performed with colloids such as 99m Tc phytate

  20. Comparative imaging and biodistribution studies with an anti-CEA monoclonal antibody and its F(ab)2 and Fab fragments in mice with colon carcinoma xenografts

    International Nuclear Information System (INIS)

    Andrew, S.M.; Pimm, M.V.; Baldwin, R.W.; Perkins, A.C.

    1986-01-01

    An IgG1 mouse monoclonal antibody directed against CEA has been digested with papain to yield F(ab) 2 and Fab fragments. Following radioiodination, intact antibody and fragments showed specific binding to cells of a CEA-producing tumour, although the immune reactivities of the fragments were lower than that of intact antibody. Gamma scintigraphy of nude mice bearing CEA producing human tumour xenografts and injected with 131 I-labelled fragments showed earlier and superior imaging of tumours than did 131 I-intact antibody, and this was most marked with the Fab fragment. Sequential dissection analyses showed that this was due to earlier and higher tumour-to-blood ratios with fragments than with intact antibody, but in absolute terms the degree of localization of both fragment types was significantly lower than that of intact antibody. (orig.)

  1. Biodistribution and radiation dosimetry of the α7 nicotinic acetylcholine receptor ligand [11C]CHIBA-1001 in humans

    International Nuclear Information System (INIS)

    Sakata, Muneyuki; Wu, Jin; Toyohara, Jun; Oda, Keiichi; Ishikawa, Masatomo; Ishii, Kenji; Hashimoto, Kenji; Ishiwata, Kiichi

    2011-01-01

    Introduction: 4-[ 11 C]Methylphenyl 2,4-diazabicyclo[3.2.2]nonane-2-carboxylate ([ 11 C]CHIBA-1001) is a newly developed positron emission tomography (PET) ligand for mapping α 7 nicotinic acetylcholine receptors. We investigated whole-body biodistribution and radiation dosimetry of [ 11 C]CHIBA-1001 in humans and compared the results with those obtained in mice. Methods: Dynamic whole-body PET was carried out for three human subjects after administering a bolus injection of [ 11 C]CHIBA-1001. Emission scans were collected in two-dimensional mode over five bed positions. Regions of interest were placed over 12 organs. Radiation dosimetry was estimated from the residence times of these source organs using the OLINDA program. Biodistribution data from mice were also used for the prediction of radiation dosimetry in humans, and results with and those without accommodation of different proportions of organ-to-total-body mass were compared with the results from the human PET study. Results: In humans, the highest accumulation was observed in the liver, whereas in mice, the highest accumulation was observed in the urinary bladder. The estimated effective dose from the human PET study was 6.9 μSv/MBq, and that from mice was much underestimated. Conclusion: Effective dose estimates for [ 11 C]CHIBA-1001 were compatible with those associated with other common nuclear medicine tests. Absorption doses among several organs were considerably different between the human and mouse studies. Human dosimetry studies for the investigation of radiation safety are desirable as one of the first clinical trials of new PET probes before their application in subsequent clinical investigations.

  2. Biodistribution parameters and radiation absorbed dose estimates for radiolabeled human low density lipoprotein

    International Nuclear Information System (INIS)

    Hay, R.V.; Ryan, J.W.; Williams, K.A.; Atcher, R.W.; Brechbiel, M.W.; Gansow, O.A.; Fleming, R.M.; Stark, V.J.; Lathrop, K.A.; Harper, P.V.

    1992-01-01

    The authors propose a model to generate radiation absorbed dose estimates for radiolabeled low density lipoprotein (LDL), based upon eight studies of LDL biodistribution in three adult human subjects. Autologous plasma LDL was labeled with Tc-99m, I-123, or In-111 and injected intravenously. Biodistribution of each LDL derivative was monitored by quantitative analysis of scintigrams and direct counting of excreta and of serial blood samples. Assuming that transhepatic flux accounts for the majority of LDL clearance from the bloodstream, they obtained values of cumulated activity (A) and of mean dose per unit administered activity (D) for each study. In each case highest D values were calculated for liver, with mean doses of 5 rads estimated at injected activities of 27 mCi, 9 mCi, and 0.9 mCi for Tc-99m-LDL, I-123-LDL, and In-111-LDL, respectively

  3. Pharmacokinetics and Biodistribution of the Illegal Food Colorant Rhodamine B in Rats.

    Science.gov (United States)

    Cheng, Yung-Yi; Tsai, Tung-Hu

    2017-02-08

    The International Agency for Research on Cancer (IARC) demonstrated rhodamine B as a potential carcinogen in 1978. Nevertheless, rhodamine B has been illegally used as a colorant in food in many countries. Few pharmacokinetic and toxicological investigations have been performed since the first pharmacokinetic study on rhodamine B in 1961. The aims of this study were to develop a simple and sensitive high-performance liquid chromatography method with fluorescence detection for the quantitative detection of rhodamine B in the plasma and organs of rats and to estimate its pharmacokinetics and biodistribution. The results demonstrated that the oral bioavailabilities of rhodamine B were 28.3 and 9.8% for the low-dose and high-dose exposures, respectively. Furthermore, rhodamine B was highly accumulated in the liver and, to a lesser extent, the kidney, but was undetectable in the brain. These results provide useful information for improving the pharmacokinetics and biodistribution of rhodamine B, supporting additional food safety evaluations.

  4. Fluorescent Labeling and Biodistribution of Latex Nanoparticles Formed by Surfactant-Free RAFT Emulsion Polymerization.

    Science.gov (United States)

    Poon, Cheuk Ka; Tang, Owen; Chen, Xin-Ming; Kim, Byung; Hartlieb, Matthias; Pollock, Carol A; Hawkett, Brian S; Perrier, Sébastien

    2017-10-01

    The authors report the preparation of a novel range of functional polyacrylamide stabilized polystyrene nanoparticles, obtained by surfactant-free reversible addition-fragmentation chain transfer (RAFT) emulsion polymerization, their fluorescent tagging, cellular uptake, and biodistribution. The authors show the versatility of the RAFT emulsion process for the design of functional nanoparticles of well-defined size that can be used as drug delivery vectors. Functionalization with a fluorescent tag offers a useful visualization tool for tracing, localization, and clearance studies of these carriers in biological models. The studies are carried out by labeling the sterically stabilized latex particles chemically with rhodamine B. The fluorescent particles are incubated in a healthy human renal proximal tubular cell line model, and intravenously injected into a mouse model. Cellular localization and biodistribution of these particles on the biological models are explored. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Randomized, interventional, prospective, comparative study to ...

    African Journals Online (AJOL)

    Randomized, interventional, prospective, comparative study to evaluate the antihypertensive efficacy and tolerability of ramipril versus telmisartan in stage 1 hypertensive patients with diabetes mellitus.

  6. Production, quality control, biodistribution assessment and preliminary dose evaluation of {sup 166}Ho-alendronate as a bone marrow ablative agent

    Energy Technology Data Exchange (ETDEWEB)

    Fakhari, Ashraf [Tehran University of Medical Sciences (Iran, Islamic Republic of). Dept. of Radiopharmacy; Jalilian, Amir Reza; Yousefnia, Hassan; Zolghadri, Samaneh; Samani, Ali Bahrami; Akbari, Mahmoud Reza; Deha, Fariba Johari [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of); Shafiee-Ardestani, Mahdi; Khalaj, Ali [Tehran University of Medical Sciences (Iran, Islamic Republic of). Dept. of Medicinal Chemistry

    2015-07-01

    In this study, production, quality control and biodistribution studies of {sup 166}Ho-alendronate have been presented and followed by dosimetric evaluation for human based on biodistribution data in wild-type rats. {sup 166}Ho chloride was obtained by thermal neutron irradiation of natural {sup 165}Ho(NO{sub 3}){sub 3} samples. {sup 166}Ho-alendronate complex was prepared by adding the desired amount of alkaline alendronate solution (0.2 mL, 150 mg/mL) to 3-5 mCi of the {sup 166}HoCl{sub 3} solution. Radiochemical purity of the complex was monitored by instant thin layer chromatography (ITLC). {sup 166}Ho-alendronate complex was prepared in high radiochemical purity (> 99%, ITLC) and specific activity of 4.4 GBq/mmol. Stability studies of the complex in the final preparation and in the presence of human serum were performed up to 48 h. The major accumulation of the radio-complex was in the bone tissues followed by absorbed dose evaluation of each human organ by RADAR software used for modelling the radiation dose delivered. The final preparation was administered to wild-type rats and biodistribution of the complex was performed 2-48 h post injection showing major accumulation of the complex in the bone tissue. The highest absorbed dose for {sup 166}Ho-alendronate is observed in bone surface and red marrow with 2.670 and 1.880 mSv/MBq; respectively. These findings suggest that {sup 166}Ho-alendronate has considerable characteristics compared to {sup 166}Ho-DOTMP and can be a possible candidate for bone marrow ablation in patients with multiple myeloma.

  7. Radiolabeling of codeine with 131I and its biodistribution in rats

    International Nuclear Information System (INIS)

    Enginar, H.

    2009-01-01

    Codeine which was extracted from dry capsules of the opium poppy (Papaver somniferum) was purified by HPLC (High Performance Liquid Chromatography) and characterized by NMR (Nuclear Magnetic Resonance) and IR (Infrared) spectroscopy techniques. The purified compound was labeled with 131 I and biodistribution studies were performed in rats. Radioiodinated codeine distributed uniformly in the cerebellum, m.pons, striatum and hypothalamus while the other branch of brain and Stomach, urinary bladder, and small intestine uptakes were significantly higher than other tissues. (author)

  8. Comparative studies of D2 receptors and cerebral blood flow in hemi-Parkinsonism rats

    International Nuclear Information System (INIS)

    Lin Yansong; Lin Xiangtong

    2000-01-01

    Objective: To study the relationship between dopamine D 2 receptors and cerebral blood flow in hemi-Parkinsonism rats. Methods: Hemi-Parkinsonism rats were made by stereotaxic 6-hydroxy dopamine (6-OH-DA) lesions in substantia nigra and ventral tegmental area, apomorphine (Apo) which could induce the successful model rat to rotate toward the intact side was used to select the rat models, 125 I-IBZM in vivo autoradiography and 99 Tc m -HMPAO regional cerebral biodistribution analysis were used to study D 2 receptors and cerebral blood flow. The HPLC-ECD was used to measure striatum DA and its metabolite content . Results: the lesioned side striatum DA and its metabolites homovanillic acid (HVA) 3,4-dihyroxy-phenylacetic acid (DOPAC) reduced significantly than that of the intact side and pseudo-operated group, striatum/cerebellum 125 I-IBZM uptake ratio was 8.04 +- 0.71 in lesioned side of hemi-Parkinsonism rats, significantly increased compared with the intact side and the pseudo-operated group (P 0.05). Conclusions: the 6-OH-DA lesioned side DA content decreased significantly and thus induced a compensative up-regulation of striatum D 2 receptor binding sites in hemi-Parkinsonism rats, which show good correlation with rotation behavior induced by Apo. Comparing with cerebral blood flow, D 2 receptor reflected by IBZM seems to be more specific and earlier to detect the cerebral functional impairment in experimental hemi-Parkinsonism

  9. Preparation of 177Lu-DTPA-BIS-BIOTIN and biodistribution evaluation in normal mice

    International Nuclear Information System (INIS)

    Deng Xinrong; Luo Zhifu; Du Jin

    2010-01-01

    The labeling method for 177 Lu-DTPA-BIS-BIOTIN was established, and the biodistribution of 177 Lu-DTPA-BIS-BIOTIN in normal mice was carried out as well. Under the optimal experimental condition (DTPA-BIS-BIOTIN 25 μg, pH=4.5 reacting at 80 degree C for 20 min), the labeling yield of 177 Lu-DTPA-BIS-BIOTIN is more than 99.0%. 177 Lu-DTPA-BIS-BIOTIN shows pretty good in vitro stability. The biodistribution of 177 Lu-DTPA-BIS-BIOTIN in normal mice shows a rapid blood clearance. The uptake of 177 Lu-DTPA-BIS-BIOTIN is mainly accumulated in liver, spleen and kidney. 177 Lu-DTPA-BIS-BIOTIN is excreted by kidney. The results provide the basis for further study on 177 Lu-DTPA-BIS-BIOTIN used in pretargeted radioimage and radiotherapy of cancer. (authors)

  10. The biodistribution and kinetics of the 153Sm labelled avidin, streptavidin and biotin

    International Nuclear Information System (INIS)

    Li Guiping; Zhu Chengmo; Jiang Xufeng; Feng Guowei; Zhang Shengguo

    1999-01-01

    Due to the high affinity of biotin to Av or SA. The authors labelled a biotin derivative (DTPA-biotin) with 153 Sm and then bound this 153 Sm labelled DTPA-biotin to Av or SA. The in vivo kinetics and biodistribution of 153 Sm labelled Av, SA and DTPA-biotin were studied in the rat and mice. The results demonstrated that 153 Sm-Av cleared from the blood rapidly with high liver and renal uptake; 153 Sm-SA cleared from blood slowly with high retention in liver, spleen and kidney, whereas 153 Sm metabolize more fast, and excreted mainly through the kidney. Thereby, the biodistribution difference of SA and Av mentioned above provided an experimental basis for the selection of different components of A-V system in pre-targeting radio-immuno imaging and radioimmunotherapy

  11. The biodistribution and effect on hepatic parenchyma with intraarterial injected I-131 lipiodol into hepatic artery

    International Nuclear Information System (INIS)

    Kim, Dong Ik; Suh, Jung Ho; Yoo, Hyung Sik; Lee, Jong Tae; Kim, Ki Whang; Park, Chan Il; Kim, Byung Ro

    1989-01-01

    Iodized oil has been used as a contrast agent in lymphangiography. One of the commercially available compounds is Lipidol Ultra-fluid(LUF) which contains 38% iodine by weight. Nakakuma et al(1979) reported that LUF was selectively retained in the hypervascular hepatocellular carcinoma when injected directly into the ligated hepatic artery. Since that time, it has been widely utilized in the detection as well as the therapeutic attempts of hepatocellular carcinoma, where it has been mixed with chemotherapeutic agents or labeled with radioactive I-131. Like all significant advances, the mechanism of lipid retention within the hepatocellular carcinoma is not clearly understood, and also there is a lack of information about the biodistribution and kinetics of I-131 Lipiodol. The apparent safety of this technique require confirmation. The present study was aimed to assess the biodistribution and kinetics of intraarterially injected I-131 Lipiodol and the histologic changes in canine livers. It was also to verify the safety of this technique in clinical applications. Radioactive iodized oil was obtained by simple exchange method . 518 ± 19 MBq(14 mCi, about 1 mCi/kg body weight) of I-131 Lipiodol was injected intraarterially in 12 dogs as a experimental group. Serial count rates over the livers under gamma camera were measured, and then it was compared with quantitative analysis of radioactivities distributed in liver, lung, spleen, kidney, thyroid, bile and circulating blood using dose calibrator after sacrifice at various time intervals. Cumulative radiation doses were calculated by Quimby method. The effect of I-131 lipiodol on hepatic function were analysed by serial liver function tests after intrahepatic injection of I-131 Lipiodol and compared with preinjection values. Liver tissue obtained after sacrifice were stained with hematoxylin-eosin, Oil red-O, and also election microscopic examinations were performed. The results were summarized as follows; 1

  12. A Potential Dubin-Johnson Syndrome Imaging Agent: Synthesis, Biodistribution, and MicroPET Imaging

    Directory of Open Access Journals (Sweden)

    Jeongsoo Yoo

    2005-01-01

    Full Text Available Dubin-Johnson syndrome (DJS is caused by a deficiency of the human canalicular multispecific organic anion transporter (cMOAT. A new lipophilic copper-64 complex of 1,4,7-tris(carboxymethyl-10-(tetradecyl-1,4,7,10-tetraazadodecane (5 was prepared and evaluated for potential as a diagnostic tool for DJS. The prepared ligand was labeled with 64Cu citrate in high radiochemical purity. In vivo uptake and clearance of the complex was determined through biodistribution studies using normal Sprague-Dawley rats and mutant cMOAT-deficient (TR− rats. In normal rats, the radioactive copper complex was cleared quickly from the body exclusively through the hepatic pathway. The 64Cu complex was taken up rapidly by the liver and quickly excreted into the small intestine and then the upper large intestine, whereas < 1% ID/organ was found in the kidney at all time points post injection. Whereas activity was accumulated continuously in the liver of TR− rats, it was not excreted into the small intestine. MicroPET studies of normal and TR rats were consistent with biodistribution data and showed dramatically different images. This study strongly suggests that cMOAT is involved in excretion of 64Cu-5. The significant difference between the biodistribution data and microPET images of the normal and TR− rats demonstrates that this new 64Cu complex may allow noninvasive diagnosis of DJS in humans.

  13. Pharmacokinetics and biodistribution of a radioiodine labeled peptidomimetic ligand for high-affinity nerve growth factor receptors

    Energy Technology Data Exchange (ETDEWEB)

    Jung, K. H.; Kim, D. H.; Paik, J. Y.; Koh, B. H.; Bae, J. S.; Choe, Y. S.; Lee, K. H.; Kim, B. T. [Samsung Medical Center, Seoul (Korea, Republic of)

    2005-07-01

    Some of the obstacles for the clinical application of whole nerve growth factor (NGF) may be overcome by utilizing small molecule mimetics. We thus investigated the in vivo pharmacokinetics and biodistribution of a small cyclic peptide derived from NGF-[C(92-96)] with high receptor binding affinity. I-125 C(92-96) was labeled with the Bolton-Hunter method, and binding to TrkA/IgG chimeric protein was confirmed on a polyacrylamide gel after cross-linking. Pharmacokinetic analysis was performed in normal ICR mice intravenously injected with 0.5 MBq I-125 C(92-96) containing varying doses of C(92-96). Biodistribution studies were done at 6 h after injection. Cross-linkage analysis confirmed binding of I-125 C(92-96) to the high affinity NGF receptor, TrkA. Intravenously injected I-125 C(92-96) was cleared from the blood in a biexponential manner with an early T1/2{alpha} of 5.2 min and late T1/2{beta} of 121.3 min. Log blood-concentration decreased over time with a k-slope of 0.0025, clearance of 11.8{+-}0.5 ml/min, T1/2 of 4.1{+-}0.4 hr, and volume of distribution of 69.7{+-}4.6 ml. The pattern of elimination from the blood remained essentially unchanged regardless of the dose of added C(92-96), with dose-proportionate increases in AUCs and peak concentrations consistent with linear pharmacokinetics. Biodistribution studies demonstrated high kidney activity suggesting renal excretion of I-125 C(92-96). There were moderate levels of accumulation in the spleen, lungs and liver, followed by the myocardium and skeletal muscle, whereas brain uptake was low (< 0.2 %ID/gm). Intravenously administered C(92-96) follows linear pharmacokinetics, and is cleared from the circulation at a rate comparable to whole NGF despite its substantially smaller size. Although intravenous C(92-96) does not adequately reach brain tissue, clinically relevant doses can achieve major organ accumulation levels that may be sufficient to elicit biologic responses through NGF receptors.

  14. Pharmacokinetics and biodistribution of a radioiodine labeled peptidomimetic ligand for high-affinity nerve growth factor receptors

    International Nuclear Information System (INIS)

    Jung, K. H.; Kim, D. H.; Paik, J. Y.; Koh, B. H.; Bae, J. S.; Choe, Y. S.; Lee, K. H.; Kim, B. T.

    2005-01-01

    Some of the obstacles for the clinical application of whole nerve growth factor (NGF) may be overcome by utilizing small molecule mimetics. We thus investigated the in vivo pharmacokinetics and biodistribution of a small cyclic peptide derived from NGF-[C(92-96)] with high receptor binding affinity. I-125 C(92-96) was labeled with the Bolton-Hunter method, and binding to TrkA/IgG chimeric protein was confirmed on a polyacrylamide gel after cross-linking. Pharmacokinetic analysis was performed in normal ICR mice intravenously injected with 0.5 MBq I-125 C(92-96) containing varying doses of C(92-96). Biodistribution studies were done at 6 h after injection. Cross-linkage analysis confirmed binding of I-125 C(92-96) to the high affinity NGF receptor, TrkA. Intravenously injected I-125 C(92-96) was cleared from the blood in a biexponential manner with an early T1/2α of 5.2 min and late T1/2β of 121.3 min. Log blood-concentration decreased over time with a k-slope of 0.0025, clearance of 11.8±0.5 ml/min, T1/2 of 4.1±0.4 hr, and volume of distribution of 69.7±4.6 ml. The pattern of elimination from the blood remained essentially unchanged regardless of the dose of added C(92-96), with dose-proportionate increases in AUCs and peak concentrations consistent with linear pharmacokinetics. Biodistribution studies demonstrated high kidney activity suggesting renal excretion of I-125 C(92-96). There were moderate levels of accumulation in the spleen, lungs and liver, followed by the myocardium and skeletal muscle, whereas brain uptake was low (< 0.2 %ID/gm). Intravenously administered C(92-96) follows linear pharmacokinetics, and is cleared from the circulation at a rate comparable to whole NGF despite its substantially smaller size. Although intravenous C(92-96) does not adequately reach brain tissue, clinically relevant doses can achieve major organ accumulation levels that may be sufficient to elicit biologic responses through NGF receptors

  15. Streptozotocin (STZ) and schistosomiasis mansoni change the biodistribution of radiopharmaceutical sodium 99mTc-pertechnetate in mice

    International Nuclear Information System (INIS)

    Góes, Vanessa Coelho; Neves, Renata Heisler; Arnóbio, Adriano; Bernardo-Filho, Mario; Machado-Silva, José Roberto

    2016-01-01

    Introduction: Technetium-99m ( 99m Tc) is a radionuclide commonly used in nuclear medicine to obtain 99m Tc-radiopharmaceuticals, which can be used to evaluate either physiological processes or changes related to diseases. It is also used in some experimental studies. Streptozotocin (STZ) administration to rodents causes lesions in very early stages and induces severe and permanent diabetes. Most morbidity of schistosomiasis mansoni is attributed to a granulomatous inflammatory response and associated liver fibrosis. This study was designed to investigate whether STZ administration and schistosomiasis modify the biodistribution of the radiopharmaceutical sodium 99m Tc-pertechnetate. Methods: Adult female mice were infected by exposure to 100 Schistosoma mansoni cercariae (BH strain, Belo Horizonte, Brazil) and euthanized after nine weeks. STZ was administered by a single intraperitoneal injection of 100 mg/kg body weight, 3 or 15 days before euthanasia. Each animal received 100 μl of sodium (Na) 99m Tc-pertechnetate ( 99m TcO 4 − ) (740 kBq). The animals were divided into four groups: A, uninfected; B, infected; C, uninfected + STZ; and D, infected + STZ. Blood, brain, thyroid, heart, lungs, liver, spleen, pancreas and kidneys were removed. The radioactivity was counted and the percentage of the injected dose of Na 99m TcO 4 per gram of the organ (% ID/g) was determined. Results: Three days after the STZ injection, there was a decrease of Na 99m TcO 4 uptake by the liver, lungs, pancreas and kidneys (p < 0.05) in group D when compared with group A. After 15 days, the decrease of Na 99m TcO 4 uptake occurred also in the brain, thyroid, heart, spleen and blood (p < 0.05) in group D. Conclusion: We demonstrated modifications on the biodistribution of Na 99m TcO 4 due to STZ administration and schistosomiasis, possibly due to physiological alterations in some organs. Advances in Knowledge and Implications for Patient Care: The biodistribution of radiopharmaceutical

  16. The rabbit biodistribution of a therapeutic dose of zoledronic acid labeled with Tc-99m

    International Nuclear Information System (INIS)

    Asikoglu, Makbule; Gamze Durak, Funda

    2009-01-01

    The aim of the present study was to label a therapeutic dose of zoledronic acid (ZOL) with Tc-99m, evaluate its in vitro stability and compare its biodistribution to 99m Tc-methylene biphosphonate ( 99m Tc-MDP) in normal rabbits. Preparation of 0.50 mg of 99m Tc-ZOL was carried out by the reduction of 99m Tc-pertechnetate in the presence of stannous chloride. The radiolabeling efficiency was found to be greater than 99%. The labeled complex was stable at least up to 6 h at room temperature determined by paper chromatography. 99m Tc-ZOL and 99m Tc-MDP were administered intravenously to the rabbits for scintigraphic studies. Between 99m Tc-ZOL and 99m Tc-MDP, there were no significant differences in the ratios of femur/BG and lumbar vertebrae/BG, whereas epiphysis/BG and the kidney/BG ratios of 99m Tc-MDP were higher than 99m Tc-ZOL at the static studies.

  17. Biodistribution And Preclinical Test Of P-32 Glass Microspheres For Cancer Therapy

    International Nuclear Information System (INIS)

    A, Laksmi; C, Djoharly; P, Ratlan; W, Widyastuti; Purwoko; Bagiwati, Sri; Setiyowati, Sri; Abidin; Sri, Aguswarini

    2003-01-01

    The superiority of radiopharmaceutical compare to the other techniques of medical services, especially for diagnosis and therapy of several deadly diseases such as cancer, shows that this technique is more specific and accurate. P-32-Glass microsphere (P-32 GMS) is one of the radiopharmaceuticals developed recently for therapy using internal radiation method for several malignant cancers, such as hepatic cancer. The P-32 GMS was prepared by irradiating P-31 GMS with neutron at a nuclear reactor, then the preparation was injected to the cancerous infected area. To make easy injection, it needs suspension agent that was including PVP, dextrose and saline with a composition of 16% PVP - 50% dextrose - saline as 2 : 3 : 3 (v/v/v). As microsphere size should be maintained at 40-60 μm, the injection needle was selected properly in order to remain the particle size of P-32 GMS unchanged when the friction occurs between microspheres and the inside surfaces of the needle. The injection needle used was needle produced by BD with a typical size of 20 G1 Tw. Biodistribution studies were carried out after 1, 3, 5 and 24 hour of injection. Experimental results for 1, 3 and 24 hour post-injection studies showed that 100% activity of P-32 GMS was accumulated at the injected area. For 5 hour post-injection study, accumulation of P-32 GMS activity was also found at stomach besides the injected area, but it was presumed as working error

  18. Biodistribution of {sup 99m} technetium labeled creatinine in healthy rats

    Energy Technology Data Exchange (ETDEWEB)

    Yilmaz, O. [Dokuz Eylul University, Narlidere, Izmir (Turkey). Medical Faculty. Dept. of Animal Research Center; Soylu, A.; Kavukcu, S. [Dokuz Eylul University, Narlidere, Izmir (Turkey). Medical Faculty. Dept. of Pediatrics; Lambrecht, F. Yurt; Durkan, K. [Ege University, Bornova, Izmir (Turkey). Institute of Nuclear Sciences. Dept. of Nuclear Applications]. E-mail: s.kavukcu@deu.edu.tr

    2007-06-15

    The distribution of creatinine, one of the toxic guanidine compounds, in various tissues has not been studied in detail by using radiolabeled creatinine. Our objective was to investigate the biodistribution of creatinine labeled with {sup 99m}technetium ({sup 99m} Tc) by the stannous (II) chloride method in healthy male Wistar rats. Quality controls were carried out by radio thin layer chromatography, high-performance liquid chromatography, and paper electrophoresis. The labeling yield was 85 {+-} 2% under optimum conditions (pH 7 and 100 {mu}g stannous chloride). Rats (N 12) were injected intravenously with {sup 99m} Tc creatinine and their blood and visceral organs were evaluated for {sup 99m} Tc-creatinine uptake as percent of the injected dose per gram wet weight of each tissue (%ID/g). The lowest amount of uptake was detected in the brain and testis. When the rate of uptake was evaluated, only the kidney showed increasing rates of uptake of {sup 99m} Tc-creatinine throughout the study. Kidneys showed the highest amount of uptake throughout the study (P < 0.001 compared to all other organs), followed by liver, spleen and lung tissue. (author)

  19. Samarium oxide as a radiotracer to evaluate the in vivo biodistribution of PLGA nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Mandiwana, Vusani, E-mail: VMandiwana@csir.co.za; Kalombo, Lonji, E-mail: LKalombo@csir.co.za [Centre of Polymers and Composites, CSIR (South Africa); Venter, Kobus, E-mail: Kobus.Venter@mrc.ac.za [South African Medical Research Council (South Africa); Sathekge, Mike, E-mail: Mike.Sathekge@up.ac.za [University of Pretoria and Steve Biko Academic Hospital, Department of Nuclear Medicine (South Africa); Grobler, Anne, E-mail: Anne.Grobler@nwu.ac.za; Zeevaart, Jan Rijn, E-mail: zeevaart@necsa.co.za [North-West University, DST/NWU Preclinical Drug Development Platform (South Africa)

    2015-09-15

    Developing nanoparticulate delivery systems that will allow easy movement and localization of a drug to the target tissue and provide more controlled release of the drug in vivo is a challenge in nanomedicine. The aim of this study was to evaluate the biodistribution of poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles containing samarium-153 oxide ([{sup 153}Sm]Sm{sub 2}O{sub 3}) in vivo to prove that orally administered nanoparticles alter the biodistribution of a drug. These were then activated in a nuclear reactor to produce radioactive {sup 153}Sm-loaded-PLGA nanoparticles. The nanoparticles were characterized for size, zeta potential, and morphology. The nanoparticles were orally and intravenously (IV) administered to rats in order to trace their uptake through imaging and biodistribution studies. The {sup 153}Sm-loaded-PLGA nanoparticles had an average size of 281 ± 6.3 nm and a PDI average of 0.22. The zeta potential ranged between 5 and 20 mV. The [{sup 153}Sm]Sm{sub 2}O{sub 3} loaded PLGA nanoparticles, orally administered were distributed to most organs at low levels, indicating that there was absorption of nanoparticles. While the IV injected [{sup 153}Sm]Sm{sub 2}O{sub 3}-loaded PLGA nanoparticles exhibited the highest localization of nanoparticles in the spleen (8.63 %ID/g) and liver (3.07 %ID/g), confirming that nanoparticles are rapidly removed from the blood by the RES, leading to rapid uptake in the liver and spleen. From the biodistribution data obtained, it is clear that polymeric nanoscale delivery systems would be suitable for improving permeability and thus the bioavailability of therapeutic compounds.

  20. TISCON, a BASIC computer program for the calculation of the biodistribution of radionuclide-labelled drugs in rats and mice

    International Nuclear Information System (INIS)

    Maddalena, D.J.

    1983-09-01

    Animal biodistribution studies on radionuclide-labelled drugs are labour-intensive and time-consuming. A method for rapidly carrying out these studies on rats and mice is presented. An interactive computer program, written in BASIC, is used to calculate parameters of interest, such as per cent injected dose (%ID),%ID per gram and target to non-target ratios

  1. The effect of the administration of iron on Ga-67 uptake in animal tumor and biodistribution

    International Nuclear Information System (INIS)

    Furukawa, Keiji

    1983-01-01

    In 1979 Larson reported that the uptake of Ga-67 in tumor cell was preceded by binding of the Ga-67 to transferrin. Since that time there have been many papers concerning changes in Ga-67 accumulation in experimental tumor by administration of iron before and after Ga-67 injection. This study was undertaken in the attempt to discern what changes are produced in Ga-67 images of tumor-bearing rabbits (VX-II) when iron was administered before and after Ga-67 injection. Additionally, the relationships between the change in the serum iron concentration in the tumor tissue in mice bearing Ehrlich's ascites tumor were studied. The following results were obtained. 1) The tumor uptake and biodistribution of Ga-67 following administration of iron in the form of Fesin (saccharated ferric oxide) or ferric-citrate is obviously diminished. This iron administration leads to an elevated excretion of Ga-67 from tumor and other organs except from bone. From this results, it was found that Ga-67 binds somewhat less avidity than iron to various iron transport protein. Accordingly, Ga-67 biodistribution may be markedly influenced by iron-loading. 2) The Ga-67 activity in blood following administration of iron was noted to suddenly markedly decrease. However, 24-48 hours after iron injection the Ga-67 activity in blood gradually increased. This result suggests that the Ga-67 displaced into the extravascular space by iron-loading reentered the vascular space when the iron concentration of serum returned to normal. 3) The accumulation of Ga-67 in the tumor and soft tissues was slightly decreased compared with controls after iron administration. However, the tumor to blood ratio (T/B) of Ga-67 in mice by iron loading was several time greater than that of Ga-67 alone because the clearance of Ga-67 from the blood was more accelated than that of tumor. The large tumor to blood ratio (T/B) would be advantageous in obtaining a more distinct tumor scan. (author)

  2. Platelet binding and biodistribution of [99mTc]rBitistatin in animal species and humans

    International Nuclear Information System (INIS)

    Knight, Linda C.; Romano, Jan E.; Bright, Lewis T.; Agelan, Alexis; Kantor, Steven; Maurer, Alan H.

    2007-01-01

    Introduction: 99m Tc recombinant bitistatin (rBitistatin) is a radioligand for α IIb β 3 (glycoproteins IIb/IIIa) receptor on platelets and is being developed as a diagnostic radiopharmaceutical for in vivo imaging of acute thrombi and emboli. Prior to the first administration of [ 99m Tc]rBitistatin to human subjects, its biodistribution and effects on platelets were evaluated in animals. This paper reports findings in animal studies in comparison with initial findings in normal human subjects. Methods: [ 99m Tc]rBitistatin was administered to mice, guinea pigs and dogs to assess time-dependent organ distribution, urinary excretion and blood disappearance rates. Blood samples were analyzed to determine radioligand binding to circulating platelets and the extent of plasma protein binding. The effect of [ 99m Tc]rBitistatin on circulating platelet count was determined. These factors were also determined in normal human subjects who received [ 99m Tc]rBitistatin as part of a Phase I clinical trial. Results: The main organs that accumulated [ 99m Tc]rBitistatin were kidneys, liver and spleen in all animal species and humans. The main organs seen on human images were the kidneys and spleen. Liver uptake was fainter, and soft-tissue background was low. [ 99m Tc]rBitistatin bound to circulating platelets in blood, with a higher percentage of binding to platelets in guinea pigs and dogs compared to that in humans. Plasma protein binding was low and of little consequence in view of platelet binding. The main route of excretion was through the urine. [ 99m Tc]rBitistatin did not affect platelet counts in humans or dogs. Conclusions: [ 99m Tc]rBitistatin, when administered at low doses for imaging, has no adverse effects on platelets and has the qualitative biodistribution predicted by animal studies. [ 99m Tc]rBitistatin was found to bind to circulating platelets in humans, suggesting that it will be able to bind to activated platelets in vivo in patients with acute

  3. Radiolabeling of anti-human prostatic specific membrane antigen antibody with 99Tcm and its biodistribution in nude mice bearing human prostate cancer

    International Nuclear Information System (INIS)

    Tu Shaohua; Shen Jiangfan; Tao Rong; Ji Xiaowen; Wang Yancheng

    2012-01-01

    Objective: To study the binding affinity of 99 Tc m labeled anti-human prostatic specific membrane antigen (PSMA) monoclonal antibody (McAb) J591 to prostate cancer cells and the biodistribution of 99 Tc m -J591 in nude mice bearing human prostate cancer. Methods: The McAb J591 was labeled with vTcm by improved Schwarz method and the labeled McAb was purified by Sephadex G-50. The binding affinity of J591 with prostate cancer cells was measured by Flow Cytometry. The nude mice bearing PSMA-positive C4-2 prostate carcinoma xenografts were served as experiment groups, mice with PSMA-negative pc3 tumors served as controls. The biodistribution of 99 Tc m -J591 were carried out in both model nude mice. Results: The radiolabeling efficiency of 99 Tc m -J591 was 78.9±6.2%, and radiochemical purity was more than 90% after purification. The 99 Tc m -J591 showed a good combination with PSMA-positive C4-2 cells and no combination with PSMA-negative PC3 cells in vitro. The biodistribution results showed that 99 Tcm-J591 was accumulated in tumor tissue during the 2-24 hours after injection in experiment groups, and no significant uptake in control group. The uptake of 99 Tcm-J591 in tumor tissue reached a maximum 15.91±5.16 % ID/g in experimental group at 12h post-injection. There was a significant difference compared with controls (P 0.05). Conclusion: The monoclonal antibody J591 exhibits an excellent immuno-reactivity and tumor targeting property, and it may be used in diagnosis and target therapy of prostate cancer. (authors)

  4. Comparative studies of D2 receptors and brain perfusion in hemi-parkinsonism rats

    International Nuclear Information System (INIS)

    Lin Yansong; Lin Xiangtong

    2000-01-01

    The relationship between dopamine D 2 receptors and brain perfusion in hemi-parkinsonism rats was studied. Hemi-parkinsonism rats were made by stereotaxic 6-hydroxy dopamine (6-OH-DA) lesions in substantia nigra (SN) and ventral tegmental area (VTA), apomorphine (Apo) which could induced the successful model rat rotates toward the intact side was used to select the rats, 125 I-IBZM ex-vivo autoradiography analysis and 99m Tc-HM-PAO regional cerebral biodistribution were used to evaluate D 2 receptors and cerebral blood flow. The HPLC-ECD were used to measure striatum DA and its metabolites content. The lesioned side striatum DA and its metabolites HVA DOPAC reduced significantly than that of the intact side and pseudo-operated group, striatum/cerebellum 125 I-IBZM uptake ratio was 8.04 +- 0.71 in lesioned side of hemi-parkinsonism rats, significantly increased compared with the intact side and the pseudo-operated group (p 0.05). These results indicated that in the 6-OH-DA lesioned side DA content decreased significantly and an up-regulation of striatum D 2 receptor binding sites was induced in hemi-parkinsonism rats, which showed good correlation with rotation behavior induced by Apo. Comparing with cerebral blood flow, D 2 receptor reflected by IBZM seems to be more specific and earlier to detect the cerebral functional impairment in experimental hemi-parkinsonism

  5. Lactoferrin-modified rotigotine nanoparticles for enhanced nose-to-brain delivery: LESA-MS/MS-based drug biodistribution, pharmacodynamics, and neuroprotective effects

    Directory of Open Access Journals (Sweden)

    Yan X

    2018-01-01

    Full Text Available Xiuju Yan,1,* Lixiao Xu,1,* Chenchen Bi,1 Dongyu Duan,1 Liuxiang Chu,1 Xin Yu,1 Zimei Wu,1 Aiping Wang,1,2 Kaoxiang Sun1,2 1School of Pharmacy, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University, Ministry of Education, Yantai University, Yantai, Shandong Province, 2State Key Laboratory of Long-Acting and Targeting Drug Delivery System, Shandong Luye Pharmaceutical Co., Ltd, Yantai, Shandong Province, People’s Republic of China *These authors contributed equally to this work Introduction: Efficient delivery of rotigotine into the brain is crucial for obtaining maximum therapeutic efficacy for Parkinson’s disease (PD. Therefore, in the present study, we prepared lactoferrin-modified rotigotine nanoparticles (Lf-R-NPs and studied their biodistribution, pharmacodynamics, and neuroprotective effects following nose-to-brain delivery in the rat 6-hydroxydopamine model of PD.Materials and methods: The biodistribution of rotigotine nanoparticles (R-NPs and Lf-R-NPs after intranasal administration was assessed by liquid extraction surface analysis coupled with tandem mass spectrometry. Contralateral rotations were quantified to evaluate pharmacodynamics. Tyrosine hydroxylase and dopamine transporter immunohistochemistry were performed to compare the neuroprotective effects of levodopa, R-NPs, and Lf-R-NPs.Results: Liquid extraction surface analysis coupled with tandem mass spectrometry analysis, used to examine rotigotine biodistribution, showed that Lf-R-NPs more efficiently supplied rotigotine to the brain (with a greater sustained amount of the drug delivered to this organ, and with more effective targeting to the striatum than R-NPs. The pharmacodynamic study revealed a significant difference (P<0.05 in contralateral rotations between rats treated with Lf-R-NPs and those treated with R-NPs. Furthermore, Lf

  6. New surface radiolabeling schemes of super paramagnetic iron oxide nanoparticles (SPIONs) for biodistribution studies†

    Science.gov (United States)

    Nallathamby, Prakash D.; Mortensen, Ninell P.; Palko, Heather A.; Malfatti, Mike; Smith, Catherine; Sonnett, James; Doktycz, Mitchel J.; Gu, Baohua; Roeder, Ryan K.; Wang, Wei; Retterer, Scott T.

    2016-01-01

    Nanomaterial based drug delivery systems allow for the independent tuning of the surface chemical and physical properties that affect their biodistribution in vivo and the therapeutic payloads that they are intended to deliver. Additionally, the added therapeutic and diagnostic value of their inherent material properties often provides extra functionality. Iron based nanomaterials with their magnetic properties and easily tailorable surface chemistry are of particular interest as model systems. In this study the core radius of the iron oxide nanoparticles (NPs) was 14.08 ± 3.92 nm while the hydrodynamic radius of the NPs, as determined by Dynamic Light Scattering (DLS), was between 90–110 nm. In this study, different approaches were explored to create radiolabeled NPs that are stable in solution. The NPs were functionalized with polycarboxylate or polyamine surface functional groups. Polycarboxylate functionalized NPs had a zeta potential of –35 mV and polyamine functionalized NPs had a zeta potential of +40 mV. The polycarboxylate functionalized NPs were chosen for in vivo biodistribution studies and hence were radiolabeled with 14C, with a final activity of 0.097 nCi mg–1 of NPs. In chronic studies, the biodistribution profile is tracked using low-level radiolabeled proxies of the nanoparticles of interest. Conventionally, these radiolabeled proxies are chemically similar but not chemically identical to the non-radiolabeled NPs of interest. This study is novel as different approaches were explored to create radiolabeled NPs that are stable, possess a hydrodynamic radius of <100 nm and most importantly they exhibit an identical surface chemical functionality as their non-radiolabeled counterparts. Identical chemical functionality of the radiolabeled probes to the non-radiolabeled probes was an important consideration to generate statistically similar biodistribution data sets using multiple imaging and detection techniques. The radiolabeling approach

  7. COMPARATIVE STUDY ON SPECIFIC AND EARLY DETECTION ...

    African Journals Online (AJOL)

    The objective of this study was to compare the sensitivity and specificity of smear and culture methods with rapid serological EIA myco kits manufactured by Omega diagnostics, for the early detection of Mycobacterium tuberculosis (MTB) complex. Sera from various categories of smear and culture results were compared ...

  8. Biodistribution and Lymphatic Tracking of the Main Neurotoxin of Micrurus fulvius Venom by Molecular Imaging

    Directory of Open Access Journals (Sweden)

    Irene Vergara

    2016-03-01

    Full Text Available The venom of the Eastern coral snake Micrurus fulvius can cause respiratory paralysis in the bitten patient, which is attributable to β-neurotoxins (β-NTx. The aim of this work was to study the biodistribution and lymphatic tracking by molecular imaging of the main β-NTx of M. fulvius venom. β-NTx was bioconjugated with the chelator diethylenetriaminepenta-acetic acid (DTPA and radiolabeled with the radionuclide Gallium-67. Radiolabeling efficiency was 60%–78%; radiochemical purity ≥92%; and stability at 48 h ≥ 85%. The median lethal dose (LD50 and PLA2 activity of bioconjugated β-NTx decreased 3 and 2.5 times, respectively, in comparison with native β-NTx. The immune recognition by polyclonal antibodies decreased 10 times. Biodistribution of β-NTx-DTPA-67Ga in rats showed increased uptake in popliteal, lumbar nodes and kidneys that was not observed with 67Ga-free. Accumulation in organs at 24 h was less than 1%, except for kidneys, where the average was 3.7%. The inoculation site works as a depot, since 10% of the initial dose of β-NTx-DTPA-67Ga remains there for up to 48 h. This work clearly demonstrates the lymphatic system participation in the biodistribution of β-NTx-DTPA-67Ga. Our approach could be applied to analyze the role of the lymphatic system in snakebite for a better understanding of envenoming.

  9. Biodistribution of the radiopharmaceutical technetium-99m-sodium phytate in rats after splenectomy

    International Nuclear Information System (INIS)

    Pereira, Kercia Regina Santos Gomes; Acucena, Maria Kadja Meneses Torres; Villarim Neto, Arthur; Rego, Amalia Cinthia Meneses; Bernardo-Filho, Mario; Azevedo, Italo Medeiros; Araujo Filho, Irami; Medeiros, Aldo Cunha

    2008-01-01

    Drugs and surgery can interfere with the biodistribution of radiopharmaceuticals and data about the effect of splenectomy on the metabolism of phytate-Tc-99m are scarce. This study aimed at evaluating the interference of splenectomy on phytate-Tc-99m biodistribution and liver function in rats. The SP group rats (n=6) underwent splenectomy. In group C (control) the animals were not operated on. After 15 days, all rats were injected with 0.1 mL of Tc-99m-phytate via orbital plexus (0.66 MBq). After 30 minutes, liver samples were harvested, weighed and the percentage of radioactivity per gram (%ATI/g) was determined by a Wizard Perkin-Elme gamma counter. The ATI%/g in splenectomized rats (0.99±0.02) was significantly higher than in controls (0.4±0.02), (p=0.034). ALT, AST and HDL were significantly lower in SP rats (p= 0.001) and leucocytosis was observed in SP rats. In conclusion, splenectomy in rats changed the hepatic biodistribution of Tc-99m-phytate and liver enzymatic activity. (author)

  10. Biodistribution of the radiopharmaceutical technetium-99m-sodium phytate in rats after splenectomy

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Kercia Regina Santos Gomes; Acucena, Maria Kadja Meneses Torres; Villarim Neto, Arthur; Rego, Amalia Cinthia Meneses [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Centro de Ciencias da Saude; Bernardo-Filho, Mario [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes. Dept. de Biofisica e Biometria; Azevedo, Italo Medeiros; Araujo Filho, Irami; Medeiros, Aldo Cunha [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Dept. de Cirurgia]. E-mail: aldo@ufrnet.br

    2008-12-15

    Drugs and surgery can interfere with the biodistribution of radiopharmaceuticals and data about the effect of splenectomy on the metabolism of phytate-Tc-99m are scarce. This study aimed at evaluating the interference of splenectomy on phytate-Tc-99m biodistribution and liver function in rats. The SP group rats (n=6) underwent splenectomy. In group C (control) the animals were not operated on. After 15 days, all rats were injected with 0.1 mL of Tc-99m-phytate via orbital plexus (0.66 MBq). After 30 minutes, liver samples were harvested, weighed and the percentage of radioactivity per gram (%ATI/g) was determined by a Wizard Perkin-Elme gamma counter. The ATI%/g in splenectomized rats (0.99{+-}0.02) was significantly higher than in controls (0.4{+-}0.02), (p=0.034). ALT, AST and HDL were significantly lower in SP rats (p= 0.001) and leucocytosis was observed in SP rats. In conclusion, splenectomy in rats changed the hepatic biodistribution of Tc-99m-phytate and liver enzymatic activity. (author)

  11. Effects of broccoli extract on biodistribution and labeling blood components with {sup 99m}Tc-GH

    Energy Technology Data Exchange (ETDEWEB)

    Cekic, Betul; Muftuler, Fazilet Zumrut Biber; Kilcar, Ayfer Yurt; Ichedef, Cigdem; Unak, Perihan [Ege University, Izmir (Turkey). Inst. of Nuclear Sciences. Dept. of Nuclear Applications

    2011-09-15

    Purpose: people consume vegetables without the knowledge of the side effects of the biological and chemical contents and interactions between radiopharmaceuticals and herbal extract. To this end, current study is focused on the effects of broccoli extract on biodistribution of radiolabeled glucoheptonate ({sup 99m}Tc-GH) and radiolabeling of blood components. Methods: GH was labeled with {sup 99m}Tc. Quality control studies were done utilizing TLC method. Biodistribution studies were performed on male rats which were treated via gavage with either broccoli extract or SF as control group for 15 days. Blood samples were withdrawn from rats' heart. Radiolabeling of blood constituents performed incubating with GH, SnCl{sub 2} and {sup 99m} Tc. Results: radiochemical yield of {sup 99m}Tc-GH is 98.46{+-}1.48 % (n=8). Biodistribution studies have shown that according to the control, the treated group with broccoli has approximately 10 times less uptake in kidney. The percentage of the radioactivity ratios of the blood components is found to be same in both groups. Conclusions: although there is no considerable effect on the radiolabeling of blood components, there is an outstanding change on the biodistribution studies especially on kidneys. The knowledge of this change on kidney uptake may contribute to reduce the risk of misdiagnosis and/or repetition of the examinations in Nuclear Medicine. (author)

  12. Biodistribution dosimetric study of radiopharmaceutical {sup 99mT}c Ixolaris in mice for melanoma diagnosis by molecular image and translational model for human beings; Estudo dosimetrico da biodistribuicao do radiofarmaco Ixolaris-{sup 99m}Tc em camundongos para diagnostico de melanoma atraves de imagem molecular e modelo translacional para humanos

    Energy Technology Data Exchange (ETDEWEB)

    Soriano, Sarah Canuto Silva

    2015-07-01

    The labeling of Ixolaris with {sup 99m}Tc was developed by Barboza et.al. (2013) aiming its use primarily in glioblastoma and after in melanoma diagnosis, a less common but very aggressive cancer and with high mortality rate. Preliminary tests on animals have proven its effectiveness of labeling but a dosimetric study to human clinical trials should be performed. This study aimed to: (1) determine the biokinetic model for the radiotracer {sup 99m}Tc-Ixolaris in mice by imaging dosimetry method; and (2) estimate the absorbed and effective dose resulting from the use of a new radiopharmaceutical for melanoma and metastases diagnosis in human beings, since a dosimetric study of new radiopharmaceuticals in animals is necessary to test them subsequently in humans and apply for registration in ANVISA. According to SPECT images, was found a latency period of 15 to 21 days for the development of lung metastasis in mice. Three C57BL6 mice, one control animal, and two animals with induced cell line B16-F10 murine melanoma were tested. The {sup 99m}Tc-Ixolaris radiopharmaceutical was administered intravenously in a caudal vein, and SPECT images were acquired 0.5 h, 1.5 h, 2.5 h, 3.5 h and 24 h post-administration for analysis and biodistribution quantification. The biokinetic model was determined and thus, obtained cumulative activity in order to estimate the absorbed dose in each organ. The mass and metabolic differences between mice and humans were considered and used to extrapolate the data acquired at different scales. Based on dose factors provided by the software MIRDOSE and Olinda (S factor), absorbed doses in irradiated target organs were calculated for the source organs, and finally the effective dose was estimated. The results indicate that for diagnostic exams conducted in human melanoma patients by administering approximately 25.7 MBq the estimated effective dose was 4.3 mSv. Comparing with effective doses obtained in other diagnostic techniques with {sup 99m

  13. Toxicity and biodistribution of orally administered casein nanoparticles.

    Science.gov (United States)

    Gil, Ana Gloria; Irache, Juan Manuel; Peñuelas, Iván; González Navarro, Carlos Javier; López de Cerain, Adela

    2017-08-01

    In the last years, casein nanoparticles have been proposed as carriers for the oral delivery of biologically active compounds. However, till now, no information about their possible specific hazards in vivo was available. The aim of this work was to assess the safety of casein nanoparticles when administered orally to animals through a 90 days dose-repeated toxicity study (OECD guideline 408), that was performed in Wistar rats under GLP conditions. After 90 days, no evidences of significant alterations in animals treated daily with 50, 150 or 500 mg/kg bw of nanoparticles were found. This safety agrees well with the fact that nanoparticles were not absorbed and remained within the gut as observed by radiolabelling in the biodistribution study. After 28 days, there was a generalized hyperchloremia in males and females treated with the highest dose of 500 mg/kg bw, that was coupled with hypernatremia in the females. These effects were related to the presence of mannitol which was used as excipient in the formulation of casein nanoparticles. According to these results, the No Observed Adverse Effect Level (NOAEL) could be established in 150 mg/kg bw/day and the Lowest Observed Effect Level (LOEL) could be established in 500 mg/kg bw/day. Copyright © 2017. Published by Elsevier Ltd.

  14. In vivo biodistribution of stable spherical and filamentous micelles probed by high-sensitivity SPECT

    NARCIS (Netherlands)

    Jennings, L.; Ivashchenko, O.; Marsman, I. J C; Laan, A.C.; Denkova, A.G.; Waton, g; Beekman, F.J.; Schosseler, F.; Mendes, E.

    2016-01-01

    Understanding how nanoparticle properties such as size, morphology and rigidity influence their circulation time and biodistribution is essential for the development of nanomedicine therapies. Herein we assess the influence of morphology on cellular internalization, in vivo biodistribution and

  15. Biodistribution of the 18F-labelled advanced glycation end products Nε-carboxymethyllysine (CML) and Nε-carboxyethyllysine (CEL)

    International Nuclear Information System (INIS)

    Bergmann, R.; Helling, R.; Henle, T.; Heichert, C.; Scheunemann, M.; Maeding, P.; Wittrisch, H.; Johannsen, B.

    2002-01-01

    After synthesis of fluorine-18 labelled analogues [ 18 F]fluorobenzoylation at the α-amino group, biodistribution and elimination of individual advanced glycation end products, namely N ε -carboxymethyllysine and N ε -carboxyethyllysine, was studied in comparison to lysine in rats after intravenous injection using positron emission tomography. (orig.)

  16. The Use of Magnetic Resonance Imaging for Non-Invasive Assessment of Venofer® Biodistribution in Rats

    NARCIS (Netherlands)

    Span, Kimberley; Pieters, Ebel H.E.; Hennink, Wim E.; van der Toorn, Annette; Brinks, Vera; Dijkhuizen, Rick M.; van Tilborg, Geralda A.F.

    2018-01-01

    Purpose: The aim of this study was to determine the potential of magnetic resonance imaging to evaluate the biodistribution of exogenous iron within 24 h after one single injection of Venofer® (iron sucrose). Methods: Venofer® was evaluated in vitro for its ability to generate contrast in MR images.

  17. Biodistribution and dosimetry of 123I-mZIENT: a novel ligand for imaging serotonin transporters

    International Nuclear Information System (INIS)

    Nicol, Alice; Krishnadas, Rajeev; Champion, Sue; Tamagnan, Gilles; Stehouwer, Jeffrey S.; Goodman, Mark M.; Hadley, Donald M.; Pimlott, Sally L.

    2012-01-01

    123 I-labelled mZIENT (2β-carbomethoxy-3β-(3'-((Z)-2-iodoethenyl)phenyl)nortropane) has been developed as a radioligand for the serotonin transporter. The aim of this preliminary study was to assess its whole-body biodistribution in humans and estimate dosimetry. Three healthy controls and three patients receiving selective serotonin reuptake inhibitor (SSRI) therapy for depression were included (two men, four women, age range 41-56 years). Whole-body imaging, brain SPECT imaging and blood and urine sampling were performed. Whole-body images were analysed using regions of interest (ROIs), time-activity curves were derived using compartmental analysis and dosimetry estimated using OLINDA software. Brain ROI analysis was performed to obtain specific-to-nonspecific binding ratios in the midbrain, thalamus and striatum. Initial high uptake in the lungs decreased in later images. Lower uptake was seen in the brain, liver and intestines. Excretion was primarily through the urinary system. The effective dose was estimated to be of the order of 0.03 mSv/MBq. The organ receiving the highest absorbed dose was the lower large intestine wall. Uptake in the brain was consistent with the known SERT distribution with higher specific-to-nonspecific binding in the midbrain, thalamus and striatum in healthy controls compared with patients receiving SSRI therapy. 123 I-mZIENT may be a promising radioligand for imaging the serotonin transporters in humans with acceptable dosimetry. (orig.)

  18. Mathematics education and comparative historical studies

    Directory of Open Access Journals (Sweden)

    Wagner RODRIGUES VALENTE

    2013-11-01

    Full Text Available This paper has as its aims: to characterize the area of research «history of mathematics education» and to defend the idea that mathematics education has constituted a privileged research theme within the field of comparative historical studies. To achieve these aims, the text includes references to a review of the literature concerning comparative studies, the analysis of two fundamental moments focused on attempts to internationalize the mathematics curriculum, both of which occurred during the 20th century, and, to end, a case study emanating from an international cooperation between researchers in Brazil and Portugal.

  19. The tumour sink effect on the biodistribution of 68Ga-DOTA-octreotate: implications for peptide receptor radionuclide therapy

    International Nuclear Information System (INIS)

    Beauregard, Jean-Mathieu; Hofman, Michael S.; Kong, Grace; Hicks, Rodney J.

    2012-01-01

    Tumour sequestration of radiotracer may lead to decreased bioavailability in healthy tissue resulting in lower absorbed radiation dose to critical organs. This study aims to assess the impact of disease burden, body habitus and urinary excretion on the biodistribution of 68 Ga-DOTA-octreotate. Ten patients with highly varied burden of somatostatin receptor-positive neuroendocrine tumour on 68 Ga-DOTA-octreotate positron emission tomography (PET)/CT were selected. Volumes of interest were drawn to derive the average uptake of renal parenchyma, spleen and body background, as well as to compute the fraction of injected activity sequestered in tumour and excreted in urine. Uptake values were assessed for correlation with tumour sequestration, weight, lean body weight, body surface area and urinary excretion. There was a trend for tumour sequestration, body habitus and urinary excretion to inversely influence all healthy tissue uptake values. In particular, renal uptake, splenic intensity and background soft tissue activity were all significantly correlated to composite factors combining tumour sequestration with body habitus and renal excretion. When combined with body habitus index or a body habitus index and renal excretion, tumour sequestration was strongly and significantly correlated inversely with renal uptake. Our results suggest that tumour sequestration of 68 Ga-DOTA-octreotate is a major factor leading to a sink effect that decreases activity concentration in healthy organs such as the kidney. However, body habitus and renal function also influence tissue biodistribution, in a synergistic fashion. Compared with a fixed-dose peptide receptor radionuclide therapy protocol, an adjusted-dose regimen tailored to tumour burden, body habitus and renal function may allow greater radiation dose to individual lesions without substantially adding to toxicity in normal tissues. (orig.)

  20. Biodistribution and pharmacokinetics of a telodendrimer micellar paclitaxel nanoformulation in a mouse xenograft model of ovarian cancer

    Directory of Open Access Journals (Sweden)

    Xiao W

    2012-03-01

    Full Text Available Wenwu Xiao1, Juntao Luo2, Teesta Jain3, John Riggs3, Harry P Tseng1, Paul T Henderson3, Simon R Cherry4, Douglas Rowland4, Kit S Lam1,31Department of Biochemistry and Molecular Medicine, UC Davis Cancer Center, University of California Davis, Sacramento, CA; 2Department of Pharmacology, SUNY Upstate Cancer Research Institute, SUNY Upstate Medical University, Syracuse, NY; 3Department of Internal Medicine, Division of Hematology and Oncology, 4Department of Biomedical Engineering, UC Davis Cancer Center, University of California Davis, Davis, CABackground: A multifunctional telodendrimer-based micelle system was characterized for delivery of imaging and chemotherapy agents to mouse tumor xenografts. Previous optical imaging studies demonstrated qualitatively that these classes of nanoparticles, called nanomicelles, preferentially accumulate at tumor sites in mice. The research reported herein describes the detailed quantitative imaging and biodistribution profiling of nanomicelles loaded with a cargo of paclitaxel.Methods: The telodendrimer was covalently labeled with 125I and the nanomicelles were loaded with 14C-paclitaxel, which allowed measurement of pharmacokinetics and biodistribution in the mice using microSPECT/CT imaging and liquid scintillation counting, respectively.Results: The radio imaging data showed preferential accumulation of nanomicelles at the tumor site along with a slower clearance rate than paclitaxel formulated in Cremophor EL (Taxol®. Liquid scintillation counting confirmed that 14C-labeled paclitaxel sequestered in nanomicelles had increased uptake by tumor tissue and slower pharmacokinetics than Taxol.Conclusion: Overall, the results indicate that nanomicelle-formulated paclitaxel is a potentially superior formulation compared with Taxol in terms of water solubility, pharmacokinetics, and tumor accumulation, and may be clinically useful for both tumor imaging and improved chemotherapy applications

  1. The tumour sink effect on the biodistribution of {sup 68}Ga-DOTA-octreotate: implications for peptide receptor radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Beauregard, Jean-Mathieu [Peter MacCallum Cancer Centre and University of Melbourne, Centre for Cancer Imaging, Melbourne (Australia); Centre hospitalier universitaire de Quebec and Laval University, Molecular Imaging Research Group, Medical Imaging Department, Quebec City, QC (Canada); Hofman, Michael S.; Kong, Grace; Hicks, Rodney J. [Peter MacCallum Cancer Centre and University of Melbourne, Centre for Cancer Imaging, Melbourne (Australia)

    2012-01-15

    Tumour sequestration of radiotracer may lead to decreased bioavailability in healthy tissue resulting in lower absorbed radiation dose to critical organs. This study aims to assess the impact of disease burden, body habitus and urinary excretion on the biodistribution of {sup 68}Ga-DOTA-octreotate. Ten patients with highly varied burden of somatostatin receptor-positive neuroendocrine tumour on {sup 68}Ga-DOTA-octreotate positron emission tomography (PET)/CT were selected. Volumes of interest were drawn to derive the average uptake of renal parenchyma, spleen and body background, as well as to compute the fraction of injected activity sequestered in tumour and excreted in urine. Uptake values were assessed for correlation with tumour sequestration, weight, lean body weight, body surface area and urinary excretion. There was a trend for tumour sequestration, body habitus and urinary excretion to inversely influence all healthy tissue uptake values. In particular, renal uptake, splenic intensity and background soft tissue activity were all significantly correlated to composite factors combining tumour sequestration with body habitus and renal excretion. When combined with body habitus index or a body habitus index and renal excretion, tumour sequestration was strongly and significantly correlated inversely with renal uptake. Our results suggest that tumour sequestration of {sup 68}Ga-DOTA-octreotate is a major factor leading to a sink effect that decreases activity concentration in healthy organs such as the kidney. However, body habitus and renal function also influence tissue biodistribution, in a synergistic fashion. Compared with a fixed-dose peptide receptor radionuclide therapy protocol, an adjusted-dose regimen tailored to tumour burden, body habitus and renal function may allow greater radiation dose to individual lesions without substantially adding to toxicity in normal tissues. (orig.)

  2. Comparative study of bioethanol production from sugarcane ...

    African Journals Online (AJOL)

    The study was designed to compare the bioethanol production from Zymomonas mobilis and Saccharomyces cerevisiae using molasses as production medium. The focus was on the retention time at lab scale. Bioethanol and petroleum blend can be used in existing gasoline engines. Present study showed a more ...

  3. Supplementary data: Comparative studies on sequence ...

    Indian Academy of Sciences (India)

    Unknown

    Page 1. Supplementary data: Comparative studies on sequence characteristics around translation initiation codon in four eukaryotes. Qingpo Liu and Qingzhong Xue. J. Genet. 84, 317–322. Table 1. Spearman's rank correlation coefficients of 39 base positions around the AUG codon in the four eukaryotic species studied.

  4. Comparative study of native and irradiated crotoxin. Biochemical and pharmacological effects

    International Nuclear Information System (INIS)

    Nascimento, N. do.

    1991-01-01

    Ionizing radiation is able to detoxify several venoms, including snake venom, without affecting significantly their antigenic and immunogenic properties. In order to elucidate this phenomena, we conceived a comparative biochemical and pharmacological study between native and gamma irradiated (2000Gy) crotoxin, main toxin of south american rattlesnake Crotalus durissus terrificus. Crotoxin was isolated and purified from crude venom by molecular exclusion chromatography, pI precipitation and then irradiated. Immunodiffusion, electrophoresis and gel filtration showed that the molecular integrity was preserved after irradiation with some higher molecular weight aggregate formation and maintenance of its antigenic capacity. The antibodies induced by irradiated toxin had a similar titer to the antibodies induced by native crotoxin; however with higher protective effects in mice. Crotoxin toxicity became 15 times lower after irradiation, as determined by LD sub(50) in mice. Native and irradiated crotoxin biodistribution occurred with a similar general pattern, with renal elimination. In contrast to irradiated crotoxin, the native crotoxin is initially retained in kidneys. A later concentration (2-3hs) occurs in phagocyticmononuclear cells rich organs (liver and spleen) and neural junctions rich organs (muscle and brain). (author)

  5. Comparative Studies: historical, epistemological and methodological notes

    Directory of Open Access Journals (Sweden)

    Juan Ignacio Piovani

    2017-09-01

    Full Text Available In this article some historical, epistemological and methodological issues related to comparative studies in the social sciences are addressed, with specific reference to the field of education. The starting point is a discussion of the meaning of comparison, its logical structure and its presence in science and in everyday life. It follows the presentation and critical appraisal of the perspectives regarding comparison as a scientific method. It is argued that, even rejecting this restrictive meaning of comparison as a method, there is some consensus on the specificity of comparative studies within the social sciences. And in relation to them, the article address in more detail those studies that can be defined as trans-contextual (cross-national and cross-cultural, with emphasis on the main methodological and technical challenges they face. The socio-historical comparative perspective, which has gained importance in recent years in the field of education, is also discussed.

  6. A Comparative Study on Error Analysis

    DEFF Research Database (Denmark)

    Wu, Xiaoli; Zhang, Chun

    2015-01-01

    Title: A Comparative Study on Error Analysis Subtitle: - Belgian (L1) and Danish (L1) learners’ use of Chinese (L2) comparative sentences in written production Xiaoli Wu, Chun Zhang Abstract: Making errors is an inevitable and necessary part of learning. The collection, classification and analysis...... the occurrence of errors either in linguistic or pedagogical terms. The purpose of the current study is to demonstrate the theoretical and practical relevance of error analysis approach in CFL by investigating two cases - (1) Belgian (L1) learners’ use of Chinese (L2) comparative sentences in written production...... of errors in the written and spoken production of L2 learners has a long tradition in L2 pedagogy. Yet, in teaching and learning Chinese as a foreign language (CFL), only handful studies have been made either to define the ‘error’ in a pedagogically insightful way or to empirically investigate...

  7. A comparative study of map use

    DEFF Research Database (Denmark)

    Bouvin, Niels Olof; Brodersen, Ann Christina; Bødker, Susanne

    2006-01-01

    We present a study comparing the handling of three kinds of maps, each on a physical device: a paper map, a tablet-PC based map, and a cellular phone based one. Six groups of users were asked to locate eight landmarks, looking out a window, and using a particular map. We have begun analyzing video...

  8. A comparative study of microbiological and physicochemical ...

    African Journals Online (AJOL)

    A comparative study of microbiological and physicochemical characteristics of water distributed from two water treatment plants in Rwanda. ... Thus, as recommendation to WASAC authority, there is a need for improvement in the water management strategy for better water quality especially along the distribution network.

  9. Comparative study of quantum anharmonic potentials

    International Nuclear Information System (INIS)

    Amore, Paolo; Aranda, Alfredo; De Pace, Arturo; Lopez, Jorge A.

    2004-01-01

    We perform a study of various anharmonic potentials using a recently developed method. We calculate both the wave functions and the energy eigenvalues for the ground and first excited states of the quartic, sextic and octic potentials with high precision, comparing the results with other techniques available in the literature

  10. Comparative study of potato cultivation through micropropagation ...

    African Journals Online (AJOL)

    sonu

    Comparative study of potato cultivation through micropropagation and conventional farming methods .... and Murate potash were used as fertilizer source of nitrogen, phosphorus and potassium, respectively (Table 1) ..... through Tissue culture- Application and Feasibility. U.S.D.A.,. Beltsville. Agric. Res. Sci. Educ. Admin.

  11. Influence of sweeteners in the biodistribution of radiopharmaceutical ...

    African Journals Online (AJOL)

    Influence of sweeteners in the biodistribution of radiopharmaceutical and laboratory tests in rats. Michelly Pires Queiroz, Vanessa Santos de Arruda Barbosa, Cecília Maria de Carvalho Xavier Holanda, Janette Monroy Osório, Tarciso Bruno Montenegro Sampaio, Christina da Silva Camillo, Aldo Cunha Medeiros, Marília ...

  12. AMERICAN EDUCATION SYSTEM: A COMPARATIVE STUDY

    OpenAIRE

    BAS, Gökhan

    2016-01-01

    The purpose of this study was to introduce the Education System of the United States of America (USA) and to compare it with the Turkish Education System. The Education System of the United States of America was held from different factors (e.g., education structure, curriculum and instruction, principal selection, educational supervision, special education ,teacher education, finance for education, international examinations, vs.) and these factors were explained under headlines in the study...

  13. Comparative studies of D2 receptors and cerebral blood flow in hemi-parkinsonism rats

    International Nuclear Information System (INIS)

    Lin, Y.; Lin, X.

    2000-01-01

    To study the relationship between dopamine (DA) D 2 receptors and cerebral blood flow in hemiparkinsonism rats. Hemi-parkinsonism rats were made by stereotaxic 6-hydroxy dopamine (6-OH-DA) lesions in substantia nigra and ventral tegmental area, apomorphine (Apo) which could induce the successful model rat rotates toward the intact side was used to screen that rats, 125 I-IBZM in vivo autoradiography and 99m Tc-HM-PAO regional brain biodistribution were used to study D 2 receptors and cerebral blood flow. The HPLC-ECD were used to measure the concentration of DA and it metabolites homovanillic acid (HVA), 3,4-dehydroxyphenyl acetic acid (DOPAC) in bilateral striatum (ST). The lesioned side ST DA and its metabolites HVA DOPAC reduced significantly than that of the intact side and pseudo-operated control group, ST/cerebellum (CB) 125 I-IBZM uptake ratio was 8.04 ±0.71 in lesioned side of hemi-parkinsonism rats, significantly increased compared with the intact side and the pseudo-operated group (p 99m Tc 30.1±4.53% enhancement as compared to the intact side, and also show good correlation with 30 min Apo induced rotation numbers (r=0.98), the regional cerebral blood flow study didn't show significant difference between bilateral brain cortex area (p>0.05). The DA content decreased significantly and induced an up-regulation of ST D 2 receptor binding sites in 6-OH-DA lesioned side in hemi-parkinsonism rats, the increased percentage of lesioned-intact side ST/CB 125 I-IBZM uptake ratio showed good correlation with rotation behavior induced by Apo. Compare with cerebral blood flow, D 2 receptor reflected by IBZM seems to be more specific and earlier to detect the cerebral functional impairment in experimental hemi-parkinsonism

  14. A comparative study of various advanced fusions

    International Nuclear Information System (INIS)

    Momota, H.; Tomita, Y.; Nomura, Y.

    1983-01-01

    For the purpose of comparing the merits and demerits of various advanced fuel cycles, parametric studies of operation conditions are examined. The effects of nuclear elastic collisions and synchrotron radiation are taken into account. It is found that the high-#betta# Catalyzed DD fuel cycle with the transmutation of fusion-produced tritium into helium-3 is most feasible from the point of view of neutron production and tritium handling. The D-D fuel cycles seem to be less attractive compared to the Catalyzed DD. The p- 11 B and p- 6 Li fusion plasmas hardly attain the plasma Q value relevant to reactors. (author)

  15. A comparative study of Averrhoabilimbi extraction method

    Science.gov (United States)

    Zulhaimi, H. I.; Rosli, I. R.; Kasim, K. F.; Akmal, H. Muhammad; Nuradibah, M. A.; Sam, S. T.

    2017-09-01

    In recent year, bioactive compound in plant has become a limelight in the food and pharmaceutical market, leading to research interest to implement effective technologies for extracting bioactive substance. Therefore, this study is focusing on extraction of Averrhoabilimbi by different extraction technique namely, maceration and ultrasound-assisted extraction. Fewplant partsof Averrhoabilimbiweretaken as extraction samples which are fruits, leaves and twig. Different solvents such as methanol, ethanol and distilled water were utilized in the process. Fruit extractsresult in highest extraction yield compared to other plant parts. Ethanol and distilled water have significant role compared to methanol in all parts and both extraction technique. The result also shows that ultrasound-assisted extraction gave comparable result with maceration. Besides, the shorter period on extraction process gives useful in term of implementation to industries.

  16. Environmental Comparative Risk Assessment: A Case Study

    International Nuclear Information System (INIS)

    Ali, M.M.

    2007-01-01

    Health and environmental impacts associated with energy production and industrial activities as well as food production and agricultural activities have had great concern in the last decades. Early activities emerged in late 80s of the last century through an Inter- Agency project (lAEA, UNDY, WHO, ... ) on the comparative risk assessment from energy systems and industrial complexes. A work-shop on Risk Assessment and Management in large industrial areas was held in Alexandria Egypt on 20-33 Det 1993, sponsored by IAEA. Several conferences, experts work groups and workshops were held there of Recent trends in determining risks are: 1. Use of probabilistic risk assessment approach to identify hazardous activities and accident scenario. 2. development of data base on failure probabilities and appropriate physical models. 3. Development of related directives and regulations and criteria Comparative risk assessment case study as a tool for comparing risk is emphasized Criteria of exposure to human and ecological risks are addressed

  17. Comparative Study of Bancruptcy Prediction Models

    Directory of Open Access Journals (Sweden)

    Isye Arieshanti

    2013-09-01

    Full Text Available Early indication of bancruptcy is important for a company. If companies aware of  potency of their bancruptcy, they can take a preventive action to anticipate the bancruptcy. In order to detect the potency of a bancruptcy, a company can utilize a a model of bancruptcy prediction. The prediction model can be built using a machine learning methods. However, the choice of machine learning methods should be performed carefully. Because the suitability of a model depends on the problem specifically. Therefore, in this paper we perform a comparative study of several machine leaning methods for bancruptcy prediction. According to the comparative study, the performance of several models that based on machine learning methods (k-NN, fuzzy k-NN, SVM, Bagging Nearest Neighbour SVM, Multilayer Perceptron(MLP, Hybrid of MLP + Multiple Linear Regression, it can be showed that fuzzy k-NN method achieve the best performance with accuracy 77.5%

  18. Robust canonical correlations: A comparative study

    OpenAIRE

    Branco, JA; Croux, Christophe; Filzmoser, P; Oliveira, MR

    2005-01-01

    Several approaches for robust canonical correlation analysis will be presented and discussed. A first method is based on the definition of canonical correlation analysis as looking for linear combinations of two sets of variables having maximal (robust) correlation. A second method is based on alternating robust regressions. These methods axe discussed in detail and compared with the more traditional approach to robust canonical correlation via covariance matrix estimates. A simulation study ...

  19. Comparative Study on Water Impact Problem

    OpenAIRE

    Yang, Liang; Yang, Hao; Yan, Shiqiang; Ma, Qingwei; Bihnam, Maria

    2016-01-01

    This paper presents a comparative numerical study for the water impact problems due to dropping of triangular wedges or ship sections. In the numerical investigation, both the dynamic mesh technique and immersed boundary method adopting fixed Cartesian grids have been adopted in order to conform to the motion of the structure. For the former, a multiple-phase solver with the volume of fluid for identifying the free surface is implemented. In the simulation using this method, both the compress...

  20. Linear pneumatic motors – a comparative study

    Directory of Open Access Journals (Sweden)

    Deaconescu Tudor

    2017-01-01

    Full Text Available The paper presents a comparative study of the performance of single-acting cylinders, diaphragm cylinders and pneumatic muscles, and offers users information that allows the selection of an optimum technical solution. Such a study was necessary, in view of the numerous papers on pneumatic muscle applications found in literature, that assert the superiority of pneumatic muscles over other pneumatic linear motors in relation to quantities like dimensions, mass, developed force or energy-to-mass ratios, however without offering concrete data.

  1. A comparative study of two shovel designs.

    Science.gov (United States)

    Degani, A; Asfour, S S; Waly, S M; Koshy, J G

    1993-10-01

    In the present study a modified shovel design with two perpendicular shafts is presented. This modified, two-shaft shovel was compared with a regular shovel. The modified shovel was evaluated and tested in a controlled laboratory environment using surface electromyography recorded from the lumbar paraspinal muscles. The new shovel design was also tested in a field study using ratings of perceived exertion. The results indicate that there was a significant reduction in EMG values of the lumbar paraspinal muscles and a consistent reduction in perceived exertion ratings while the modified shovel was being used for removing dirt in digging trenches up to 90 cm in depth.

  2. [Nonprocess autism in children: comparative etiopathogenetic study].

    Science.gov (United States)

    Kagan, V E

    1979-01-01

    Etiopathogenesis of the childhood autism syndrome of a non-process nature is discussed on the basis of a comparative study of 156 children aged from 3 to 16 years. In the etiological complex there is a prevalence of early exogenous-organic noxious factors, which is reflected in disturbances of mental divelopment, maturation of the system of hemispheric pair work. The data of follow-up studies and treatment confirm a conclusion about a residual-organic basis in the syndrome of childhood autism.

  3. Effect of glycosylation on biodistribution of radiolabeled glucagon-like peptide 1

    International Nuclear Information System (INIS)

    Watanabe, Ayahisa; Nishijima, Ken-ichi; Zhao, Songji; Tamaki, Nagara; Kuge, Yuji; Tanaka, Yoshikazu; Itoh, Takeshi; Takemoto, Hiroshi

    2012-01-01

    Glycosylation is generally applicable as a strategy for increasing the activity of bioactive proteins. In this study, we examined the effect of glycosylation on biodistribution of radiolabeled glucagon-like peptide 1 (GLP-1) as a bioactive peptide for type 2 diabetes. Noninvasive imaging studies were performed using a gamma camera after the intravenous administration of 123 I-GLP-1 or 123 I-α2, 6-sialyl N-acetyllactosamine (glycosylated) GLP-1 in rats. In ex vivo biodistribution studies using 125 I-GLP-1 or 125 I-glycosylated GLP-1, organ samples were measured for radioactivity. Plasma samples were added to 15% trichloroacetic acid (TCA) to obtain TCA-insoluble and TCA-soluble fractions. The radioactivity in the TCA-insoluble and TCA-soluble fractions was measured. In the noninvasive imaging studies, a relatively high accumulation level of 123 I-GLP-1 was found in the liver, which is the major organ to eliminate exogenous GLP-1. The area under the time-activity curve (AUC) of 123 I-glycosylated GLP-1 in the liver was significantly lower (89%) than that of 123 I-GLP-1. These results were consistent with those of ex vivo biodistribution studies using 125 I-labeled peptides. The AUC of 125 I-glycosylated GLP-1 in the TCA-insoluble fraction was significantly higher (1.7-fold) than that of GLP-1. This study demonstrated that glycosylation significantly decreased the distribution of radiolabeled GLP-1 into the liver and increased the concentration of radiolabeled GLP-1 in plasma. These results suggested that glycosylation is a useful strategy for decreasing the distribution into the liver of bioactive peptides as desirable pharmaceuticals. (author)

  4. Altered biodistribution of FDG in patients with type-2 diabetes mellitus

    International Nuclear Information System (INIS)

    Ozguven, M.A.; Karacalioglu, A.O.; Ince, S.; Emer, M.O.

    2014-01-01

    Positron emission tomography-computed tomography (PET-CT) imaging of patients with diabetes can be problematic because elevated glucose levels may cause competitive inhibition of [F-18]-2-deoxy-2-fluoro-D-glucose (FDG) uptake in different tissues. Therefore, the aim of the study was to evaluate the biodistribution of FDG in patients with type-2 diabetes mellitus. Two hundred forty patients were retrospectively enrolled to the study. Study population was divided into three subgroups, named as the normal (group 1), the insulin (group 2) and the oral anti-diabetic (group 3). Unenhanced low-dose CT and PET emission data were acquired from the mid-thigh to the vertex of the skull. FDG uptakes in different organs were evaluated qualitatively or semi-quantitatively. In the diabetic groups, diffuse FDG uptake of the colon was increased (p > 0.001) but segmental FDG uptake was decreased (p > 0.001). Intestinal FDG uptake was detected in 20% of the study population and only 3% of these uptakes were in diffuse pattern. Segmental FDG uptake in the bowel was increased significantly in the groups of patients with diabetes (p = 0.002). Maximum standardized uptake values of the liver in the groups 1, 2, and 3 were 2.66 ± 0.6, 3.25 ± 0.9 and 3.16 ± 0.8, respectively, and the difference between the groups was not statistically significant (p = 0.083). Cardiac FDG uptake was decreased significantly in the groups of patients with diabetes (p < 0.001). According to our results, whole body bio-distribution of FDG uptake seems to be changed in patients with type-2 diabetes who were using insulin or oral anti-diabetic drugs. Although the use of oral antidiabetic drugs was known to change the biodistribution of FDG, insulin use also seems to change FDG uptake in different organs of diabetic patients. (author)

  5. Comparative Study of Daylighting Calculation Methods

    Directory of Open Access Journals (Sweden)

    Mandala Ariani

    2018-01-01

    Full Text Available The aim of this study is to assess five daylighting calculation method commonly used in architectural study. The methods used include hand calculation methods (SNI/DPMB method and BRE Daylighting Protractors, scale models studied in an artificial sky simulator and computer programs using Dialux and Velux lighting software. The test room is conditioned by the uniform sky conditions, simple room geometry with variations of the room reflectance (black, grey, and white color. The analyses compared the result (including daylight factor, illumination, and coefficient of uniformity value and examines the similarity and contrast the result different. The color variations trial is used to analyses the internally reflection factor contribution to the result.

  6. Risk indices in comparative risk assessment studies

    International Nuclear Information System (INIS)

    Hubert, P.

    1984-01-01

    More than a decade ago the development of comparative risk assessment studies aroused overwhelming interest. There was no doubt that data on the health and safety aspects of energy systems would greatly benefit, or even end, the debate on nuclear energy. Although such attempts are still strongly supported, the rose-coloured expectations of the early days have faded. The high uncertainties, and the contradictory aspect, of the first results might explain this evolution. The loose connection between the range of computed risk indices and the questions on which the debate was focused is another reason for this decline in interest. Important research work is being carried out aiming at reducing the different kinds of uncertainties. Rather than the uncertainties, the paper considers the meaning of available risk indices and proposes more significant indices with respect to the goals of risk assessment. First, the indices which are of frequent use in comparative studies are listed. The stress is put on a French comparative study from which most examples are drawn. Secondly, the increase in magnitude of the indices and the decrease in the attributability of the risk to a given system is shown to be a consequence of the trend towards more comprehensive analyses. Thirdly, the ambiguity of such indices as the collective occupational risk is underlined, and a possible solution is suggested. Whenever risk assessments are related to pragmatic decision making problems it is possible to find satisfactory risk indices. The development of cost-effectiveness analyses and the proposals for quantitative safety goals clearly demonstrate this point. In the field of comparison of social impacts some proposals are made, but there remain some gaps still to be filled. (author)

  7. EFQPSK Versus CERN: A Comparative Study

    Science.gov (United States)

    Borah, Deva K.; Horan, Stephen

    2001-01-01

    This report presents a comparative study on Enhanced Feher's Quadrature Phase Shift Keying (EFQPSK) and Constrained Envelope Root Nyquist (CERN) techniques. These two techniques have been developed in recent times to provide high spectral and power efficiencies under nonlinear amplifier environment. The purpose of this study is to gain insights into these techniques and to help system planners and designers with an appropriate set of guidelines for using these techniques. The comparative study presented in this report relies on effective simulation models and procedures. Therefore, a significant part of this report is devoted to understanding the mathematical and simulation models of the techniques and their set-up procedures. In particular, mathematical models of EFQPSK and CERN, effects of the sampling rate in discrete time signal representation, and modeling of nonlinear amplifiers and predistorters have been considered in detail. The results of this study show that both EFQPSK and CERN signals provide spectrally efficient communications compared to filtered conventional linear modulation techniques when a nonlinear power amplifier is used. However, there are important differences. The spectral efficiency of CERN signals, with a small amount of input backoff, is significantly better than that of EFQPSK signals if the nonlinear amplifier is an ideal clipper. However, to achieve such spectral efficiencies with a practical nonlinear amplifier, CERN processing requires a predistorter which effectively translates the amplifier's characteristics close to those of an ideal clipper. Thus, the spectral performance of CERN signals strongly depends on the predistorter. EFQPSK signals, on the other hand, do not need such predistorters since their spectra are almost unaffected by the nonlinear amplifier, Ibis report discusses several receiver structures for EFQPSK signals. It is observed that optimal receiver structures can be realized for both coded and uncoded EFQPSK

  8. Comparative study of angio genesis radiopharmaceuticals for melanoma detection

    International Nuclear Information System (INIS)

    Oliveira, Erica Aparecida de

    2011-01-01

    Early diagnosis and treatment of melanoma, a cutaneous tumor with a serious prognosis, is extremely important for optimal clinical outcome. Phage display peptide libraries are a useful screening resource for identifying bioactive peptides that interact with cancer targets. The aim of this study was the evaluation of two technetium-99m tracers for angio genesis detection in melanoma model, using cyclic peguilated pentapeptide with RGD and NGR motifs conjugated with bifunctional chelator MAG3. The conjugated peptides (10 μL of a μg/μL solution) were labeled with technetium-99m using a sodium tartrate buffer. Radiochemical evaluation was done by ITLC and confirmed by HPLC. Partition coefficient was determined and internalization assays were performed in two melanoma cells (B16F10 and SKMEL28). Biodistribution evaluation of the tracers was done in healthy animals at different times and also in mice bearing the tumor cells at 120 min post injection. Blocking studies were also conducted by co-injection of cold peptides. The conjugated showed the same profile in many evaluations. They were radiolabeled with high radiochemical purity (>97%). Both were hydrophilic, with preferential renal excretion. Tumor uptake was higher for human melanoma cells than for murinic melanoma cells, specially for 99m Tc-MAG3-PEG 8 -c(RGDyK) (7.85±±2.34 %ID/g) at 120 min post injection. The performance of 99m Tc-MAG 3 -PEG 8 -c(RGDyk) was much better than NGR tracer concerning human melanoma uptake and might be considered in future investigations focusing radiotracers for melanoma diagnosis. (author)

  9. CURRICULAR OFFER INFLUENCING STUDENTS’ SATISFACTION: COMPARATIVE STUDY

    Directory of Open Access Journals (Sweden)

    Oana DUMITRASCU

    2014-11-01

    Full Text Available The main objective of the study is the determination of students’ satisfaction regarding curricular activities. The study has been accomplished using the qualitative and quantitative research, using the bibliographic study, various secondary sources and different primary sources. The study is developed with a marketing research and accomplished using the survey method. 699 students from four universities have been questioned. Due to a comparative study the University of Applied Sciences Worms, University of Applied Sciences Wiesbaden Rüsselsheim, University of Applied Sciences Frankfurt am Main and Nürtingen-Geislingen University have been analysed and their similarities and differences have been identified. The collected data, based on the established sample, is evaluated through univariate and bivariate analysis. In accordance with the evaluated sample, specific gaps from each region are identified regarding the curricular offer of the analysed universities. As a result to the conducted study, recommendations for the University of Applied Sciences Worms regarding the student’s satisfaction concerning the curricular offer are presented.

  10. {sup 68}Ga-DOTA-RGD peptide: biodistribution and binding into atherosclerotic plaques in mice

    Energy Technology Data Exchange (ETDEWEB)

    Haukkala, Johanna; Laitinen, Iina; Luoto, Pauliina; Knuuti, Juhani [University of Turku, Turku PET Centre, Turku (Finland); Iveson, Peter; Wilson, Ian [Medical Diagnostics, GE Healthcare Biosciences, London (United Kingdom); Karlsen, Hege; Cuthbertson, Alan [GE Healthcare MDx Research, Oslo (Norway); Laine, Jukka [Turku University Hospital, Department of Pathology, Turku (Finland); Leppaenen, Pia; Ylae-Herttula, Seppo [University of Kuopio, A.I. Virtanen Institute, Kuopio (Finland); Roivainen, Anne [University of Turku, Turku PET Centre, Turku (Finland); University of Turku, Turku Centre for Disease Modelling, Turku (Finland)

    2009-12-15

    Increased expression of {alpha}v{beta}3/{alpha}v{beta}5 integrin is involved in angiogenesis and the inflammatory process in atherosclerotic plaques. The novel {sup 68}Ga-DOTA-RGD peptide binds with high affinity to {alpha}v{beta}3/{alpha}v{beta}5 integrin. The aim of this study was to investigate the uptake of the {sup 68}Ga-DOTA-RGD peptide in atherosclerotic plaques. Uptake of intravenously administered {sup 68}Ga-DOTA-RGD peptide was studied ex vivo in excised tissue samples and aortic sections of LDLR{sup -/-}ApoB{sup 100/100} atherosclerotic mice. The uptake of the tracer in aortic cryosections was examined by using digital autoradiography. Subsequently, the autoradiographs were combined with histological and immunohistological analysis of the sections. DOTA-RGD peptide was successfully labelled with the generator-produced {sup 68}Ga. The tracer had reasonably good specific radioactivity (8.7 {+-} 1.1 GBq/{mu}mol) and was quite stable in vivo. According to ex vivo biodistribution results, {sup 68}Ga-DOTA-RGD was cleared rapidly from the blood circulation and excreted through the kidneys to the urine with high radioactivity in the intestine, lungs, spleen and liver. Autoradiography results showed significantly higher uptake of {sup 68}Ga-DOTA-RGD peptide in the atherosclerotic plaques compared to healthy vessel wall (mean ratio {+-} SD 1.4 {+-} 0.1, p = 0.0004). We observed that {sup 68}Ga-DOTA-RGD is accumulated into the plaques of atherosclerotic mice. However, this data only shows the feasibility of the approach, while the clinical significance still remains to be proven. Further studies are warranted to assess the uptake of this tracer into human atherosclerotic plaques. (orig.)

  11. 68Ga-DOTA-RGD peptide: biodistribution and binding into atherosclerotic plaques in mice

    International Nuclear Information System (INIS)

    Haukkala, Johanna; Laitinen, Iina; Luoto, Pauliina; Knuuti, Juhani; Iveson, Peter; Wilson, Ian; Karlsen, Hege; Cuthbertson, Alan; Laine, Jukka; Leppaenen, Pia; Ylae-Herttula, Seppo; Roivainen, Anne

    2009-01-01

    Increased expression of αvβ3/αvβ5 integrin is involved in angiogenesis and the inflammatory process in atherosclerotic plaques. The novel 68 Ga-DOTA-RGD peptide binds with high affinity to αvβ3/αvβ5 integrin. The aim of this study was to investigate the uptake of the 68 Ga-DOTA-RGD peptide in atherosclerotic plaques. Uptake of intravenously administered 68 Ga-DOTA-RGD peptide was studied ex vivo in excised tissue samples and aortic sections of LDLR -/- ApoB 100/100 atherosclerotic mice. The uptake of the tracer in aortic cryosections was examined by using digital autoradiography. Subsequently, the autoradiographs were combined with histological and immunohistological analysis of the sections. DOTA-RGD peptide was successfully labelled with the generator-produced 68 Ga. The tracer had reasonably good specific radioactivity (8.7 ± 1.1 GBq/μmol) and was quite stable in vivo. According to ex vivo biodistribution results, 68 Ga-DOTA-RGD was cleared rapidly from the blood circulation and excreted through the kidneys to the urine with high radioactivity in the intestine, lungs, spleen and liver. Autoradiography results showed significantly higher uptake of 68 Ga-DOTA-RGD peptide in the atherosclerotic plaques compared to healthy vessel wall (mean ratio ± SD 1.4 ± 0.1, p = 0.0004). We observed that 68 Ga-DOTA-RGD is accumulated into the plaques of atherosclerotic mice. However, this data only shows the feasibility of the approach, while the clinical significance still remains to be proven. Further studies are warranted to assess the uptake of this tracer into human atherosclerotic plaques. (orig.)

  12. 188Re labeling and biodistribution of magnetic nanoparticles for the tumor targeting

    International Nuclear Information System (INIS)

    Li Guiping; Zhang Hui; Wang Yongxian; Zhang Chunfu

    2006-01-01

    Objective: To prepare 188 Re labeled monoclonal antibody (Herceptin)-coated magnetic nanoparticles for tumor targeting and to study its biodistribution in mice. Methods: Herceptin and histidine were covalently linked to the amine group upon silica-coated magnetic nanoparticles modified by N-[3-(trimethyoxysilyl)prowl]-ethylenediamine using glutaraldehyde method. The Herceptin-coated magnetic nanoparticles and Herceptin were radiolabeled with 188 Re by a direct labelling method, whereas the histidine-coated magnetic nanoparticles was radiolabeled with 188 Re using fac-[ 188 Re(CO) 3 (H 2 0) 3 ] + as a precursor. The labelling efficiency and immunoreactivity as well as labelling stability were determined. Also, the biodistribution of 188 Re-magnetic and 188 Re-Herceptin-magnetic nanoparticles were observed in mice. Results: Herceptin-coated magnetic nanoparticles was characterized by transmission electron microscope (TEM) with diameter about 60 nm, while histidine-coated magnetic nanoparticles about 30 nm. The labeling efficiency for 188 Re-Herceptin, 188 Re-magnetic nanoparticles and 188 Re-Herceptin-magnetic nanoparticles were all > 90% and had a better stability in vitro. The immunoreactivity of Herceptin linked to magnetic nanoparticles was still high. The biodistribution in mice was shown that 188 Re-magnetic nanoparticles and 188 Re-Herceptin- magnetic nanoparticles had higher radioactivity levels in blood. Magnetic nanoparticles with diameter of 30 or 60 nm had a long half-life in blood stream and were accumulated in liver. Conclusion: The efficiency and stability of labelling Herceptin-coated magnetic nanoparticles and labelling magnetic nanoparticles with 188 Re are suitable for in vivo study in tumor-beating nude mice models. (authors)

  13. Dimercaptosuccinic acid-Tc99m: Preparation and biodistribution in rats

    International Nuclear Information System (INIS)

    Smal, F.; Englebienne, P.

    1976-01-01

    Owing to the juxtaposition of 4 ligands (2 SH groups + 2 COOH groups), dimercaptosuccinic acid has a strong chelating capacity which suits it for technetium 99 m labelling. The study is carried out in 2 stages: preparation and stability of the dimercaptosuccinic acid - stannous chloride complex (DMSA-Sn); biodistribution of DMSA-Sn-Tc99m complex in rats as a function of the following parameters: pH, relative stannous chloride and dimercaptosuccinic acid concentrations, TcO 4 volume added, injection time after labelling. The strong activity uptake obtained in rat kidneys represents a considerable step forward in the radioisotopic kidney examination and offers the prospect of clinical use [fr

  14. Biodistribution of doxorubicin and nanostructured ferrocarbon carrier particles in organism during magnetically controlled drug delivery

    Energy Technology Data Exchange (ETDEWEB)

    Kuznetsov, Anatoly A.; Filippov, Victor I.; Nikolskaya, Tatiana A. [Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, Moscow 119991 (Russian Federation); Budko, Andrei P. [Oncological Center, Russian Academy of Medical Sciences, Moscow (Russian Federation); Kovarskii, Alexander L. [Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, Moscow 119991 (Russian Federation); Zontov, Sergei V. [Oncological Center, Russian Academy of Medical Sciences, Moscow (Russian Federation); Kogan, Boris Ya. [Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, Moscow 119991 (Russian Federation); Kuznetsov, Oleg A. [Institute of Biochemical Physics, Russian Academy of Sciences, Kosygin St. 4, Moscow 119991 (Russian Federation)], E-mail: kuznetsov_oa@yahoo.com

    2009-05-15

    Biodistribution of doxorubicin and ferrocarbon carrier particles in organism during and after magnetically controlled anti-tumor drug delivery and deposition was studied. Animal tests show high concentration of the cytostatic drug in the target zone, while its concentration is three orders of magnitude lower in bloodstream and other organs. A significant depot of the drug remains on the deposited particles days after the procedure. Macrophages actively phagocytose the ferrocarbon (FeC) particles and remain viable long enough to carry them to the lymph nodes.

  15. Biodistribution of doxorubicin and nanostructured ferrocarbon carrier particles in organism during magnetically controlled drug delivery

    International Nuclear Information System (INIS)

    Kuznetsov, Anatoly A.; Filippov, Victor I.; Nikolskaya, Tatiana A.; Budko, Andrei P.; Kovarskii, Alexander L.; Zontov, Sergei V.; Kogan, Boris Ya.; Kuznetsov, Oleg A.

    2009-01-01

    Biodistribution of doxorubicin and ferrocarbon carrier particles in organism during and after magnetically controlled anti-tumor drug delivery and deposition was studied. Animal tests show high concentration of the cytostatic drug in the target zone, while its concentration is three orders of magnitude lower in bloodstream and other organs. A significant depot of the drug remains on the deposited particles days after the procedure. Macrophages actively phagocytose the ferrocarbon (FeC) particles and remain viable long enough to carry them to the lymph nodes.

  16. Modeling of biodistribution of 90 Y-DOTA-hR3 by using artificial intelligence techniques

    International Nuclear Information System (INIS)

    Ondarse, Dianelys; Quiza, Ramon; Leyva, Rene; Zamora, Minely; Ducat, Luis; Hernandez, Ignacio; Alonso, Luis Michel

    2011-01-01

    In this work the biodistribution of radioimmunoconjugate 9 0Y-DOTA-hR3 was modeled by using an artificial neural network. In vivo stability of 9 0Y-DOTA-hR3 was determined in healthy male Wistar rats at 4, 24 and 48 hours, in different organs. A model describing the relationship between, by one hand, the incorporated dose and, by the other hand, organ and time was developed by using a multilayer perceptron neural network. Adjusted model was analyzed by several statistical tests. Outcomes shown that proposed neural model describes the relationship between the studied variables in a proper way. (Author)

  17. Synthesis, radioiodination, and biodistribution of some nido- and closo-monocarbon carborane derivatives

    International Nuclear Information System (INIS)

    Wilbur, D. Scott; Hamlin, Donald K.; Srivastava, Rajiv R.; Chyan, Ming-Kuan

    2004-01-01

    Iodination and radioiodination reactions of several anionic nido- and closo-monocarbon carboranes were conducted. Iodinations occurred more rapidly with nido-carboranes than with closo-carboranes. The most rapid iodination and radioiodination reactions occurred with unsubstituted carboranes. C-amino and C-ammonium derivatives did not iodinate under the conditions studied. Both nido- and closo-carboranes with C-NH-acetyl and C-NH-succinyl substituents iodinated, but the nido-carboranes iodinated under milder reaction conditions. Biodistributions of nido-1-succinylamido-[ 131 I]carborane and closo-1-succinylamido-[ 125 I]carborane were similar in mice, but blood clearance of the nido- compound was slower

  18. Synthesis, quality control and biodistribution of 99mTc-Kanamycin

    International Nuclear Information System (INIS)

    Roohi, S.; Mushtaq, A.; Jehangir, M.; Malik, S.A.

    2006-01-01

    Kanamycin is an antibiotic used for treatment of infections when penicillin or other less toxic drugs cannot be used. Kanamycin was labeled with technetium-99m pertechnetate using SnCl 2 x 2H 2 O as reducing agent. The labeling efficiency depends on the ligand/reductant ratio, pH, and volume of reaction mixture. Radiochemical purity and stability of 99m Tc-Kanamycin was determined by thin layer chromatography. Biodistribution studies of 99m Tc-Kanamycin were performed in rats and rabbits. A significantly higher accumulation of 99m Tc-Kanamycin was seen at sites of S. aureus infected animals (rat/rabbit). (author)

  19. Scatterometry or imaging overlay: a comparative study

    Science.gov (United States)

    Hsu, Simon C. C.; Pai, Yuan Chi; Chen, Charlie; Yu, Chun Chi; Hsing, Henry; Wu, Hsing-Chien; Kuo, Kelly T. L.; Amir, Nuriel

    2015-03-01

    Most fabrication facilities today use imaging overlay measurement methods, as it has been the industry's reliable workhorse for decades. In the last few years, third-generation Scatterometry Overlay (SCOL™) or Diffraction Based Overlay (DBO-1) technology was developed, along another DBO technology (DBO-2). This development led to the question of where the DBO technology should be implemented for overlay measurements. Scatterometry has been adopted for high volume production in only few cases, always with imaging as a backup, but scatterometry overlay is considered by many as the technology of the future. In this paper we compare imaging overlay and DBO technologies by means of measurements and simulations. We outline issues and sensitivities for both technologies, providing guidelines for the best implementation of each. For several of the presented cases, data from two different DBO technologies are compared as well, the first with Pupil data access (DBO-1) and the other without pupil data access (DBO-2). Key indicators of overlay measurement quality include: layer coverage, accuracy, TMU, process robustness and robustness to process changes. Measurement data from real cases across the industry are compared and the conclusions are also backed by simulations. Accuracy is benchmarked with reference OVL, and self-consistency, showing good results for Imaging and DBO-1 technology. Process sensitivity and metrology robustness are mostly simulated with MTD (Metrology Target Designer) comparing the same process variations for both technologies. The experimental data presented in this study was done on ten advanced node layers and three production node layers, for all phases of the IC fabrication process (FEOL, MEOL and BEOL). The metrology tool used for most of the study is KLA-Tencor's Archer 500LCM system (scatterometry-based and imaging-based measurement technologies on the same tool) another type of tool is used for DBO-2 measurements. Finally, we conclude that

  20. A comparative study of teenage pregnancy.

    Science.gov (United States)

    Mahavarkar, S H; Madhu, C K; Mule, V D

    2008-08-01

    Teenage pregnancy is a global problem and is considered a high-risk group, in spite of conflicting evidence. Our objective was to compare obstetric outcomes of pregnancy in teenagers and older women. This was a retrospective study of case records of pregnancies from August 2000 to July 2001. Girls aged pregnancy outcomes in older women (19-35 years) in the same hospital. The study took place in the Government General Hospital, Sangli, India, a teaching hospital in rural India, with an annual delivery rate of over 3,500. A total of 386 teenage pregnancies were compared with pregnancies in 3,326 older women. Socioeconomic data, age, number of pregnancies, antenatal care and complications, mode of delivery, and neonatal outcomes were considered. The incidence of teenage pregnancy in the study was 10%. A significant proportion of teenage pregnant mothers were in their first pregnancies. The teenage mothers were nearly three times more at risk of developing anaemia (OR = 2.83, 95% CI = 2.2-3.7, p Teenage mothers were twice as likely to develop hypertensive problems in pregnancy (OR = 2.2, 95% CI = 1.5-3.2, p teenage pregnancies are still a common occurrence in rural India in spite of various legislations and government programmes and teenage pregnancy is a risk factor for poor obstetric outcome in rural India. Cultural practices, poor socioeconomic conditions, low literacy rate and lack of awareness of the risks are some of the main contributory factors. Early booking, good care during pregnancy and delivery and proper utilisation of contraceptive services can prevent the incidence and complications in this high-risk group.

  1. Labeling method of 17-allylamino, 17-demethoxygeldanamycin with 131I and its biodistribution in experimental animals

    International Nuclear Information System (INIS)

    Jiang Xinyu; Liu Lu; Gao Wen; Chen Daozhen; Huang Ying; Yang Min; Luo Shineng

    2008-01-01

    Objective: The aims of the study were to find out the optimal 131 I labeling method with 17-allylamino, 17-demethoxygeldanamycin (17-AAG) and also to study its biodistribution in animals. Methods: 131 I-17-AAG was prepared by the reaction of 17-AAG with Na 131 I in the presence of hydrogen peroxide. The labeling efficiency and the stability of 131 I-17-AAG were measured by paper chromatograph. The biodistribution in the ICR normal mice was observed by the blood samplings and major organs that were taken out from mice at 0.5, 1, 4, 8, 24 h after 131 I-17-AAG injection through tail veins. VX2 tumor was also implanted in rabbit liver for in vivo imaging with SPECT. Results: The optimal labeling conditions of 17-AAG with mi were determined. The labeling efficiency was 85.65%. The radiochemical purity of 131 I- 17-AAG in acetoacetate solution was (96.51 ± 0.80)% after purification and its radiochemical purity in normal saline solution was (95.57 ± 0.09)%. The radiochemical purity could keep to 90% in normal saline after 5 d at 4 degree C. The biodistribution study in normal mice showed that the uptake (percentage activity of injection dose per gram of tissue, % ID/g) in liver and kidney was less than that in cholecyst [(3.0963 ± 1.3394) %ID/g] at 0.5 h post-injection, and the uptake in stomach and intestine reached to the highest level at 4 h post-injection. The SPECT images showed that the 131 I-17-AAG was obviously concentrated in the tumor after injection at 2 h and 4 d, 6 d, 14 d with the highest tumor to non-tumor (T/NT) radioactivity ratio of 10.36. Conclusions: The labeling method of 17-AAG with 131 I was successfully established. The 131 I-17-AAG in normal saline had a good stability. The main biodistribution in mice was in digestive system and was excreted through the intestinal tract. The SPECT images showed that 131 I-17-AAG might be a potential target-directed agent to the tumor. (authors)

  2. Synthesis, radiolabeling and biodistribution of a new opioid glucuronide derivative. Ethyl-morphine glucuronide (em-glu)

    International Nuclear Information System (INIS)

    Enginar, H.

    2012-01-01

    In current study, ethyl-morphine (em) was synthesized from the morphine and glucuronidated via enzymatic mechanism. The conjugated glucuronide ethyl-morphine (em-glu) was radiolabeled with 131 I using iodogen method. The quality control studies of radiolabeled compound ( 131 I-em-glu) were done with Thin Layer Radio Chromatography to confirm the radiolabeling efficiency. Biodistribution studies of 131 I labeled em-glu were run on healthy male Albino Wistar rats. The distribution figures demonstrated that 131 I-em-glu was eliminated through the small intestine, large intestine and accumulated in urinary bladder both receptor blocked and unblocked biodistribution studies. A greater uptake of the radiolabeled substance was observed in the m.pons, hypothalamus and mid brain than in the other branches of the rats' brains. (author)

  3. Biodistribution, pharmacokinetics, and toxicity of dendrimer-coated iron oxide nanoparticles in BALB/c mice

    Directory of Open Access Journals (Sweden)

    Salimi M

    2018-03-01

    Full Text Available Marzieh Salimi,1,2 Saeed Sarkar,1,2 Samaneh Fathi,3 Ali Mohammad Alizadeh,4 Reza Saber,2,3 Fatemeh Moradi,5 Hamid Delavari6 1Department of Medical Physics and Biomedical Engineering, Tehran University of Medical Sciences, Tehran, Iran; 2Research Center of Science and Technology in Medicine, Tehran University of Medical Sciences, Tehran, Iran; 3Department of Medical Nanotechnology, Tehran University of Medical Sciences, Tehran, Iran; 4Cancer Research Center, Tehran University of Medical Sciences, Tehran, Iran; 5Department of Medical Physiology, Tehran University of Medical Sciences, Tehran, Iran; 6Department of Materials Science and Engineering, Tarbiat Modares University, Tehran, Iran Background: The possibility of using a specific nanoparticle in nanomedicine highly depends on its biodistribution profile and biocompatibility. Due to growing demand for iron oxide nanoparticles (IONPs and dendrimers in biomedical applications, this study was performed to assess the biodistribution, pharmacokinetics, and toxicity of dendrimer-coated iron oxide nanoparticles (G4@IONPs. Materials and methods: IONPs were synthesized via co-precipitation and coated with the fourth generation (G4 of polyamidoamine (PAMAM dendrimer. To determine the biodistribution, 5 mg/mL G4@IONPs suspension was intraperitoneally injected into tumor-bearing BALB/c mice, and iron levels in blood and various organs, including the lung, liver, brain, heart, tumor, and kidney, were measured by inductively coupled plasma mass spectrometry (ICP-MS at 4, 8, 12, and 24 h after injection. Also, to investigate the toxicity of G4@IONPs, different concentrations of G4@IONPs were injected into BALB/c mice, and blood, renal, and hepatic factors were measured. Furthermore, histopathological staining was performed to investigate the effect of G4@IONPs on the liver and kidney tissues. Results: The results showed that the iron content was higher in the kidney, liver, and lung tissues 24 h after

  4. A comparative study of bike lane injuries.

    Science.gov (United States)

    Wee, Jung Hee; Park, Jeong Ho; Park, Kyu Nam; Choi, Seung Pill

    2012-02-01

    Because of the increased number of bicycle riders and governmental promotions, a recent increase in the construction of bicycle lanes has occurred. We aimed to characterize injuries specific to bicycle lane accidents by comparing them with injuries that occurred on regular roadways. On the basis of our findings, we provide suggestions on proper preventive strategies. We performed a retrospective study on 408 cases obtained between January 1, 2009, and December 31, 2010. Of these cases, 387 met the criterion that the location of the injury could be confirmed by telephone or via review of the patient's chart. Data regarding age, gender, Injury Severity Score, time of the accident, location of the accident, and other characteristics were collected. Data were analyzed using SPSS 12.0K. Of the 387 cases, 204 (52.7%) patients were injured in bicycle lanes and 183 (47.3%) were injured on regular roadways. Comparing cases of bicycle lane injuries and non-bicycle lane injuries, there were no differences in age, day of the week, season, or the time at which the accident occurred. Bicycle helmets were used more frequently in bicycle lane injuries (33.2% vs. 13.7%; p cases, falls (42.6%) and collisions with other vehicles (39.3%) were the most common causes of injury. Although the severity of injuries was slightly lower in bicycle lane cases, it was not significantly lower than non-bicycle lane cases. Although people are increasingly using bicycle lanes for safety, this study shows that they are not definitively safer. Therefore, improvements in the policies related to implementing bicycle lane safety are needed, for example, by enforcing the use of protective gear or preventing the use of bicycle lanes by pedestrians. More safety education programs are also needed. III.

  5. Laproscopic versus open appendectomy: A comparative study

    International Nuclear Information System (INIS)

    Shirazi, B.; Naureen Ali, N.; Shamim, M.S.

    2010-01-01

    Objective: To compare the results of open with laparoscopic appendectomy in terms of postoperative pain, rate of wound infection and hospital stay. Methods: This quasi-experimental study was conducted in Department of Surgery, Ziauddin University Hospital, Karachi, over a period of six months. Patients undergoing surgery for acute appendicitis were randomly assigned into one of the two groups (A or B) after obtaining written and informed consent. In Group-A patients underwent open appendectomy and in Group B laparoscopic appendectomy was performed. Post operatively pain chart and wound infection was recorded and, at the time of discharge, number of days in hospital was calculated. Result: Sixty patients (38 male, 22 female), with clinical diagnosis of acute appendicitis based on Alvarado score of six and above, were included in the study. They were randomized into 2 groups of A and B with 30 patients in each group. Group-A comprised open appendectomy procedure and Group-B comprised laparoscopic appendectomy. Mean comparison of postoperative pain by visual analogue scale, was significantly low in Group B, compared with Group A, on day 0, 1 and 2. Number of days in Hospital was 4.1 +- 0.8 days in Group A and 1.5 +- 0.06 days in Group B. None of the patients in Group B, while 8 (26.67%) patients in-Group A, developed postoperative wound infection at 1 week follow up. Conclusion: Laparoscopic appendectomy is safe and effective. Wound infection and postoperative pain is significantly lower after this mode of surgery. (author)

  6. Evaluation the influence of Polyethylene glycol in circulation and biodistribution of pH-sensitive liposomes, radiolabeled with Technetium 99m in experimental models

    International Nuclear Information System (INIS)

    Nunes, Shirleide Santos

    2016-01-01

    Liposomes are lipid vesicles widely studied throughout the world as nanocarriers for different substances. The hydrophilic polymer polyethylene glycol (PEG) might be added onto the surface of liposomes to prolong the circulation time by reducing the opsonization of the vesicles, leading to a reduced uptake by the mononuclear phagocyte system (MPS). Several studies claim that the molecular weight of the PEG, as well as combination of different types of PEG with different molecular weights may alter the pharmacokinetics of the liposome. Therefore, the purpose of this study was to evaluate the influence of molecular weight and PEG combinations with different chain sizes in the pharmacokinetics and biodistribution of pH-sensitive liposomes containing 99m Tc-HYNIC-βAla-Bombesin complex (7-14 ) in tumor models (4T1 and Ehrlich). Eight liposomal formulations were prepared, the results showed that the liposomes exhibited adequate chemical and physical-chemical properties, such as mean diameter less than 300nm, monodisperse populations, neutral zeta potential, and encapsulation content of 26.4 to 38.7%. The images obtained by transmission electron cryomicroscopy (cryo-TEM) allowed visualization of unilamellar vesicles with an average diameter of 90 nm. There was no difference in blood half-life (T1/2), thereby for the composition of liposomes used in this study, PEG did not increase blood circulation time. Biodistribution studies and scintigraphic images showed high uptake by organs of the SMF, liver and spleen. The PEG2000 formulation showed higher concentration in blood. Liposomes with DSPE, PEG2000 or PEG1000 / 5000 showed higher uptake in the tumor compared to the contralateral muscle, but there was no statistical difference between the formulations when tumor-to-muscle ratio, obtained in the biodistribution studies or scintigraphic images, was analyzed. The results suggest that for this specific formulation, the addition of PEG was not efficient for increasing the

  7. Radioiodine-labeling of EGCG and its biodistribution in mice

    International Nuclear Information System (INIS)

    Diao Yao; Zhao Wenjin; Liu Jie; Zhao Xun; Yu Chengguo; Cui Zeshi; Liu Xinning; Lan Zhenhe; Ma Jing

    2013-01-01

    To establish the 125 I-EGCG labeling method and investigate the biodistribution of 125 I-EGCG in mice, 125 I-EGCG was prepared by Iodogen solid labeling method, and were isolated and purified by Sephadex-G25 agarose. The labeling yield and radiochemical purity of 125 I-EGCG was analyzed by polyamide TLC. The labeling yield of 125 I-EGCG was 89.4% and its radiochemical purity (RCP) were 96.4%. The Biodistribution of 125 I-EGCG in mice was measured at different times after caudal vein injection with 185 kBq for each mice. The biodistribution in mice demonstrated that 125 I-EGCG was distributed into broad organs and tissues, especially in the Stomach, Small intestine and Submaxillay gland, and the biggest uptake of 125 I-EGCG in there organs was 15.92, 5.83 and 11.56 %ID · g -1 respectively at 15 min post injection. In addition, 125 I-EGCG was cleared out from blood quickly, and the uptake of 131 I-EGCG in blood was 11.95 at 5 min, and decreased to 1.25 at 4 h post injection. Therefore, 125 I-EGCG was stable and it was metabolized mainly in Stomach, Small intestine, Submaxillay gland, worthy of further investigation to trace the compound in vivo and in vitro. (authors)

  8. The biodistribution of mouse monoclonal antibody ONS-M21 and the application for imaging diagnosis with its humanized antibody

    International Nuclear Information System (INIS)

    Ohkawa, Motohisa

    1997-01-01

    The mouse monoclonal antibody ONS-M21 combines with medulloblastomas and several gliomas specifically. And also we had already produced it humanized antibody. This study investigated the in vivo biodistribution of ONS-M21 and the application for imaging diagnosis using its humanized antibody. The nude mice (BALB/c nu/nu) bearing human medulloblastoma ONS-76 cells subcutaneously were injected 125 I-labeled ONS-M21 antibody via their tail vein. The radioactivities of their normal organs and the s.c. tumor were counted with γ-counter. And their autoradiograph (ARG) 6 hours after this administration was compared with gadolinium enhanced T1-weighted magnetic resonance image (Gd-T1-MRI). The brain tumor models transplanted ONS-76 cells stereotaxically was made by the nude rats (F344/N Jcl-rnu). And compared with MRI and ARG after the administration of 125 I-labeled humanized antibody into these models. The ARG indicated the accumulation of 125I -labeled ONS-M21 in the tumors which was detected by Gd-T1-MRI study. In this study, 125 I-labeled ONS-M21 remained in the tumor longer than the other normal organs. The mouse monoclonal antibody ONS-M21 have specific affinity for ONS-76 tumor in vivo. Then this humanized antibody is considerable to apply the imaging diagnosis of the malignant brain tumors. (author)

  9. Preparation and standardization of an 'in vitro' labelling methodology and study of [{sup 99m} Tc]-EDDA/Tricine/Hynic-[Tyr{sup 3}]-octreotide biodistribution; Preparacao e padronizacao de metodologia de marcacao 'in vitro' e estudo de biodistribuicao do octreotideo-[Tyr{sup 3} ]Hynic/EDDA/Tricina[{sup 99m}Tc

    Energy Technology Data Exchange (ETDEWEB)

    Hernandes Melero, Laura Terumi Ueda

    2008-07-01

    .60 {+-} 0.35 % at 5 hours using 80 /{mu}g octreotide-HYNIC, 10 mg of EDDA, 20 mg of tricine, 150 {mu}g of SnCI{sub 2}.2H{sub 2}0 in a final pH 8.0, and activity up to 3700 MBq (100 mCi). This formulation can be an alternative for the administration of more than one patient per labeling procedure, using a lyophilized reagent. The biodistribution performed by invasive method in the intervals of 1.5 and 4 hours after intravenous administration of the radiopharmaceutical in Swiss mice determined the percentage of the activity administered in the blood and the various organs. The biodistribution data in Swiss and Nude mice bearing AR42J tumor (rat pancreatic adenocarcinoma) were compatible with the distribution of the labeled peptide: fast blood clearance, high uptake in the kidneys due to the elimination by the urinary tract, and high uptake in organs with high density of somatostatin receptors like lung, stomach, pancreas and tumor in the case of Nude mice. The uptake of the radiolabeled peptide in the abdominal region was not significant and represents an advantage related to the diagnosis of neuroendocrine tumors, frequently found in this region. The labeling and biodistribution results described in this study showed the potential of the {sup 99m}Tc-labeled peptide to be applied in diagnostic procedures in nuclear medicine. (author)

  10. Synthesis, radiochromatography and biodistribution of Tc99m-hexakis-(methoxyisonitrile)-technetium(I) complexes

    International Nuclear Information System (INIS)

    Angelberger, P.; Zbiral, E.

    1987-09-01

    Following previous experience with Tc-99m-hexakis(t-butyl-isonitrile)-technetium(I) (Tc99m-tBiN) synthetic routes to the new ligands a) 1-methoxypropyl-2-isonitrile (MPiN) and b) 2-methoxy-2-methylpropyl-1-isonitrile(MiBiN) were developed via dehydration of the corresponding formamides. Formamide (a) was prepared from the available amine (a) while formamide (b) was synthesised by a difficult 5 step sequence starting from tert.2,2,2-trichlorobutanol. Product MPiN and MiBiN was purified by vacuum distillation and characterized by elemental analysis, IR- and NMR-spectra. A labeling method was developed based on earlier work with Tc99m-tBiN :the pure isonitrile ligand in ethanolic/aqueous solution was complexed at elevated temperature with reduced Tc-99m formed in situ with dithionite at alkaline pH. The whole reaction mixture was subjected to preparative HPLC leading to identification by UV-absorption and isolation of pure n.c.a. Tc99m-MPiN (A) and Tc99m-MiBiN (B) free of unreacted ligand. Work-up of the isolated peak resulted in an injectable product (overall radiochemical yield ∼80% within ∼40 min total preparation time) which was further controlled by TLC (radiochemical purity >97%, in vitro stability >6 hrs). Biodistribution in mice compared to identical data obtained with Tc99m-tBiN revealed somewhat higher heart uptake, slightly lower lung but significantly lower liver activity and renders these new Tc99m-compounds highly promising for myocardinal perfusion studies in man. 11 refs., 5 figs. (Author)

  11. Comparative studies of groundwater vulnerability assessment

    Science.gov (United States)

    Maria, Rizka

    2018-02-01

    Pollution of groundwater is a primary issue because aquifers are susceptible to contamination from land use and anthropogenic impacts. Groundwater susceptibility is intrinsic and specific. Intrinsic vulnerability refers to an aquifer that is susceptible to pollution and to the geological and hydrogeological features. Vulnerability assessment is an essential step in assessing groundwater contamination. This approach provides a visual analysis for helping planners and decision makers to achieve the sustainable management of water resources. Comparative studies are applying different methodologies to result in the basic evaluation of the groundwater vulnerability. Based on the comparison of methods, there are several advantages and disadvantages. SI can be overlaid on DRASTIC and Pesticide DRASTIC to extract the divergence in sensitivity. DRASTIC identifies low susceptibility and underestimates the pollution risk while Pesticide DRASTIC and SI represents better risk and is recommended for the future. SINTACS method generates very high vulnerability zones with surface waters and aquifer interactions. GOD method could be adequate for vulnerability mapping in karstified carbonate aquifers at small-moderate scales, and EPIK method can be used for large scale. GOD method is suitable for designing large area such as land management while DRASTIC has good accuracy and more real use in geoenvironmental detailed studies.

  12. Biodistribution and radiation dosimetry of the {alpha}{sub 7} nicotinic acetylcholine receptor ligand [{sup 11}C]CHIBA-1001 in humans

    Energy Technology Data Exchange (ETDEWEB)

    Sakata, Muneyuki [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1 Naka-cho, Itabashi-ku, Tokyo 173-0022 (Japan); Wu, Jin; Toyohara, Jun [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1 Naka-cho, Itabashi-ku, Tokyo 173-0022 (Japan); Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan); Oda, Keiichi [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1 Naka-cho, Itabashi-ku, Tokyo 173-0022 (Japan); Ishikawa, Masatomo [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1 Naka-cho, Itabashi-ku, Tokyo 173-0022 (Japan); Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan); Ishii, Kenji [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1 Naka-cho, Itabashi-ku, Tokyo 173-0022 (Japan); Hashimoto, Kenji [Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670 (Japan); Ishiwata, Kiichi, E-mail: ishiwata@pet.tmig.or.j [Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1 Naka-cho, Itabashi-ku, Tokyo 173-0022 (Japan)

    2011-04-15

    Introduction: 4-[{sup 11}C]Methylphenyl 2,4-diazabicyclo[3.2.2]nonane-2-carboxylate ([{sup 11}C]CHIBA-1001) is a newly developed positron emission tomography (PET) ligand for mapping {alpha}{sub 7} nicotinic acetylcholine receptors. We investigated whole-body biodistribution and radiation dosimetry of [{sup 11}C]CHIBA-1001 in humans and compared the results with those obtained in mice. Methods: Dynamic whole-body PET was carried out for three human subjects after administering a bolus injection of [{sup 11}C]CHIBA-1001. Emission scans were collected in two-dimensional mode over five bed positions. Regions of interest were placed over 12 organs. Radiation dosimetry was estimated from the residence times of these source organs using the OLINDA program. Biodistribution data from mice were also used for the prediction of radiation dosimetry in humans, and results with and those without accommodation of different proportions of organ-to-total-body mass were compared with the results from the human PET study. Results: In humans, the highest accumulation was observed in the liver, whereas in mice, the highest accumulation was observed in the urinary bladder. The estimated effective dose from the human PET study was 6.9 {mu}Sv/MBq, and that from mice was much underestimated. Conclusion: Effective dose estimates for [{sup 11}C]CHIBA-1001 were compatible with those associated with other common nuclear medicine tests. Absorption doses among several organs were considerably different between the human and mouse studies. Human dosimetry studies for the investigation of radiation safety are desirable as one of the first clinical trials of new PET probes before their application in subsequent clinical investigations.

  13. Proteomic Analysis of Serum Opsonins Impacting Biodistribution and Cellular Association of Porous Silicon Microparticles

    Directory of Open Access Journals (Sweden)

    Rita E. Serda

    2011-01-01

    Full Text Available Mass transport of drug delivery vehicles is guided by particle properties, such as size, shape, composition, and surface chemistry, as well as biomolecules and serum proteins that adsorb to the particle surface. In an attempt to identify serum proteins influencing cellular associations and biodistribution of intravascularly injected particles, we used two-dimensional gel electrophoresis and mass spectrometry to identify proteins eluted from the surface of cationic and anionic silicon microparticles. Cationic microparticles displayed a 25-fold greater abundance of Ig light variable chain, fibrinogen, and complement component 1 compared to their anionic counterparts. Anionic microparticles were found to accumulate in equal abundance in murine liver and spleen, whereas cationic microparticles showed preferential accumulation in the spleen. Immunohistochemistry supported macrophage uptake of both anionic and cationic microparticles in the liver, as well as evidence of association of cationic microparticles with hepatic endothelial cells. Furthermore, scanning electron micrographs supported cellular competition for cationic microparticles by endothelial cells and macrophages. Despite high macrophage content in the lungs and tumor, microparticle uptake by these cells was minimal, supporting differences in the repertoire of surface receptors expressed by tissue-specific macrophages. In summary, particle surface chemistry drives selective binding of serum components impacting cellular interactions and biodistribution.

  14. Proteomic Analysis of Serum Opsonins Impacting Biodistribution and Cellular Association of Porous Silicon Microparticles

    Science.gov (United States)

    Serda, Rita E.; Blanco, Elvin; Mack, Aaron; Stafford, Susan J.; Amra, Sarah; Li, Qingpo; van de Ven, Anne L.; Tanaka, Takemi; Torchilin, Vladimir P.; Wiktorowicz, John E.; Ferrari, Mauro

    2014-01-01

    Mass transport of drug delivery vehicles is guided by particle properties, such as shape, composition and surface chemistry, as well as biomolecules and serum proteins that adsorb to the particle surface. In an attempt to identify serum proteins influencing cellular associations and biodistribution of intravascularly injected particles, we used two dimensional gel electrophoresis and mass spectrometry to identify proteins eluted from the surface of cationic and anionic silicon microparticles. Cationic microparticles displayed a 25-fold greater abundance of Ig light chain variable region, fibrinogen, and complement component 1 compared to their anionic counterparts. The anionic-surface favored equal accumulation of microparticles in the liver and spleen, while cationic-surfaces favored preferential accumulation in the spleen. Immunohistochemistry supported macrophage internalization of both anionic and cationic silicon microparticles in the liver, as well as evidence of association of cationic microparticles with hepatic endothelial cells. Furthermore, scanning electron micrographs supported cellular competition for cationic microparticles by endothelial cells and macrophages. Despite high macrophage content in the lungs and tumor, microparticle uptake by these cells was minimal, supporting differences in the repertoire of surface receptors expressed by tissue-specific macrophages. In summary, particle surface chemistry drives selective binding of serum components impacting cellular interactions and biodistribution. PMID:21303614

  15. Pharmacokinetics of internally labeled monoclonal antibodies as a gold standard: comparison of biodistribution of 75Se-, 111In-, and 125I-labeled monoclonal antibodies in osteogenic sarcoma xenografts in nude mice

    International Nuclear Information System (INIS)

    Koizumi, M.; Endo, K.; Watanabe, Y.; Saga, T.; Sakahara, H.; Konishi, J.; Yamamuro, T.; Toyama, S.

    1989-01-01

    In order to know the true biodistribution of anti-tumor monoclonal antibodies, three monoclonal antibodies (OST6, OST7, and OST15) against human osteosarcoma and control antibody were internally labeled with 75Se by incubating [75Se]methionine and hybridoma cells. 75Se-labeled monoclonal antibodies were evaluated both in vitro and in vivo using the human osteogenic sarcoma cell line KT005, and the results were compared with those of 125I- and 111In-labeled antibodies. 75Se-, 125I- and 111In-labeled monoclonal antibodies had identical binding activities to KT005 cells, and the immunoreactivity was in the decreasing order of OST6, OST7, and OST15. On the contrary, in vivo tumor uptake (% injected dose/g) of 75Se- and 125I-labeled antibodies assessed using nude mice bearing human osteosarcoma KT005 was in the order of OST7, OST6, and OST15. In the case of 111In, the order was OST6, OST7, and OST15. High liver uptake was similarly seen with 75Se- and 111In-labeled antibodies, whereas 125I-labeled antibodies showed the lowest tumor and liver uptake. These data indicate that tumor targeting of antibody conjugates are not always predictable from cell binding studies due to the difference of blood clearance of labeled antibodies. Furthermore, biodistribution of both 111In- and 125I-labeled antibodies are not identical with internally labeled antibody. Admitting that internally labeled antibody is a ''gold standard'' of biodistribution of monoclonal antibody, high liver uptake of 111In-radiolabeled antibodies may be inherent to antibodies. Little, if any, increase in tumor-to-normal tissue ratios of antibody conjugates will be expected compared to those of 111In-labeled antibodies if stably coupled conjugates are administered i.v

  16. Comparative economic analysis: Anaerobic digester case study

    International Nuclear Information System (INIS)

    Lusk, P.D.

    1991-01-01

    An economic guide is developed to assess the value of anaerobic digesters used on dairy farms. Two varieties of anaerobic digesters, a conventional mixed-tank mesophilic and an innovative earthen psychrophilic, are comparatively evaluated using a cost-effectiveness index. The two case study examples are also evaluated using three other investment merit statistics: simple payback period, net present value, and internal rate of return. Life-cycle savings are estimated for both varieties, with sensitivities considered for investment risk. The conclusion is that an earthen psychrophilic digester can have a significant economic advantage over a mixed-tank mesophilic digester because of lower capital cost and reduced operation and maintenance expenses. Because of this economic advantage, additional projects are being conducted in North Carolina to increase the rate of biogas utilization. The initial step includes using biogas for milk cooling at the dairy farm where the existing psychrophilic digester is located. Further, a new project is being initiated for electricity production with thermal reclaim at a swine operation

  17. Comparative studies of stellarator and tokamak transport

    Energy Technology Data Exchange (ETDEWEB)

    Stroth, U; Burhenn, R; Geiger, J; Giannone, L.; Hartfuss, H J; Kuehner, G; Ledl, L; Simmet, E E; Walter, H [Max-Planck-Inst. fuer Plasmaphysik, IPP-Euratom Association, Garching (Germany); ECRH Team; W7-AS Team

    1997-09-01

    Transport properties in the W7-AS stellarator and in tokamaks are compared. The parameter dependences and the absolute values of the energy confinement time are similar. Indications are found that the density dependence, which is usually observed in stellarator confinement, can vanish above a critical density. The density dependence in stellarators seems to be similar to that in the linear ohmic confinement regime, which, in small tokamaks, extends to high density values, too. Because of the similarity in the gross confinement properties, transport in stellarators and tokamaks should not be dominated by the parameters which are very different in the two concepts, i.e. magnetic shear, major rational values of the rotational transform and plasma current. A difference in confinement is that there exists evidence for pinches in the particle and, possibly, energy transport channels in tokamaks whereas in stellarators no pinches have been observed, so far. In order to study the effect of plasma current and toroidal electric fields, stellarator discharges were carried out with an increasing amount of plasma current. From these experiments, no clear evidence of a connection of pinches with these parameters is found. The transient response in W7-AS plasmas can be described in terms of a non-local model. As in tokamaks, also cold pulse experiments in W7-AS indicate the importance of non-local transport. (author). 8 refs, 5 figs.

  18. COMPARATIVE STUDY ON ACCOUNTING AND FISCAL AMORTIZATION

    Directory of Open Access Journals (Sweden)

    MARIANA GURAU

    2012-05-01

    Full Text Available Placed in the international trend, Romanian accounting had experienced various changes, especially as regards of progress on disconnection between accounting and fiscality. In the present, fiscal rules should not have any role in accounting decisions, because accounting rules are applied to produce accounting information that is useful in making decisions and to provide a "true and fair view" upon financial reality of the entity. However, the barrier in the habit of accounting to thinking for fiscal point of view all economic transactions remains insurmountable, yet. Starting from this perspective on disconnection between accounting and fiscality would mean that amortization recorded in the accounting, as a result of management policy, to be different from fiscality amortization, to calculate income tax. Although formally accepted, disconnect between accounting and fiscality continues to meet many difficulties. In this sense, it is usual in practice to use the same method of amortization for accounting purposes and for fiscal purposes to prevent complications of double track amortization and prevent wandering in the rules in this field. Accounting rule is deliberately eluded in favor of the fiscal rules. This is the reason we proposed to make in this paper a comparative study between norms and rules on accounting and fiscal amortization, paper in which we intend to show the benefits of applying accounting and fiscal rules separately.

  19. Comparative study on Charpy specimen reconstitution techniques

    International Nuclear Information System (INIS)

    Bourdiliau, B.; Decroix, G.-M.; Averty, X.; Wident, P.; Bienvenu, Y.

    2011-01-01

    Highlights: → Welding processes are used to reconstitute previously tested Charpy specimens. → Stud welding is preferred for a quick installation, almost immediately operational. → Friction welding produces better quality welds, but requires a development effort. - Abstract: Reconstitution techniques are often used to allow material from previously fractured Charpy-V specimens to be reused for additional experiments. This paper presents a comparative experimental study of various reconstitution techniques and evaluates the feasibility of these methods for future use in shielded cells. The following techniques were investigated: arc stud welding, 6.0 kW CO 2 continuous wave laser welding, 4.5 kW YAG continuous wave laser welding and friction welding. Subsize Charpy specimens were reconstituted using a 400 W YAG pulsed wave laser. The best result was obtained with arc stud welding; the resilience of the reconstituted specimens and the load-displacement curves agreed well with the reference specimens, and the temperature elevation caused by the welding process was limited to the vicinity of the weld. Good results were also obtained with friction welding; this process led to the best quality welds. Laser welding seems to have affected the central part of the specimens, thus leading to different resilience values and load-displacement curves.

  20. A Comparative Study of Human Saposins

    Directory of Open Access Journals (Sweden)

    María Garrido-Arandia

    2018-02-01

    Full Text Available Saposins are small proteins implicated in trafficking and loading of lipids onto Cluster of Differentiation 1 (CD1 receptor proteins that in turn present lipid antigens to T cells and a variety of T-cell receptors, thus playing a crucial role in innate and adaptive immune responses in humans. Despite their low sequence identity, the four types of human saposins share a similar folding pattern consisting of four helices linked by three conserved disulfide bridges. However, their lipid-binding abilities as well as their activities in extracting, transporting and loading onto CD1 molecules a variety of sphingo- and phospholipids in biological membranes display two striking characteristics: a strong pH-dependence and a structural change between a compact, closed conformation and an open conformation. In this work, we present a comparative computational study of structural, electrostatic, and dynamic features of human saposins based upon their available experimental structures. By means of structural alignments, surface analyses, calculation of pH-dependent protonation states, Poisson-Boltzmann electrostatic potentials, and molecular dynamics simulations at three pH values representative of biological media where saposins fulfill their function, our results shed light into their intrinsic features. The similarities and differences in this class of proteins depend on tiny variations of local structural details that allow saposins to be key players in triggering responses in the human immune system.

  1. Assays for mammalian tyrosinase: a comparative study

    International Nuclear Information System (INIS)

    Jara, J.R.; Solano, F.; Lozano, J.A.

    1988-01-01

    This work describes a comparative study of the tyrosinase activity determined using three methods which are the most extensively employed; two radiometric assays using L-tyrosine as substrate (tyrosine hydroxylase and melanin formation activities) and one spectrophotometric assay using L-dopa (dopa oxidase activity). The three methods were simultaneously employed to measure the activities of the soluble, melanosomal, and microsomal tyrosinase isozymes from Harding-Passey mouse melanoma through their purification processes. The aim of this study was to find any correlation among the tyrosinase activities measured by the three different assays and to determine whether that correlation varied with the isozyme and its degree of purification. The results show that mammalian tyrosinase has a greater turnover number for L-dopa than for L-tyrosine. Thus, enzyme activity, expressed as mumol of substrate transformed per min, is higher in assays using L-dopa as substrate than those using L-tyrosine. Moreover, the percentage of hydroxylated L-tyrosine that is converted into melanin is low and is affected by several factors, apparently decreasing the tyrosinase activity measured by the melanin formation assay. Bearing these considerations in mind, average interassay factors are proposed. Their values are 10 to transform melanin formation into tyrosine hydroxylase activity, 100 to transform tyrosine hydroxylase into dopa oxidase activity, and 1,000 to transform melanin formation into dopa oxidase activity. Variations in these values due to the presence in the tyrosinase preparations of either inhibitors or regulatory factors in melanogenesis independent of tyrosinase are also discussed

  2. Radiolabeling and biodistribution of 62Cu-dithiocarbamate

    International Nuclear Information System (INIS)

    Matsumoto, Kazuya; Fujibayashi, Yasuhisa; Yokoyama, Akira; Konishi, Junji.

    1990-01-01

    The newly developed 62 Zn/ 62 Cu generator system has made available the production of the short-lived 62 Cu (T 1/2 = 9.8 min) positron radionuclide, eluted as 62 Cu-glycine. In the search for 62 Cu labeled radiopharmaceuticals for positron CT (PET) brain diagnostic studies, two ligands N,N-diethyl- and N,N-dimethyl-dithiocarbamic acid (DDC and DmDC) were selected, based on their Cu chelating abilities and the neutral lipophilic character of their copper chelates. In the present work, an in vitro study with non-radioactive Cu-glycine showed that both ligands easily formed the stable, neutral Cu-DDC and Cu-DmDC chelates (1:2 metal-ligand complexes) based on the ligand exchange reaction. Then the 62 Zn/ 62 Cu generator eluate, the 62 Cu-glycine was used for the radiolabeling of DDC and DmDC. The following HPLC analysis revealed that the ligand exchange reaction proceeded rapidly; the radiochemical purities of 62 Cu-DDC and 62 Cu-DmDC were extremely high (non-detectable 62 Cu-glycine) and both chelates were more lipophilic than 62 Cu-glycine. The mouse biodistribution of both radiolabeled compounds, 62 Cu-DDC and 62 Cu-DmDC indicated a brain accumlation of 2.8 and 5.3 times higher than 62 Cu-glycine, 15 min post injection, respectively. The brain accumulation observed with both 62 Cu-DDC and 62 Cu-DmDC might be due to their stable, neutral and lipophilic character; the latter enhanced by the presence of the methylated side chains. The gathered results indicated the applicability of dithiocarbamic acid derivatives in the production of new 62 Cu-labeled compounds using the 62 Zn/ 62 Cu generator system based on the ligand exchange reaction with 62 Cu-glycine eluate. Further studies with Cu-dithiocarbamic acid derivatives for development of new generator-produced 62 Cu positron radiopharmaceuticals can be recalled. (author)

  3. Effect of iron deficiency anemia on the biodistribution of {sup 99m}Tc radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Calmanovici, Gabriela P. [Radioisotopes Laboratory, Physics Department, School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956 - 1113, Buenos Aires (Argentina); Salgueiro, Maria J. [Radioisotopes Laboratory, Physics Department, School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956 - 1113, Buenos Aires (Argentina); Janjetic, Mariana A. [Physics Department, School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956 - 1113, Buenos Aires (Argentina); Leonardi, Natalia M. [Radioisotopes Laboratory, Physics Department, School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956 - 1113, Buenos Aires (Argentina); Boccio, Jose R. [Physics Department, School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956 - 1113, Buenos Aires (Argentina); Zubillaga, Marcela B. [Radioisotopes Laboratory, Physics Department, School of Pharmacy and Biochemistry, University of Buenos Aires, Junin 956 - 1113, Buenos Aires (Argentina)]. E-mail: mzubi@ffyb.uba.ar

    2006-05-15

    The distribution of colloids and labeled cells in organs is influenced by their intrinsic properties and by the state of the investigated subject. Iron deficiency remains an unsolved nutritional problem all over the world; one of its severe consequences is anemia. Because iron metabolism principally takes place in the liver, spleen, bone marrow, skeletal muscle and blood, we studied the effect of iron deficiency anemia on the biodistribution of {sup 99m}Tc phytate, {sup 99m}Tc gelatin colloid and {sup 99m}Tc RBC (red blood cells labeled with {sup 99m}Tc). Our results show that iron deficiency anemia modifies the pattern of biodistribution of the two colloids assayed. However, this behavior is different for both of them. This work contributes to studies that kinetically and statistically establish that iron deficiency anemia induces a significant inversion in the spleen-liver activity relationship when centellographic studies are performed with colloids such as {sup 99m}Tc phytate.

  4. 99mTc-glycopeptide: Synthesis, biodistribution and imaging in breast tumor-bearing rodents

    International Nuclear Information System (INIS)

    Wei, I-C.; Tsao Ning; Huang Yahui; Ho Yensheng; Wu Chungchin; Yu Dongfang; Yang, David J.

    2008-01-01

    This study was aimed to develop a glycopeptide (GP) to be used as a carrier for anti-cancer drug delivery. GP was synthesized by conjugating glutamate peptide and chitosan using carbodiimide as a coupling agent. Elemental analysis and capillary electrophoresis confirmed the purity was >95%. GP was labeled with sodium pertechnetate (Na 99m TcO 4 ) for in vitro and in vivo studies. Rhenium-GP was synthesized to support the binding site of 99m Tc at the glutamate positions 3-5. In vitro cellular uptake of 99m Tc-GP was performed in breast cancer cells. Cytosol had 60% whereas nucleus had 40% uptake of 99m Tc-GP. When cancer cells were incubated with glutamate or aspartate, followed by 99m Tc-GP, there was decreased uptake in cells treated with glutamate but not aspartate. The findings indicated that cellular uptake of 99m Tc-GP was via glutamate transporters. In addition, 99m Tc-GP was able to measure uptake differences after cells treated with paclitaxel. Biodistribution and planar imaging were conducted in breast tumor-bearing rats. Biodistribution of 99m Tc-GP showed increased tumor-to-tissue ratios as a function of time. Planar images confirmed that 99m Tc-GP could assess tumor uptake changes after paclitaxel treatment. In vitro and in vivo studies indicated that GP could target tumor cells, thus, GP may be a useful carrier for anti-cancer drug delivery

  5. Differential biodistribution of oncolytic poxvirus administered systemically in an autochthonous model of hepatocellular carcinoma.

    Science.gov (United States)

    Baril, Patrick; Touchefeu, Yann; Cany, Jeannette; Cherel, Yan; Thorne, Steve H; Tran, Lucile; Conchon, Sophie; Vassaux, Georges

    2011-12-01

    Preclinical studies have demonstrated that, unlike oncolytic adenoviruses, oncolytic vaccinia viruses can reach implanted tumors upon systemic injection. However, the biodistribution of this oncolytic agent in in situ autochthonous tumor models remains poorly characterized. In the present study, we assessed this biodistribution in a model of mouse hepatocellular carcinoma (HCC) obtained after injection of the carcinogen diethylnitrosamine (DEN). Twelve months after DEN administration, histology, quantitative reverse transcription-polymerase chain reaction, in situ hybridization and viral titration were used to characterize tumors, as well as to assess the viral load of the livers upon either intravenous or intraperitoineal injection. The results obtained showed that the architecture of the liver was lost, with a noticeable absence of sinusoids, as well as the presence of steatosis and α-fetoprotein-positive HCC tumor nodules. Bioluminescence imaging and measures of the infective virus load demonstrated that intravenous injection of 10(8)  plaque-forming units of the recombinant vaccinia virus led to a predominant transduction of the liver, whereas intraperitoneal injection resulted in a lower level of liver transduction accompanied by an increased infection of the lungs, spleen, kidneys and bowels. Immunohistochemical analysis of liver sections of animals injected intravenously with the virus revealed a preferential localization of vaccinia-specific immunoreactivity in the tumors. The findings of the present study emphasize the importance of the route of administration of the vector and highlight the relevance of systemic injection of oncolytic vaccinia virus in the context of hepatocellular carcinoma. Copyright © 2011 John Wiley & Sons, Ltd.

  6. Comparison of cell uptake, biodistribution and tumor retention of folate-coated and PEG-coated gadolinium nanoparticles in tumor-bearing mice.

    Science.gov (United States)

    Oyewumi, Moses O; Yokel, Robert A; Jay, Michael; Coakley, Tricia; Mumper, Russell J

    2004-03-24

    The purpose of these studies was to compare the cell uptake, biodistribution and tumor retention of folate-coated and PEG-coated gadolinium (Gd) nanoparticles. Gd is a potential agent for neutron capture therapy (NCT) of tumors. Gd nanoparticles were engineered from oil-in-water microemulsion templates. To obtain folate-coated nanoparticles, a folate ligand [folic acid chemically linked to distearoylphosphatidylethanolamine (DSPE) via a PEG spacer MW 3350] was included in nanoparticle preparations. Similarly, control nanoparticles were coated with DSPE-PEG-MW 3350 (PEG-coated). Nanoparticles were characterized based on size, size distribution, morphology, biocompatibility and tumor cell uptake. In vivo studies were carried out in KB (human nasopharyngeal carcinoma) tumor-bearing athymic mice. Biodistribution and tumor retention studies were carried out at pre-determined time intervals after injection of nanoparticles (10 mg/kg). Gd nanoparticles did not aggregate platelets or activate neutrophils. The retention of nanoparticles in the blood 8, 16 and 24 h post-injection was 60%, 13% and 11% of the injected dose (ID), respectively. A maximum Gd tumor localization of 33+/-7 microg Gd/g was achieved. Both folate-coated and PEG-coated nanoparticles had comparable tumor accumulation. However, the cell uptake and tumor retention of folate-coated nanoparticles was significantly enhanced over PEG-coated nanoparticles. Thus, the benefits of folate ligand coating were to facilitate tumor cell internalization and retention of Gd-nanoparticles in the tumor tissue. The engineered nanoparticles may have potential in tumor-targeted delivery of Gd thereby enhancing the therapeutic success of NCT.

  7. Biodistribution of nanoparticles of hydrophobic gadopentetic-acid derivative prepared with a planetary ball mill for neutron-capture therapy of cancer

    International Nuclear Information System (INIS)

    Nabeta, Chika; Ichikawa, Hideki; Fukumori, Yoshinobu

    2006-01-01

    Nanoparticles of hydrophobic gadopentetic-acid derivatives (Gd-nanoGR) were prepared with a wet ball-milling process for gadolinium neutron-capture therapy. Ball-milling of solid mass of gadopentetic acid distearylamide with soybean lecithin as a dispersant in the presence of water and subsequent sonication at 70degC resulted in the Gd-nanoGR with the particle size of 63 nm. Biodistribution study using melanoma-bearing hamsters demonstrated that the i.v. injection of the Gd-nanoGR made a higher gadolinium accumulation in tumor (109 μg Gd/g wet tumor at 6h after administration), when compared with the gadolinium-loaded micellar-like nanoparticles previously reported. (author)

  8. 123I and131I labelled p-iodophenylpentadecanoic acid (p-IPPA): simplified preparation. Biodistribution in mice, rabbits and patients

    International Nuclear Information System (INIS)

    Angelberger, P.; Wagner-Loeffler, M.; Hruby, R.; Dudczak, R.; Schmoliner, R.; Kletter, K.; Frischauf, H.

    1981-01-01

    In an attempt to avoid the second injection of radioiodide as an internal standard for catabolically released iodide, Machulla et al proposed 15-phenyl-penta-decanoic acid (PPA), labelled at the phenyl ring, for myocardial imaging and metabolic studies. PPA is catabolized via β-oxidation to benzoic acid which is known to be rapidly excreted as hippuric acid. After labelling, three sequential HPLC separations were recommended to purify the labelled p-Isomer (p-IPPA). In this process three intermediate evaporation steps have also to be performed. Thus it seems important to look for improved purification procedures which may possibly reduce the preparation time. The present report compares different purification procedures and relates them to the biodistribution of the final product in mice and rabbits. (Auth.)

  9. I-124 production using nanomaterials and its biodistribution in animals

    International Nuclear Information System (INIS)

    Braghirolli, Ana Maria Silveira

    2014-01-01

    Iodine-124 is a positron emitter with physical half-life of 4.2 days. Its decay occurs by positron emission (23.3%) and electron capture (76.7%). Their physical and chemical characteristics make it an attractive isotope for medical applications. The development of new imaging techniques, improvements in Positron Emission Tomography (PET), the development of new detectors and computational methods of signal processing, open new perspectives for its application. The increasing use of PET technology in medical oncology, pharmacokinetics and drug metabolism, make the radiopharmaceuticals labeled with 124 I a tool of great interest and usefulness. The use of 124 I - labeled molecules stands out particularly due to the convenient half-life of 124 I. This feature enables diagnostic imaging in PET centers far away from the radionuclides producing center. Within this context, this work presents a method for the production and separation of 124 I. This method is innovative and pioneering in the country. It is based on the development and use of nanostructured targets of nat TeO 2 . These targets are irradiated in a charged particles accelerator, with variable energy, the IEN's CV-28 cyclotron. The irradiations are performed with 24 MeV, initial energy, proton beams. In the preparation of nanoparticulated targets the highlight was the simplicity of the method that uses the sol-gel technique for obtaining nanoparticles, TeCl 4 as precursor and water as solvent. The produced 124 I was separated from the target material by dry distillation and trapped in a NaOH solution (0.02 M), in an automated system. The thick target yield was 6.81 MBq/μAh, and the synthesis yield was 90%. The 124 I obtained was then used in preliminary biodistribution studies. These studies were performed on a micro PET, model Lab PET 4 of the CDTN, in Swiss type mice. The results of the application of Na 124 I showed high quality PET imaging of the thyroid, with the maximum uptake at 6 h after

  10. In vivo biodistribution of 131I labeled bleomycin (BLM) and isomers (A2 and B2) on experimental animal models

    International Nuclear Information System (INIS)

    Avcibasi, U.; Demiroglu, H.; Uenak, P.; Mueftueler, F.Z.B.; Ichedef, C.A.; Guemueser, F.G.

    2010-01-01

    Bleomycins (BLMs; BLM, A2, and B2) were labeled with 131 I and radiopharmaceutical potentials were investigated using animal models in this study. Quality control procedures were carried out using thin layer radiochromatography (TLRC), high performance liquid chromatography (HPLC), and liquid chromatography (LC/MS/MS). Labeling yields of radiolabeled BLMs were found to be 90, 68, and 71%, respectively. HPLC chromatograms were taken for BLM and cold iodinated BLM ( 127 I-BLM). Five peaks were detected for BLM and three peaks for 127 I-BLM in the HPLC studies. Two peaks belong to isomers of BLM. The isomers of BLM were purified with using HPLC. Biological activity of BLM was determined on male Albino Wistar rats by biodistribution and scintigraphic studies were performed for BLMs by using New Zealand rabbits. The biodistribution results of 131 I-BLM showed high uptake in the stomach, the bladder, the prostate, the testicle, and the spinal cord in rats. Scintigraphic results on rabbits agrees with that of biodistributional studies on rats. The scintigraphy of radiolabeled isomers ( 131 I-A2 and 131 I-B2) are similarly found with that of 131 I-BLM. (author)

  11. Biodistribution of the {sup 18}F-FPPRGD{sub 2} PET radiopharmaceutical in cancer patients: an atlas of SUV measurements

    Energy Technology Data Exchange (ETDEWEB)

    Minamimoto, Ryogo; Jamali, Mehran; Gambhir, Sanjiv Sam [Stanford University, Stanford, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford, CA (United States); Stanford University, Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford, CA (United States); Barkhodari, Amir; Mosci, Camila; Mittra, Erik; Iagaru, Andrei [Stanford University, Stanford, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford, CA (United States); Shen, Bin; Chin, Frederick [Stanford University, Molecular Imaging Program at Stanford (MIPS), Department of Radiology, Stanford, CA (United States)

    2015-11-15

    The aim of this study was to investigate the biodistribution of 2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid (RGD) peptide (PEG3-E[c{RGDyk}]2) ({sup 18}F-FPPRGD{sub 2}) in cancer patients and to compare its uptake in malignant lesions with {sup 18}F-FDG uptake. A total of 35 patients (11 men, 24 women, mean age 52.1 ± 10.8 years) were enrolled prospectively and had {sup 18}F-FPPRGD{sub 2} PET/CT prior to treatment. Maximum standardized uptake values (SUV{sub max}) and mean SUV (SUV{sub mean}) were measured in 23 normal tissues in each patient, as well as in known or suspected cancer lesions. Differences between {sup 18}F-FPPRGD{sub 2} uptake and {sup 18}F-FDG uptake were also evaluated in 28 of the 35 patients. Areas of high {sup 18}F-FPPRGD{sub 2} accumulation (SUV{sub max} range 8.9 - 94.4, SUV{sub mean} range 7.1 - 64.4) included the bladder and kidneys. Moderate uptake (SUV{sub max} range 2.1 - 6.3, SUV{sub mean} range 1.1 - 4.5) was found in the choroid plexus, salivary glands, thyroid, liver, spleen, pancreas, small bowel and skeleton. Compared with {sup 18}F-FDG, {sup 18}F-FPPRGD{sub 2} showed higher tumor-to-background ratio in brain lesions (13.4 ± 8.5 vs. 1.1 ± 0.5, P < 0.001), but no significant difference in body lesions (3.2 ± 1.9 vs. 4.4 ± 4.2, P = 0.10). There was no significant correlation between the uptake values (SUV{sub max} and SUV{sub mean}) for {sup 18}F FPPRGD{sub 2} and those for {sup 18}F-FDG. The biodistribution of {sup 18}F-FPPRGD{sub 2} in cancer patients is similar to that of other RGD dimer peptides and it is suitable for clinical use. The lack of significant correlation between {sup 18}F-FPPRGD{sub 2} and {sup 18}F-FDG uptake confirms that the information provided by each PET tracer is different. (orig.)

  12. Biodistribution of the 18F-FPPRGD2 PET radiopharmaceutical in cancer patients: an atlas of SUV measurements

    International Nuclear Information System (INIS)

    Minamimoto, Ryogo; Jamali, Mehran; Gambhir, Sanjiv Sam; Barkhodari, Amir; Mosci, Camila; Mittra, Erik; Iagaru, Andrei; Shen, Bin; Chin, Frederick

    2015-01-01

    The aim of this study was to investigate the biodistribution of 2-fluoropropionyl-labeled PEGylated dimeric arginine-glycine-aspartic acid (RGD) peptide (PEG3-E[c{RGDyk}]2) ( 18 F-FPPRGD 2 ) in cancer patients and to compare its uptake in malignant lesions with 18 F-FDG uptake. A total of 35 patients (11 men, 24 women, mean age 52.1 ± 10.8 years) were enrolled prospectively and had 18 F-FPPRGD 2 PET/CT prior to treatment. Maximum standardized uptake values (SUV max ) and mean SUV (SUV mean ) were measured in 23 normal tissues in each patient, as well as in known or suspected cancer lesions. Differences between 18 F-FPPRGD 2 uptake and 18 F-FDG uptake were also evaluated in 28 of the 35 patients. Areas of high 18 F-FPPRGD 2 accumulation (SUV max range 8.9 - 94.4, SUV mean range 7.1 - 64.4) included the bladder and kidneys. Moderate uptake (SUV max range 2.1 - 6.3, SUV mean range 1.1 - 4.5) was found in the choroid plexus, salivary glands, thyroid, liver, spleen, pancreas, small bowel and skeleton. Compared with 18 F-FDG, 18 F-FPPRGD 2 showed higher tumor-to-background ratio in brain lesions (13.4 ± 8.5 vs. 1.1 ± 0.5, P < 0.001), but no significant difference in body lesions (3.2 ± 1.9 vs. 4.4 ± 4.2, P = 0.10). There was no significant correlation between the uptake values (SUV max and SUV mean ) for 18 F FPPRGD 2 and those for 18 F-FDG. The biodistribution of 18 F-FPPRGD 2 in cancer patients is similar to that of other RGD dimer peptides and it is suitable for clinical use. The lack of significant correlation between 18 F-FPPRGD 2 and 18 F-FDG uptake confirms that the information provided by each PET tracer is different. (orig.)

  13. Radioiodination and biodistribution of isolated lawsone compound from Lawsonia inermis (henna) leaves extract

    International Nuclear Information System (INIS)

    Volkan Tekin; Zumrut Biber Muftuler, F.; Ayfer Yurt Kilcar; Perihan Unak

    2014-01-01

    Lawsonia inermis (henna) is one of the most effective medicinal plants and it has been using for treatment of wounds and burns for centuries. The using of Henna leaves is very popular for cosmetic as well as medicine in many countries. Henna leaves contain lots of different compounds and lawsone (LW) is the main one. In current study, extraction with bidistillated water of henna leaves was performed and LW was isolated by using high performance liquid chromatography system. Chemical structure of LW was evaluated by nuclear magnetic resonance method. LW was radiolabeled with iodine-131 ( 131 I) radionuclide which is well known for nuclear imaging and therapy in nuclear medicine by utilizing iodogen method. The yield of radiolabeling of LW ( 131 I-LW) was calculated as 92.70 ± 4.312 % (n = 10) by thin layer radio chromatography. Its in vivo biological activity was investigated by biodistribution studies which were performed by using healthy female and male Balb/C mice. According to results of biodistribution, uptake of 131 I labeled LW compound in uterus, breast and ovary for female mice and prostate in male mice was higher than other organs in the body. (author)

  14. In vivo evaluation of potential Tc-99m brain perfusion agents using brain uptake index determination and biodistribution

    International Nuclear Information System (INIS)

    Rajeckas, A.J.; Watson, A.D.; Subramanyam, V.; Williams, S.J.; Belonga, B.Q.; de Nemours, E.I.D.

    1985-01-01

    In order to evaluate the pharmacological properties of various Tc-99m complexes as potential brain perfusion agents, the authors have employed both biodistribution techniques as well as modified Oldendorf procedure for the determination of the brain uptake index (BUI). A typical BUI determination involves the coinjection of 1 microcurie each of I-125 iodoantipyrine and the Tc-99m complex into the left carotid artery of a pentabarbitol anesthetized rat. The animal is sacrificed at 10 seconds; the right and left hemispheres of the brain are removed and counted for each isotope in a gamma well counter. Biodistribution studies are performed using tail-vein injections in unanesthetized rats. In the evaluation of a series of Tc-99m N/sub 2/S/sub 2/ (diamine dithiol) complexes, they have observed that compounds with a low BUI (less than 50) also have a low brain concentration (less than 1% ID) at 30 seconds post injection

  15. Synthesis quality control and biodistribution of technetium-99m triamcinolone (99mTc-TA) complex: An inflammation tracer agent

    International Nuclear Information System (INIS)

    Rizvii, Faheem Askari; Naqvi, Syed Ali Raza; Mehdi, Muhammad; Roohi, Samina; Zahoor, Ameer Fawad; Khan, Zulfiqar Ali; Sohaib, Muhammad; Rasheed, Rashid

    2017-01-01

    In present study synthesis of 99m Tc-triamcinolone acetonide ( 99m Tc-TA) complex and its stability using set of quality control parameters such as ligand concentration, reducing agent concentration, pH, temperature and reaction time was assessed. 99m Tc-TA complex was characterized in terms of percent (%) yield, stability in saline and serum using chromatographic procedures. Radiochemically the 99m Tc-TA complex was found quite stable in saline and serum. After 30 min of reaction the complex showed maximum radiochemical yield of 96.32% which decreased to 96.25 % after 4 h incubation period. In serum, the % yield of radiochemical was remained same up to 2 h which decreased to 93.5% at 24 h time point. Normal biodistribution pattern in Sprague-Dawley rats revealed liver, stomach and kidneys as areas of high 99m Tc-TA complex uptake (8.44 ±1.32, 8.75 ± 1.03 and 12.67 ± 1.21%, respectively) at 1 h post injection time point. Scintigraphy of 99m Tc-TA in rabbits showed similar eco as observed in biodistribution study. Based on the promising results obtained in context of in vitro and in vivo stability and biodistribution, 99m Tc-TA complex could be further studied to identify the inflammation based diseases

  16. Nonclinical comparability studies of recombinant human arylsulfatase A addressing manufacturing process changes.

    Science.gov (United States)

    Wright, Teresa; Li, Aiqun; Lotterhand, Jason; Graham, Anne-Renee; Huang, Yan; Avila, Nancy; Pan, Jing

    2018-01-01

    Recombinant human arylsulfatase A (rhASA) is in clinical development for the treatment of patients with metachromatic leukodystrophy (MLD). Manufacturing process changes were introduced to improve robustness and efficiency, resulting in higher levels of mannose-6-phosphate and sialic acid in post-change (process B) compared with pre-change (process A) rhASA. A nonclinical comparability program was conducted to compare process A and process B rhASA. All doses were administered intrathecally. Pharmacodynamic comparability was evaluated in immunotolerant MLD mice, using immunohistochemical staining of lysosomal-associated membrane protein-1 (LAMP-1). Pharmacokinetic comparability was assessed in juvenile cynomolgus monkeys dosed once with 6.0 mg (equivalent to 100 mg/kg of brain weight) process A or process B rhASA. Biodistribution was compared by quantitative whole-body autoradiography in rats. Potential toxicity of process B rhASA was evaluated by repeated rhASA administration at doses of 18.6 mg in juvenile cynomolgus monkeys. The specific activities for process A and process B rhASA were 89 U/mg and 106 U/mg, respectively, which were both well within the target range for the assay. Pharmacodynamic assessments showed no statistically significant differences in LAMP-1 immunohistochemical staining in the spinal cord and in most of the brain areas assessed between process A and B rhASA-dosed mice. LAMP-1 staining was reduced with both process A and B rhASA compared with vehicle, supporting its activity. Concentration-time curves in cerebrospinal fluid and serum of cynomolgus monkeys were similar with process A and B rhASA. Process A and B rhASA were similar in terms of their pharmacokinetic parameters and biodistribution data. No process B rhASA-related toxicity was detected. In conclusion, manufacturing process changes did not affect the pharmacodynamic, pharmacokinetic or safety profiles of process B rhASA relative to process A rhASA.

  17. Preparation, quality control and biodistribution of [61Cu]-doxorubicin for PET imaging

    International Nuclear Information System (INIS)

    Jalilian, A.R.; Akhlaghi, M.; Zandi, H.; Yousefnia, H.; Faghihi, R.

    2009-01-01

    This work was conducted for radiolabeling of an anticancer antibiotic, i.e. doxorubicin with 61 Cu for production of possible tracer used in PET oncology. 61 Cu was prepared with natural zinc target and 22 MeV 150 μA protons via nat Zn(p, xn) 61 Cu reaction with a yield of 123.2 MBq·μA -1 ·h -1 . Optimization reactions were performed for pH, temperature and concentration. Biodistribution of the tracer was studied in normal and fibrosarcoma bearing mice. At the optimized conditions, ITLC showed that radiochemical purity was over 97% with a specific activity of 2.22 X 10 3 MBq·mmol -1 ·L -1 . This was kept unchanged even with presence of human serum as well as room temperature for 5 h. Biodistribution of the tracer in fibrosarcoma bearing mice demonstrated significant tumor uptake after 2 h. This tracer can be used in the detection of various tumors responding to doxorubicin chemotherapy using PET scan and/or determination of tumor therapy response to doxorubicin chemotherapy. (authors)

  18. Molecular Imaging of Stem Cells: Tracking Survival, Biodistribution, Tumorigenicity, and Immunogenicity

    Directory of Open Access Journals (Sweden)

    Eugene Gu, Wen-Yi Chen, Jay Gu, Paul Burridge, Joseph C. Wu

    2012-01-01

    Full Text Available Being able to self-renew and differentiate into virtually all cell types, both human embryonic stem cells (hESCs and induced pluripotent stem cells (iPSCs have exciting therapeutic implications for myocardial infarction, neurodegenerative disease, diabetes, and other disorders involving irreversible cell loss. However, stem cell biology remains incompletely understood despite significant advances in the field. Inefficient stem cell differentiation, difficulty in verifying successful delivery to the target organ, and problems with engraftment all hamper the transition from laboratory animal studies to human clinical trials. Although traditional histopathological techniques have been the primary approach for ex vivo analysis of stem cell behavior, these postmortem examinations are unable to further elucidate the underlying mechanisms in real time and in vivo. Fortunately, the advent of molecular imaging has led to unprecedented progress in understanding the fundamental behavior of stem cells, including their survival, biodistribution, immunogenicity, and tumorigenicity in the targeted tissues of interest. This review summarizes various molecular imaging technologies and how they have advanced the current understanding of stem cell survival, biodistribution, immunogenicity, and tumorigenicity.

  19. Biodistribution and catabolism of 18F-labelled isopeptide N(epsilon)-(gamma-glutamyl)-L-lysine.

    Science.gov (United States)

    Hultsch, C; Bergmann, R; Pawelke, B; Pietzsch, J; Wuest, F; Johannsen, B; Henle, T

    2005-12-01

    Isopeptide bonds between the epsilon-amino group of lysine and the gamma-carboxamide group of glutamine are formed during strong heating of pure proteins or, more important, by enzymatic reaction mediated by transglutaminases. Despite the wide use of a microbial transglutaminase in food biotechnology, up to now little is known about the metabolic fate of the isopeptide N(epsilon)-(gamma-glutamyl)-L-lysine. In the present study, N-succinimidyl-4-[(18)F]fluorobenzoate was used to modify N(epsilon)-(gamma-glutamyl)-L-lysine at each of its two alpha-amino groups, resulting in the 4-[(18)F]fluorobenzoylated derivatives, for which biodistribution, catabolism, and elimination were investigated in male Wistar rats. A significant different biochemical behavior of the two labelled isopeptides was observed in terms of in vitro stability, in vivo metabolism as well as biodistribution. The results suggest that the metabolic fate of isopeptides is likely to be dependent on how they are reabsorbed - free or peptide bound.

  20. Ciprofloxacin-99mTc: labeling and biodistribution in infection diagnostic

    International Nuclear Information System (INIS)

    Martins, Patricia de Andrade

    2004-01-01

    Labeling and biodistribution studies with the antibiotic ciprofloxacin were done using as radio marker Tc-99m. The aims were to optimize the labeling procedures as well as to analyze its efficacy in the diagnosis of infection sites, healthy and experimentally infected animals were employed to this purpose. On basis of optimized parameters a freeze-dried could be formulated containing 2 mg ciprofloxacin, 30 μg SnCl 2 H O and 5 mg ascorbic acid. This preparation could be easily activated by the addiction of Na 99m Tc) 4 a maximum value of 3700 MBq after a reaction time of 10 minutes only. Yield of the labeling technique higher than 95%, radiochemical stability reached 6 hours after preparation, and shelf life till 2 months was demonstrated. Biodistribution investigations revealed high renal excretion, low concentration in liver and soft tissues, along with affinity for the bacterial focus 1.7-2.4 times higher than for normal tissues. This protocol demonstrated the potential of ciprofloxacin- 99m Tcs a diagnostic agent for infections process. (author)

  1. Labelling and biodistribution of /sup 99m/Tc-ceftriaxone: a new imaging agent

    International Nuclear Information System (INIS)

    Khurshid, Z.; Roohi, S.; Zahoor, R.; Tariq, S.

    2012-01-01

    Most commonly used infection imaging agents are specific for inflammation. Some newer agents like labeled antimicrobials and peptides have shown infection seeking properties. Research is underway for synthesis of newer imaging agents specific for infections. In this quest we have labeled and bio evaluated /sup 99m/Tc-ceftriaxone. Ceftriaxone is a commonly used third generation cephalosporin antibiotic having a broad anti-bacterial spectrum but has more specificity for gram-negative bacteria. /sup 99m/Tc-ceftriaxone was prepared at ph 7 by adding 30 mg of ligand to /sup 99m/Tc in the presence of 50 mu g of SnCl/sub 2/./sup 2/H/sub 2/O. Boiling for ten minutes gave maximum labeling yield (96+1.76%). The stability at room temperature both with and without human serum was more than 90% till 24 hours. In-vitro binding revealed maximum binding of 68% and 47% with E.coli and S.aureus respectively after 4 hours incubation. Biodistribution studies in normal rats showed maximum uptake in hepatobiliary system followed by kidney. In infection and inflammation models the maximum target to non- target ratios of 12.66 +- 2.59, 2.36 +- 0.30 and 1.44 +- 0.53 were achieved with E. coli, S. aureus and oil inflammation respectively 4 hours post injection. Scintigraphic findings also correlated with biodistribution results. (Orig./A.B.)

  2. Platelet binding and biodistribution of [{sup 99m}Tc]rBitistatin in animal species and humans

    Energy Technology Data Exchange (ETDEWEB)

    Knight, Linda C. [Department of Radiology, Temple University School of Medicine, Philadelphia, PA 19140 (United States)], E-mail: lknight@temple.edu; Romano, Jan E. [Department of Radiology, Temple University School of Medicine, Philadelphia, PA 19140 (United States); Bright, Lewis T.; Agelan, Alexis [University Laboratory Animal Resources, Temple University School of Medicine, Philadelphia, PA 19140 (United States); Kantor, Steven; Maurer, Alan H. [Department of Radiology, Temple University School of Medicine, Philadelphia, PA 19140 (United States)

    2007-10-15

    Introduction: {sup 99m}Tc recombinant bitistatin (rBitistatin) is a radioligand for {alpha}{sub IIb}{beta}{sub 3} (glycoproteins IIb/IIIa) receptor on platelets and is being developed as a diagnostic radiopharmaceutical for in vivo imaging of acute thrombi and emboli. Prior to the first administration of [{sup 99m}Tc]rBitistatin to human subjects, its biodistribution and effects on platelets were evaluated in animals. This paper reports findings in animal studies in comparison with initial findings in normal human subjects. Methods: [{sup 99m}Tc]rBitistatin was administered to mice, guinea pigs and dogs to assess time-dependent organ distribution, urinary excretion and blood disappearance rates. Blood samples were analyzed to determine radioligand binding to circulating platelets and the extent of plasma protein binding. The effect of [{sup 99m}Tc]rBitistatin on circulating platelet count was determined. These factors were also determined in normal human subjects who received [{sup 99m}Tc]rBitistatin as part of a Phase I clinical trial. Results: The main organs that accumulated [{sup 99m}Tc]rBitistatin were kidneys, liver and spleen in all animal species and humans. The main organs seen on human images were the kidneys and spleen. Liver uptake was fainter, and soft-tissue background was low. [{sup 99m}Tc]rBitistatin bound to circulating platelets in blood, with a higher percentage of binding to platelets in guinea pigs and dogs compared to that in humans. Plasma protein binding was low and of little consequence in view of platelet binding. The main route of excretion was through the urine. [{sup 99m}Tc]rBitistatin did not affect platelet counts in humans or dogs. Conclusions: [{sup 99m}Tc]rBitistatin, when administered at low doses for imaging, has no adverse effects on platelets and has the qualitative biodistribution predicted by animal studies. [{sup 99m}Tc]rBitistatin was found to bind to circulating platelets in humans, suggesting that it will be able to bind

  3. Comparative Studies on Some Physicochemical Properties of ...

    African Journals Online (AJOL)

    Industrial and nutritional processes have increased the demands for oil and this in turn has led to the search for oils from different types of seeds. It is in this vein that baobab seed oil was extracted, analyzed and some of it physicochemical properties compared with those of vegetable, peanut and palm oils. The percentage ...

  4. A comparative study of fingerprint thinning algorithms

    CSIR Research Space (South Africa)

    Khanyile, NP

    2011-08-01

    Full Text Available are compared in terms of the quality of the skeletons they produce (i.e. connectivity and spurious branches) as well as the time complexity associated with each algorithm. Results show that faster algorithms have difficulty preserving connectivity. Zhang...

  5. Counseling in Costa Rica: A Comparative Study

    Science.gov (United States)

    Collier, Crystal

    2013-01-01

    With one of the world's most comprehensive universal healthcare systems, medical tourism in Costa Rica has increased significantly over the past few decades. American tourists save up to 80% of comparative costs for procedures, from heart surgery to root canal treatment. Although many Costa Rican healthcare professionals receive training in North…

  6. Calcaneal fracture classification: a comparative study

    NARCIS (Netherlands)

    Schepers, Tim; van Lieshout, Esther M. M.; Ginai, Abida Z.; Mulder, Paul G. H.; Heetveld, Martin J.; Patka, Peter

    2009-01-01

    Comparing different types of calcaneal fractures, associated treatment options, and outcome data is currently hampered by the lack of consensus regarding fracture classification. A systematic search for articles dealing with calcaneal fracture was performed, and the prevalence of use of each

  7. The Teaching of Anthropology: A Comparative Study.

    Science.gov (United States)

    Lombard, Jacques

    1984-01-01

    College-level anthropology teaching in various countries, including Belgium, France, Germany, the Netherlands, Portugal, South Africa, the United Kingdom, and Yugoslavia, is compared. Terminology is examined and historical background is provided. Also discussed are educational crises, the organization of teaching, and teaching methods. (RM)

  8. Monitoring of Biodistribution and Persistence of Conditionally Replicative Adenovirus in a Murine Model of Ovarian Cancer Using Capsid-Incorporated mCherry and Expression of Human Somatostatin Receptor Subtype 2 Gene

    Directory of Open Access Journals (Sweden)

    Igor P. Dmitriev

    2014-10-01

    Full Text Available A significant limiting factor to the human clinical application of conditionally replicative adenovirus (CRAd-based virotherapy is the inability to noninvasively monitor these agents and their potential persistence. To address this issue, we proposed a novel imaging approach that combines transient expression of the human somatostatin receptor (SSTR subtype 2 reporter gene with genetic labeling of the viral capsid with mCherry fluorescent protein. To test this dual modality system, we constructed the Ad5/3Δ24pIXcherry/SSTR CRAd and validated its capacity to generate fluorescent and nuclear signals in vitro and following intratumoral injection. Analysis of 64Cu-CB-TE2A-Y3-TATE biodistribution in mice revealed reduced uptake in tumors injected with the imaging CRAd relative to the replication-incompetent, Ad-expressing SSTR2 but significantly greater uptake compared to the negative CRAd control. Optical imaging demonstrated relative correlation of fluorescent signal with virus replication as determined by viral genome quantification in tumors. Positron emission tomography/computed tomography studies demonstrated that we can visualize radioactive uptake in tumors injected with imaging CRAd and the trend for greater uptake by standardized uptake value analysis compared to control CRAd. In the aggregate, the plasticity of our dual imaging approach should provide the technical basis for monitoring CRAd biodistribution and persistence in preclinical studies while offering potential utility for a range of clinical applications.

  9. Hans Strahl's pioneering studies in comparative placentation

    DEFF Research Database (Denmark)

    Carter, Anthony Michael; Mess, A

    2010-01-01

    Hans Strahl, a contemporary of Duval and Hubrecht, made many important contributions to comparative placentation. Despite this he is not well known and some of his original observations tend to be attributed to later authors. Strahl published a classification of placental types based on their shape...... of the most important findings made by Strahl including work on placentation in carnivores and higher primates that remains unsurpassed....

  10. Comparative study of some new EPR dosimeters

    International Nuclear Information System (INIS)

    Alzimami, K.S.; Maghraby, Ahmed M.; Bradley, D.A.

    2014-01-01

    Investigations have been made of four new radiation dosimetry EPR candidates from the same family of materials: sulfamic acid, sulfanillic acid, homotaurine, and taurine. Mass energy attenuation coefficients, mass stopping power values and the time dependence of the radiation induced radicals are compared. Also investigated are the microwave saturation behavior and the effect of applied modulation amplitude on both peak-to-peak line width (W PP ) and peak-to-peak signal height (H PP ). The dosimeters are characterized by simple spectra and stable radiation-induced radicals over reasonable durations, especially in taurine dosimeters. Sulfamic acid dosimeters possessed the highest sensitivity followed by taurine and homotaurine and sulfanillic. - Highlights: ► Several EPR dosimeters were suggested based on SO 3 − radical. ► Taurine, homotaurine, sulfanilic, and sulfamic acid all possess simple EPR spectra. ► Dosimeters were compared to each other in terms of the dosimetric point of view. ► Energy dependence curves of the selected dosimeters were compared to eachother

  11. Bioavailability and biodistribution of nanodelivered lutein

    Science.gov (United States)

    The aim of the study was to evaluate the ability of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NP) to enhance lutein bioavailability. The bioavailability of free lutein and PLGA-NP lutein in rats was assessed by determining plasma pharmacokinetics and deposition in selected tissues. Lutein ...

  12. Biodistribution of Carbon Nanotubes in Animal Models

    DEFF Research Database (Denmark)

    Jacobsen, Nicklas Raun; Møller, Peter Horn; Clausen, Per Axel

    2017-01-01

    the main sites of long-term CNT accumulation, which also includes pleura, a major site for fibre-induced pulmonary diseases. Studies on intravenous injection show that CNT in blood circulation are cleared relatively fast with a half-life of minutes or hours. The major target organs were the same...

  13. Comparative transport studies of ''1212'' superconductors

    International Nuclear Information System (INIS)

    Gapud, Albert; Wu, Judy; Yan, Shaolin; Xie, Yi-Yuan; Kang, Byeongwon; Siegal, Michael P.; Overmyer, Donald L.

    2000-01-01

    HgBa 2 CaCu 2 O 6+δ (Hg-1212) thin films were fabricated by exchanging the TI cations in TlBa 2 CaCu 2 O 7-δ (Tl-1212) thin films with Hg cations, causing a 30-K increase in Tc. To determine how this exchange effects such a Tc increase, the irreversibility lines, temperature dependence of critical current density, and temperature dependence of Hall angle of Hg-1212 and T1-1212 thin films were measured and then compared. The results strongly suggest that the Tc shift is caused by a doubling of charge carrier density

  14. Th biodistribution in internal contamination of animals

    International Nuclear Information System (INIS)

    Ciubotariu, M.; Danis, A.; Dumitrescu, G.; Cucu, M.

    1999-01-01

    Fissionable elements (U,Th) internal contamination have been studied using the fission track method as analysis method of the U and/or Th contaminant elements and Wistar-London breed rats as experiment animals. Different ways to obtain internal contaminations have been investigated: ingestion, inhalation, absorption by skin and through wounds. After the U internal contamination study was carried out, in this stage the Th internal contamination by ingestion is in progress. Using the identical aliquot parts of a solution calibrated in Th, corresponding to an Annual Limit Intake, three Wistar-London breed rats were contaminated. They were kept in normal life conditions and under permanent medical surveillance up to their sacrification. The animals were sacrificed at different time intervals after their contamination: 2 days, 7 days and 14 days, respectively. After the sacrification, their vital organs were sampled, weighed, calcined, re-weighed and finally analysed by track detection using the fission track micro-mappings technique. Also, their evacuations were sampled every 24 hours weighed, calcined and analysed in the same way as the vital organs. The Th fission track micro-mappings technique was used in the following conditions: - mica-muscovite as track detector pre-etched for fossil tracks 18 h in HF-40 per cent at room temperature; - the neutron irradiations were performed in the nuclear reactor VVR-S Bucharest at the neutron fluences of 3.10 15 - 2.10 16 fast neutrons/c m 2 ; - the visualization of the Th induced fission tracks were obtained by chemical etching in HF-40 per cent, 3 h at room temperature; - the Th track micro-mappings obtained in track detectors were studied by optical microscopy using a stereo microscope WILD M7S for ensemble study (X6-X31) and a binocular ZEISS JENA microscope for qualitative and quantitative studies (X150). The biological reference materials calibrated in Th were prepared in our laboratory using the calcined organs and the

  15. Advertisement Analysis: A Comparative Critical Study

    Science.gov (United States)

    Abdelaal, Noureldin Mohamed; Sase, Amal Saleh

    2014-01-01

    This study aimed at analyzing two advertisements, and investigating how advertisers use discourse and semiotics to make people and customers buy into their ideas, beliefs, or simply their products. The two advertisements analyzed are beauty products which have been selected from internet magazines. The methodology adopted in this study is…

  16. Comparative studies on different molecular methods for ...

    African Journals Online (AJOL)

    The present study aims to evaluate two molecular methods for epidemiological typing of multi drug resistant Klebsiella pneumoniae isolated from Mansoura Hospitals. In this study, a total of 300 clinical isolates were collected from different patients distributed among Mansoura Hospitals, Dakahlia governorate, Egypt.

  17. A Comparative Comment on the Case Studies

    DEFF Research Database (Denmark)

    Kjeldsen, Christian Christrup; Ley, Thomas; Jensen, Niels Rosendal

    2012-01-01

    Denne konklusion sammenfatter hovedtrækkene af de gennemførte case studies i WorkAble-projektet. Vigtige pointer er, at unge på tværs af de forskellige case studies har vanskeligt ved at blive hørt og taget alvorligt. I stedet spises de af med "realistisk vejledning" eller dårlige uddannelses- og...

  18. Comparative study of environmental impact assessment methods ...

    African Journals Online (AJOL)

    This study aims to introduce and systematically investigate the environmental issues during important decision-making stages. Meanwhile, impacts of development on the environmental components will be also analyzed. This research studies various methods of predicting the environmental changes and determining the ...

  19. Safety, Pharmacokinetics, Immunogenicity, and Biodistribution of (186)Re-Labeled Humanized Monoclonal Antibody BIWA 4 (Bivatuzumab( in Patients with Early-Stage Breast Cancer.

    NARCIS (Netherlands)

    Koppe, M.; Schaijk, F. van; Roos, J.C.; Leeuwen, P.; Heider, K.H.; Kuthan, H.; Bleichrodt, R.P.

    2004-01-01

    The aim of this prospective study was to evaluate the safety, pharmacokinetics, immunogenicity, and biodistribution of (186)Re-labeled humanized anti-CD44v6 monoclonal antibody (MAb( BIWA 4 (Bivatuzumab( in 9 patients with early-stage breast cancer. Radioimmunoscintigraphy (RIS( was performed within

  20. Synthesis and biodistribution of some radioiodinated diamines

    International Nuclear Information System (INIS)

    Joshua, A.V; Sandfor, J.G.; Scott, J.R.; Muddukrishna, S.N.

    1987-01-01

    It was felt that investigations of somke side chain analogues of HIPDM [N,N,N'-trimethyl-N'-(2-hydroxy-3-methyl-5-iodo-benzyl)-1,3-propanediamine] may help elucidate some of the factors necessary for the uptake and retention of radiolabelled compounds by the brain. All compounds investigated showed significant initial brain uptake in mice. When the side chain is shortened by one carbon, there is high initial brain activity but this falls very rapidly. These results indicate that the particular side chain seen in HIPDM is important for brain retention. Several of the compounds which are reporting here, have also pancreatic uptake and the study in mece and rats are included. (M.E.L.) [es

  1. Nonlinear analysis of RED - a comparative study

    International Nuclear Information System (INIS)

    Jiang Kai; Wang Xiaofan; Xi Yugeng

    2004-01-01

    Random Early Detection (RED) is an active queue management (AQM) mechanism for routers on the Internet. In this paper, performance of RED and Adaptive RED are compared from the viewpoint of nonlinear dynamics. In particular, we reveal the relationship between the performance of the network and its nonlinear dynamical behavior. We measure the maximal Lyapunov exponent and Hurst parameter of the average queue length of RED and Adaptive RED, as well as the throughput and packet loss rate of the aggregate traffic on the bottleneck link. Our simulation scenarios include FTP flows and Web flows, one-way and two-way traffic. In most situations, Adaptive RED has smaller maximal Lyapunov exponents, lower Hurst parameters, higher throughput and lower packet loss rate than that of RED. This confirms that Adaptive RED has better performance than RED

  2. Comparative study of void fraction models

    International Nuclear Information System (INIS)

    Borges, R.C.; Freitas, R.L.

    1985-01-01

    Some models for the calculation of void fraction in water in sub-cooled boiling and saturated vertical upward flow with forced convection have been selected and compared with experimental results in the pressure range of 1 to 150 bar. In order to know the void fraction axial distribution it is necessary to determine the net generation of vapour and the fluid temperature distribution in the slightly sub-cooled boiling region. It was verified that the net generation of vapour was well represented by the Saha-Zuber model. The selected models for the void fraction calculation present adequate results but with a tendency to super-estimate the experimental results, in particular the homogeneous models. The drift flux model is recommended, followed by the Armand and Smith models. (F.E.) [pt

  3. Nonlinear analysis of RED - a comparative study

    Energy Technology Data Exchange (ETDEWEB)

    Jiang Kai; Wang Xiaofan E-mail: xfwang@sjtu.edu.cn; Xi Yugeng

    2004-09-01

    Random Early Detection (RED) is an active queue management (AQM) mechanism for routers on the Internet. In this paper, performance of RED and Adaptive RED are compared from the viewpoint of nonlinear dynamics. In particular, we reveal the relationship between the performance of the network and its nonlinear dynamical behavior. We measure the maximal Lyapunov exponent and Hurst parameter of the average queue length of RED and Adaptive RED, as well as the throughput and packet loss rate of the aggregate traffic on the bottleneck link. Our simulation scenarios include FTP flows and Web flows, one-way and two-way traffic. In most situations, Adaptive RED has smaller maximal Lyapunov exponents, lower Hurst parameters, higher throughput and lower packet loss rate than that of RED. This confirms that Adaptive RED has better performance than RED.

  4. Biodistribution and dosimetry of {sup 123}I-mZIENT: a novel ligand for imaging serotonin transporters

    Energy Technology Data Exchange (ETDEWEB)

    Nicol, Alice [NHS Greater Glasgow and Clyde, Department of Nuclear Medicine, Southern General Hospital, Glasgow (United Kingdom); Krishnadas, Rajeev [University of Glasgow, Sackler Institute of Psychobiological Research, Glasgow (United Kingdom); Champion, Sue [University of Glasgow, Institute of Neuroscience and Psychology, College of Medical, Veterinary and Life Sciences, Glasgow (United Kingdom); Tamagnan, Gilles [Institute for Neurodegenerative Disorders, New Haven, CT (United States); Stehouwer, Jeffrey S.; Goodman, Mark M. [Emory University, Department of Radiology and Imaging Sciences, Atlanta, GA (United States); Hadley, Donald M. [NHS Greater Glasgow and Clyde, Department of Neuro-Radiology, Institute of Neurological Sciences, Glasgow (United Kingdom); Pimlott, Sally L. [NHS Greater Glasgow and Clyde, West of Scotland Radionuclide Dispensary, Glasgow (United Kingdom)

    2012-05-15

    {sup 123}I-labelled mZIENT (2{beta}-carbomethoxy-3{beta}-(3'-((Z)-2-iodoethenyl)phenyl)nortropane) has been developed as a radioligand for the serotonin transporter. The aim of this preliminary study was to assess its whole-body biodistribution in humans and estimate dosimetry. Three healthy controls and three patients receiving selective serotonin reuptake inhibitor (SSRI) therapy for depression were included (two men, four women, age range 41-56 years). Whole-body imaging, brain SPECT imaging and blood and urine sampling were performed. Whole-body images were analysed using regions of interest (ROIs), time-activity curves were derived using compartmental analysis and dosimetry estimated using OLINDA software. Brain ROI analysis was performed to obtain specific-to-nonspecific binding ratios in the midbrain, thalamus and striatum. Initial high uptake in the lungs decreased in later images. Lower uptake was seen in the brain, liver and intestines. Excretion was primarily through the urinary system. The effective dose was estimated to be of the order of 0.03 mSv/MBq. The organ receiving the highest absorbed dose was the lower large intestine wall. Uptake in the brain was consistent with the known SERT distribution with higher specific-to-nonspecific binding in the midbrain, thalamus and striatum in healthy controls compared with patients receiving SSRI therapy. {sup 123}I-mZIENT may be a promising radioligand for imaging the serotonin transporters in humans with acceptable dosimetry. (orig.)

  5. Influence of splenectomy on the biodistribution of technetium-99m dimercaptosuccinic acid (99mTc-DMSA) in rats

    International Nuclear Information System (INIS)

    Acucena, Maria Kadja Meneses Torres; Pereira, Kercia Regina Santos Gomes; Villarim Neto, Arthur; Rego, Amalia Cinthia Meneses; Bernardo-Filho, Mario; Azevedo, Italo Medeiros; Araujo Filho, Irami; Medeiros, Aldo Cunha

    2008-01-01

    This study aimed to evaluate if the splenectomy alters the biodistribution of 99mTc-DMSA and renal function in Wistar rats. The animals were separated in the groups: splenectomy (n = 6) and control (n = 6). After splenectomy (15 days), the administration of 0.1 ml of 99mTc-DMSA IV (0.48 MBq) was carried out. Thirty minutes later, kidney, heart, lung, thyroid, stomach, bladder and femur and samples of blood were isolated. The organs were weighed, counted and the percentage of radioactivity /g (%ATI/g) determined. Serum urea and creatinine, hematocrit, leukocytes and platelets were measured. Statistics by t test (p<0.05) was done. There was a significant reduction in %ATI/g in kidney and blood (p<0.05) of splenectomized animals, a significant increase (p<0.05) of urea (88.8 ± 18.6 mg/dL) and creatinine (0.56 ± 0.08 mg/dL), compared to the controls (51.5±1.6, 0.37±0.02 mg/dL, respectively), as well as increase in platelets and leucocytes, and hematocrit reduction. The analysis of the results indicates that in rats, splenectomy seems to alter the renal function and the uptake of 99mTc-DMSA. (author)

  6. Influence of splenectomy on the biodistribution of technetium-99m dimercaptosuccinic acid (99mTc-DMSA) in rats

    Energy Technology Data Exchange (ETDEWEB)

    Acucena, Maria Kadja Meneses Torres; Pereira, Kercia Regina Santos Gomes; Villarim Neto, Arthur; Rego, Amalia Cinthia Meneses [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Centro de Ciencias da Saude; Bernardo-Filho, Mario [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes. Dept. de Biofisica e Biometria; Azevedo, Italo Medeiros; Araujo Filho, Irami; Medeiros, Aldo Cunha [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Dept. de Cirurgia]. E-mail: aldo@ufrnet.br

    2008-12-15

    This study aimed to evaluate if the splenectomy alters the biodistribution of 99mTc-DMSA and renal function in Wistar rats. The animals were separated in the groups: splenectomy (n = 6) and control (n = 6). After splenectomy (15 days), the administration of 0.1 ml of 99mTc-DMSA IV (0.48 MBq) was carried out. Thirty minutes later, kidney, heart, lung, thyroid, stomach, bladder and femur and samples of blood were isolated. The organs were weighed, counted and the percentage of radioactivity /g (%ATI/g) determined. Serum urea and creatinine, hematocrit, leukocytes and platelets were measured. Statistics by t test (p<0.05) was done. There was a significant reduction in %ATI/g in kidney and blood (p<0.05) of splenectomized animals, a significant increase (p<0.05) of urea (88.8 {+-} 18.6 mg/dL) and creatinine (0.56 {+-} 0.08 mg/dL), compared to the controls (51.5{+-}1.6, 0.37{+-}0.02 mg/dL, respectively), as well as increase in platelets and leucocytes, and hematocrit reduction. The analysis of the results indicates that in rats, splenectomy seems to alter the renal function and the uptake of 99mTc-DMSA. (author)

  7. Samarium oxide as a radiotracer to evaluate the in vivo biodistribution of PLGA nanoparticles

    CSIR Research Space (South Africa)

    Mandiwana, V

    2015-09-01

    Full Text Available the biodistribution of poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles containing samarium-153 oxide ([(sup153)Sm]Sm(sub2)O(sub3)) in vivo to prove that orally administered nanoparticles alter the biodistribution of a drug. These were then activated in a nuclear...

  8. War And Reconstruction: Four Comparative Case Studies

    African Journals Online (AJOL)

    The four case studies are taken from four different continents, four different wars under .... and revolutionary changes in the structures and power relations in society and ..... general public accept nowadays that although states' rights were the ...

  9. Phytochemical screening and study of comparative antibacterial ...

    African Journals Online (AJOL)

    SARAH

    2013-06-30

    Jun 30, 2013 ... Objectives: In this study, methanol, ethanol and aqueous extracts of ... of resistance in bacteria previously susceptible to ... increase in antibiotic resistance in hospitals and ..... extraction process (Masoko et al., 2008). Use of ...

  10. COMPARATIVE STUDY OF HONEY COLLECTED FROM ...

    African Journals Online (AJOL)

    lanez

    2014-06-30

    Jun 30, 2014 ... content, electrical conductivity, total dissolved solids, color intensity ... used in this study on the basis of date of harvest, geographical origin. ... The determination of physical and chemical parameters such as content of water, ...

  11. Comparative study of connectivity in telemedicine.

    Science.gov (United States)

    Singh, Indra Pratap; Kapoor, Lily; Daman, Repu; Mishra, Saroj Kanta

    2008-10-01

    Communication links are the lifelines for telemedicine practice. Various terrestrial and satellite media can be used; however, each has its own plus and minus side. The current study was designed to evaluate three types of telecommunication media used for telemedical videoconference at the Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow Telemedicine program over a period of 20 months. The evaluation was based on analysis of technical parameters recorded in a prescribed proforma designed for the study purpose and maintained prospectively after completion of each event. Only technical issues were addressed. At the end of the study period, analysis of data revealed that leased line-based terrestrial Internet Protocol (IP) was better than Sky IP. Integrated Services Digital Network media were found technically less acceptable for telemedical videoconference.

  12. Child Labor in Africa: A Comparative Study

    DEFF Research Database (Denmark)

    Canagarajah, Sudharshan; Nielsen, Helena Skyt

    2001-01-01

    This paper analyzes the determinants of child labor in Africa as inferred from recent empirical studies. The empirical analysis is based upon five country studies undertaken in three different African countries, namely Côte d'Ivoire, Ghana, and Zambia. Some support is found for the popular belief...... of poverty as a determinant of child labor, however other determinants are of similar importance. Among school costs, transportation costs have the greatest effect on child labor and school attendance, whereas the hypothesis of imperfect capital markets and that of household composition generally find some...

  13. Child Labor in Africa: A Comparative Study

    DEFF Research Database (Denmark)

    Nielsen, Helena Skyt; Canagarajah, Sudharshan

    1999-01-01

    This paper analyzes the determinants of child labor in Africa as inferred from recent empirical studies. The empirical analysis is based upon five country studies undertaken in three different African countries, namely Côte d'Ivoire, Ghana, and Zambia. Some support is found for the popular belief...... of poverty as a determinant of child labor, however other determinants are of similar importance. Among school costs, transportation costs have the greatest effect on child labor and school attendance, whereas the hypothesis of imperfect capital markets and that of household composition generally find some...

  14. Comparative Anticonvulsant Study of Epoxycarvone Stereoisomers

    Directory of Open Access Journals (Sweden)

    Paula Regina Rodrigues Salgado

    2015-10-01

    Full Text Available Stereoisomers of the monoterpene epoxycarvone (EC, namely (+-cis-EC, (−-cis-EC, (+-trans-EC, and (−-trans-EC, were comparatively evaluated for anticonvulsant activity in specific methodologies. In the pentylenetetrazole (PTZ-induced anticonvulsant test, all of the stereoisomers (at 300 mg/kg increased the latency to seizure onset, and afforded 100% protection against the death of the animals. In the maximal electroshock-induced seizures (MES test, prevention of tonic seizures was also verified for all of the isomers tested. However, the isomeric forms (+ and (−-trans-EC showed 25% and 12.5% inhibition of convulsions, respectively. In the pilocarpine-induced seizures test, all stereoisomers demonstrated an anticonvulsant profile, yet the stereoisomers (+ and (−-trans-EC (at 300 mg/kg showed a more pronounced effect. A strychnine-induced anticonvulsant test was performed, and none of the stereoisomers significantly increased the latency to onset of convulsions; the stereoisomers probably do not act in this pathway. However, the stereoisomers (+-cis-EC and (+-trans-EC greatly increased the latency to death of the animals, thus presenting some protection. The four EC stereoisomers show promise for anticonvulsant activity, an effect emphasized in the isomers (+-cis-EC, (+-trans-EC, and (−-trans-EC for certain parameters of the tested methodologies. These results serve as support for further research and development of antiepileptic drugs from monoterpenes.

  15. Comparative study on software development methodologies

    Directory of Open Access Journals (Sweden)

    Mihai Liviu DESPA

    2014-12-01

    Full Text Available This paper focuses on the current state of knowledge in the field of software development methodologies. It aims to set the stage for the formalization of a software development methodology dedicated to innovation orientated IT projects. The paper starts by depicting specific characteristics in software development project management. Managing software development projects involves techniques and skills that are proprietary to the IT industry. Also the software development project manager handles challenges and risks that are predominantly encountered in business and research areas that involve state of the art technology. Conventional software development stages are defined and briefly described. Development stages are the building blocks of any software development methodology so it is important to properly research this aspect. Current software development methodologies are presented. Development stages are defined for every showcased methodology. For each methodology a graphic representation is illustrated in order to better individualize its structure. Software development methodologies are compared by highlighting strengths and weaknesses from the stakeholder's point of view. Conclusions are formulated and a research direction aimed at formalizing a software development methodology dedicated to innovation orientated IT projects is enunciated.

  16. Toucan and hornbill beaks: a comparative study.

    Science.gov (United States)

    Seki, Yasuaki; Bodde, Sara G; Meyers, Marc A

    2010-02-01

    The structure and mechanical behavior of Toco Toucan (Ramphastos toco) and Wreathed Hornbill (Rhyticeros undulatus) beaks were compared. The beak of both species is a sandwich-structured composite, having an exterior, or rhamphotheca, consisting of multiple layers of keratin scales and a core composed of a fibrous network of bony closed-cell foam. The rhamphotheca is an arrangement of approximately 50microm diameter, overlapping, keratin tiles. The hornbill rhamphotheca exhibits a surface morphology on the ridged casque that is distinguishable from that observed on the bill proper. Intermediate filaments in the keratin matrix were observed by transmission electron microscopy. The Young's modulus measurements of toucan rhamphotheca indicate isotropy in longitudinal and transverse directions, whereas those of hornbill rhamphotheca may suggest anisotropy. The compressive response of beak foam is governed by brittle crushing behavior. The crushing strength of hornbill foam is six times higher than that of toucan foam. Micro- and nanoindentation hardness values were measured for rhamphotheca and foam trabeculae of toucan and hornbill specimens. The sandwich design of beaks was analyzed using the Karam-Gibson and Dawson-Gibson models. The presence of a cellular core increases the bending resistance (Brazier moment) by a factor of 3-6 while decreasing the compressive strength by only 50%.

  17. Comparative study of two treatment planning systems

    International Nuclear Information System (INIS)

    Ramos Caballero, L. J.; Quinones Rodriguez, L. A.; Lupiani Castellanos, J.

    2013-01-01

    In this study of the comparison of the clinical dosimetry between planners can deduce that the differences are in the majority of the cases below 3%, and only in cases where the field size is small, we found significant discrepancies, although justifiable. On the one hand it is different calculation algorithm and implementation on the other, the modeling of the accelerator. (Author)

  18. COMPARATIVE STUDY OF CONSERVATIVE RESECTION AND ...

    African Journals Online (AJOL)

    1999-05-05

    May 5, 1999 ... Depmment of Surgery, University Teaching Hospital, PMB 2076. Jos, Nigeria ... Design: A retrospective study of patients with thyroid cancers that were managed during an ... This logical basis for either cure or palliation of a .... palliative purposes. A mixed ... Pulmonary metastasis are usually of the classical.

  19. Metacognition and Group Differences: A Comparative Study

    Science.gov (United States)

    Al-Hilawani, Yasser A.

    2014-01-01

    In this study, metacognition refers to performing visual analysis and discrimination of real life events and situations in naïve psychology, naïve physics, and naïve biology domains. It is used, along with measuring reaction time, to examine differences in the ability of four groups of students to select appropriate pictures that correspond with…

  20. Children's Friendship Development: A Comparative Study

    Science.gov (United States)

    Yu, SeonYeong; Ostrosky, Michaelene M.; Fowler, Susan A.

    2011-01-01

    Establishing friendships is an important developmental goal of early childhood, but little research has addressed ways in which parents support the friendship development of their young children with disabilities. The purpose of this survey study was to explore the support strategies that parents use to facilitate their children's friendships.…

  1. Comparative study of fixation density maps

    NARCIS (Netherlands)

    Engelke, U.; Liu, H.; Wang, Junle; Callet, Le P.; Heynderickx, I.E.J.; Zepernick, H.-J.; Maeder, A.

    2013-01-01

    Fixation density maps (FDM) created from eye tracking experiments are widely used in image processing applications. The FDM are assumed to be reliable ground truths of human visual attention and as such, one expects a high similarity between FDM created in different laboratories. So far, no studies

  2. Comparison of the biodistribution of manganese-54 DTPA and gadolinium-153 DTPA in dogs

    International Nuclear Information System (INIS)

    Boudreau, R.J.; Burbidge, S.; Sirr, S.; Loken, M.K.

    1987-01-01

    The biodistribution of [ 54 Mn]DTPA and [ 153 Gd]DTPA dimeglumine were investigated and compared following i.v. administration to fasting anesthetized dogs. Unlike most previously reported metal ion-DTPA complexes, [ 54 Mn]DTPA showed high uptakes in several organs including the liver, bile, pancreas, bowel, and kidney. This uptake was independent of the pH of the injected solution. Accumulation in these organs suggests a potential role for [Mn]DTPA as a paramagnetic contrast agent for NMR imaging. With the exception of the kidneys, [ 153 Gd]DTPA showed no evidence of tissue specific uptake over the course of 4 hr, consistent with it being an extracellular ion that is cleared by glomerular filtration

  3. A standardised study to compare prostate cancer targeting efficacy of five radiolabelled bombesin analogues

    Energy Technology Data Exchange (ETDEWEB)

    Schroeder, Rogier P.J. [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Erasmus MC, Department of Experimental Urology, Rotterdam (Netherlands); Mueller, Cristina; Melis, Marleen L.; Breeman, Wout A.P.; Blois, Erik de; Krenning, Eric P.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Reneman, Suzanne; Bangma, Chris H.; Weerden, Wytske M. van [Erasmus MC, Department of Experimental Urology, Rotterdam (Netherlands)

    2010-07-15

    Prostate-specific antigen (PSA)-based screening for prostate cancer (PC) has dramatically increased early diagnosis. Current imaging techniques are not optimal to stage early PC adequately. A promising alternative to PC imaging is peptide-based scintigraphy using radiolabelled bombesin (BN) analogues that bind to gastrin-releasing peptide receptors (GRPR) being overexpressed in PC. When labelled to appropriate radionuclides BN targeting of GRPRs may also provide applications for peptide radionuclide receptor therapy (PRRT). Assessment studies under identical experimental conditions allowing a reliable comparison of the potential of such analogues are lacking. This study was performed to evaluate and directly compare five promising radiolabelled BN analogues for their targeting efficacy for PC under standardised conditions. The BN agonists [{sup 111}In]DOTA-PESIN, [{sup 111}In]AMBA, [{sup 111}In]MP2346 and [{sup 111}In]MP2653 and one antagonist [{sup 99m}Tc]Demobesin-1 were evaluated in GRPR-overexpressing human PC-3 tumour-bearing mice to determine peptide stability in vivo, biodistribution and GRPR targeting potential by animal SPECT/CT imaging and ex vivo autoradiography. HPLC analysis of blood showed intact Demobesin-1 at 5 and 15 min after injection (64.1{+-}1.6% and 41.0{+-}01%, respectively) being much less for the other compounds. AMBA, the second most stable analogue, showed 36.1{+-}2.7% and 9.8{+-}1.1% intact peptide after 5 and 15 min. PC-3 tumour uptake at 1 h was comparable for Demobesin-1, AMBA, PESIN and MP2346 (3.0{+-}0.4, 2.7{+-}0.5, 2.3{+-}0.5 and 2.1{+-}0.9%ID/g, respectively), but very low for MP2653 (0.9 {+-} 0.2%ID/g). In addition, MP2346 showed undesirably high uptake in the kidneys (7.9{+-}1.9%ID/g) being significantly less for the other analogues. AMBA, MP2346 and PESIN revealed favourable increases in tumour to blood ratios over time while changes in tumour to kidney and pancreas ratios for Demobesin-1 from 1 to 24 h after injection were

  4. Earthquake correlations and networks: A comparative study

    Science.gov (United States)

    Krishna Mohan, T. R.; Revathi, P. G.

    2011-04-01

    We quantify the correlation between earthquakes and use the same to extract causally connected earthquake pairs. Our correlation metric is a variation on the one introduced by Baiesi and Paczuski [M. Baiesi and M. Paczuski, Phys. Rev. E EULEEJ1539-375510.1103/PhysRevE.69.06610669, 066106 (2004)]. A network of earthquakes is then constructed from the time-ordered catalog and with links between the more correlated ones. A list of recurrences to each of the earthquakes is identified employing correlation thresholds to demarcate the most meaningful ones in each cluster. Data pertaining to three different seismic regions (viz., California, Japan, and the Himalayas) are comparatively analyzed using such a network model. The distribution of recurrence lengths and recurrence times are two of the key features analyzed to draw conclusions about the universal aspects of such a network model. We find that the unimodal feature of recurrence length distribution, which helps to associate typical rupture lengths with different magnitude earthquakes, is robust across the different seismic regions. The out-degree of the networks shows a hub structure rooted on the large magnitude earthquakes. In-degree distribution is seen to be dependent on the density of events in the neighborhood. Power laws, with two regimes having different exponents, are obtained with recurrence time distribution. The first regime confirms the Omori law for aftershocks while the second regime, with a faster falloff for the larger recurrence times, establishes that pure spatial recurrences also follow a power-law distribution. The crossover to the second power-law regime can be taken to be signaling the end of the aftershock regime in an objective fashion.

  5. Earthquake correlations and networks: A comparative study

    International Nuclear Information System (INIS)

    Krishna Mohan, T. R.; Revathi, P. G.

    2011-01-01

    We quantify the correlation between earthquakes and use the same to extract causally connected earthquake pairs. Our correlation metric is a variation on the one introduced by Baiesi and Paczuski [M. Baiesi and M. Paczuski, Phys. Rev. E 69, 066106 (2004)]. A network of earthquakes is then constructed from the time-ordered catalog and with links between the more correlated ones. A list of recurrences to each of the earthquakes is identified employing correlation thresholds to demarcate the most meaningful ones in each cluster. Data pertaining to three different seismic regions (viz., California, Japan, and the Himalayas) are comparatively analyzed using such a network model. The distribution of recurrence lengths and recurrence times are two of the key features analyzed to draw conclusions about the universal aspects of such a network model. We find that the unimodal feature of recurrence length distribution, which helps to associate typical rupture lengths with different magnitude earthquakes, is robust across the different seismic regions. The out-degree of the networks shows a hub structure rooted on the large magnitude earthquakes. In-degree distribution is seen to be dependent on the density of events in the neighborhood. Power laws, with two regimes having different exponents, are obtained with recurrence time distribution. The first regime confirms the Omori law for aftershocks while the second regime, with a faster falloff for the larger recurrence times, establishes that pure spatial recurrences also follow a power-law distribution. The crossover to the second power-law regime can be taken to be signaling the end of the aftershock regime in an objective fashion.

  6. Evaluation of tumoral enhancement by superparamagnetic iron oxide particles: comparative studies with ferumoxtran and anionic iron oxide nanoparticles

    International Nuclear Information System (INIS)

    Brillet, P-Y.; Gazeau, F.; Luciani, A.; Bessoud, B.; Cuenod, C.-A.; Siauve, N.; Pons, J.-N.; Poupon, J.; Clement, O.

    2005-01-01

    This study was designed to compare tumor enhancement by superparamagnetic iron oxide particles, using anionic iron oxide nanoparticles (AP) and ferumoxtran. In vitro, relaxometry and media with increasing complexity were used to assess the changes in r2 relaxivity due to cellular internalization. In vivo, 26 mice with subcutaneously implanted tumors were imaged for 24 h after injection of particles to describe kinetics of enhancement using T1 spin echo, T2 spin echo, and T2 fast spin echo sequences. In vitro, the r2 relaxivity decreased over time (0-4 h) when AP were uptaken by cells. The loss of r2 relaxivity was less pronounced with long (Hahn Echo) than short (Carr-Purcell-Meiboom-Gill) echo time sequences. In vivo, our results with ferumoxtran showed an early T2 peak (1 h), suggesting intravascular particles and a second peak in T1 (12 h), suggesting intrainterstitial accumulation of particles. With AP, the late peak (24 h) suggested an intracellular accumulation of particles. In vitro, anionic iron oxide nanoparticles are suitable for cellular labeling due to a high cellular uptake. Conversely, in vivo, ferumoxtran is suitable for passive targeting of tumors due to a favorable biodistribution. (orig.)

  7. Conjunctivitis in the newborn- A comparative study

    Directory of Open Access Journals (Sweden)

    Meenakshi Wadhwani

    2011-01-01

    Full Text Available Background: Conjunctivitis of the newborn is defined as hyperemia and eye discharge in the neonates and is a common infection occurring in the neonates in the first month of life. In the United States, the incidence of neonatal conjunctivitis ranges from 1-2%, in India, the prevalence is 0.5-33% and varies in the world from 0.9-21% depending on the socioeconomic status. Aim: To study the organisms causing conjunctivitis of the newborn and to correlate the etiology with the mode of delivery. Design: Single center, prospective, observational study. Materials and Methods: A total of 300 mothers and their newborns, born over a period of one year, were included in the study. Of these 200 newborns were delivered through vaginal route (Group A and 100 (Group B delivered by lower segment caesarean section (LSCS. At the time of labour, high vaginal swabs were taken from the mothers. Two conjunctival swabs each from both eyes of the newborn were collected at birth and transported to Microbiology department in a candle jar immediately. Results: Eight babies in Group A, developed conjunctivitis at birth. None of the babies in Group B developed conjunctivitis, this difference was statistically highly significant (P<0.000. The organisms found in the conjunctiva of the newborns in Group A were Coagulase negative Staphylococcus, α hemolytic Streptococcus, Escherichia coli and Pseudomonas spps. However, the commonest organism leading to conjunctivitis in the newborn in this study was Coagulase negative Staphylococcus. It was observed that the mothers of 5 out of 8 babies (60% developing conjunctivitis gave history of midwife interference and premature rupture of membranes so the presence of risk factors contribute to the occurrence of conjunctivitis in the newborn. Conclusions: It is inferred that the mode of delivery and the presence of risk factors is responsible for conjunctivitis in the newborn.

  8. Comparative study of radon in Sudan

    International Nuclear Information System (INIS)

    Gharbi, Shaza Ismail Mohammed

    2014-07-01

    This study was conducted primarily to contribute radon data for radon map in Sudan and identify regions with elevated radon levels and improve data collection and analysis for the future radon levels evaluation. This study partially covered three states of Sudan ( Red Sea - Khartoum - South Khordofan). Previous work done has been considered in this study which focused and investigated the levels of radon concentration in ( indoor radon gas and water) by using gamma spectrometry equipped with ( HPGe detector) or (Na1 (T1) detector). The results obtained are within the acceptable levels and dose not poses any risk from radiation protection point of view. Red Sea state ( port-sudan): (124.39±6.21) Bq/m 3 . Khartoum state ( Suba): (151.52) Bq/m 3 . (Omdurman): ( 127±23) Bq/m 3 . Radon in water: (59) Bq/L. South Kordofan State: (102.8) Bq/m 3 . In water (Kadugli): (3 1 39)) Bq/L.(Author)

  9. A comparative study of various decalcification techniques

    Directory of Open Access Journals (Sweden)

    Prathibha Prasad

    2013-01-01

    Full Text Available Background : Study of fibrilar, cellular and sub cellular structures of mineralized tissues is only possible after the removal of the calcium apatite of these tissues by the process of demineralization. Aims: The present study aims to evaluate six commonly used demineralizing agents to identify the best decalcifying agent. Materials and Methods: The present study included six different decalcifying solutions: 10% formal nitric acid, 8% formal nitric acid, 10% formic acid, 8% formic acid, Perenyi′s fluid and Ethylene Di-Amine Tetra Acetic Acid. eight samples of posterior mandible of rat were decalcified in each of the decalcifying solutions and subjected to chemical end-point test. Ehrlich′s Hematoxylin stain was used. Statistical Analysis Used: One way ANOVA was used for multiple group comparisons and Chi-square test was used for analyzing categorical data. P value of 0.05/less was set for statistical significance. Results: Samples treated with EDTA showed the best overall histological impression and the tissue integrity were well preserved. Formal nitric of both the percentages 10 and 8% gave fairly good cellular detail and were rapid in their action. Conclusion: The final impression led to the proposition that EDTA was indeed the best decalcifying agent available. However, with time constraint, the use of formal nitric acid is advocated.

  10. Agoraphobia and Panic Disorder: A Comparative Study

    Directory of Open Access Journals (Sweden)

    Ayse Kart

    2016-01-01

    Full Text Available Aim: In this study we aim to get more information about agoraphobia (AG which is an independent diagnosis in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5 and to evaluate overlaps or differences between agoraphobia and panic disorder (PD upon sociodemographic features and comorbidity with considering relation of these two disorders. Material and Method: Sociodemographic Data Form was given and Structural Clinical Interview for DSM Axis I Disorders (SCID-I was applied to 33 patients diagnosed as AG and 34 patients diagnosed as PD with AG (PDA.Results: AG group consisted of 21 females (63.1%, 12 males (36%, totally 33 patients and PDA group consisted of 23 females (67.6%, 11 males (32.4%, totally 34 patients. Mean age of onset was 32.4±10.2 in PDA group and 31.1±12.1 in AG group. According to sociodemographic features, violence in family and smoking rates were significantly higher in PDA group than AG group. Major Depressive Disorder (MDD as a comorbidity was higher in PDA group. Discussion: In this study, we tried to identify the overlaps and differences of PDA and AG. For a better recognition of AG, further studies are needed.

  11. Iatrogenic alterations in the biodistribution of radiotracers as a result of drug therapy: Reported instances

    International Nuclear Information System (INIS)

    Hladik, W.B. III; Ponto, J.A.; Lentle, B.C.; Laven, D.L.

    1987-01-01

    This chapter is a compilation of reported instances in which the biodistribution of a radiopharmaceutical has been (or could be) modified by the administration of a therapeutic nonradioactive drug or contrast agent in such a way as to potentially interfere with the interpretation of the nuclear medicine study in question. This type of phenomenon is commonly referred to as a drug-radiopharmaceutical interaction. In this chapter, interactions are arranged according to the radiopharmaceutical involved; each interaction is characterized by use of the following descriptors: 1. Interfering drug: the interfering nonradioactive drug that alters the kinetics of the radiopharmaceutical and thus changes the resulting diagnostic data obtained from the study. 2. Nuclear medicine study affected: the nuclear medicine study in which the interaction is likely to occur. 3. Effect on image: the appearance of the image (or the effect on diagnostic data) which results from the interaction. 4. Significance: the potential clinical significance of the interaction

  12. Labeling of scorpion venom with 99mTc and its biodistribution

    International Nuclear Information System (INIS)

    Amin, A.M.

    2013-01-01

    Labeling of scorpion venom (SV) was successfully achieved with 99m Tc using direct chelating method. Venom was labeled with 99m Tc using stannous chloride as reducing agent. Preliminary studies were done to establish the optimum conditions for obtaining the highest yield of the labeled venom. The labeling technique is effective, as a maximum labeling yield (97 %) was obtained after 30-min reaction time by using 80 μg SV in phosphate buffer of pH 7 and 25 μg Sncl 2 ·2H 2 O at room temperature. Venom was injected into normal mice to determine the excretion pathway. Biodistribution studies in normal mice with SV shows rapid clearance of the venom from blood and tissue except for kidneys. The improvement of the immunotherapeutic treatment of envenomation requires a better knowledge of the biological actions of the SV since tissue distribution studies are very important for clinical purpose. (author)

  13. In vivo biodistribution and biological impact of injected carbon nanotubes using magnetic resonance techniques

    Directory of Open Access Journals (Sweden)

    Achraf Al Faraj

    2011-02-01

    Full Text Available Achraf Al Faraj1,2, Florence Fauvelle3, Nathalie Luciani4, Ghislaine Lacroix5, Michael Levy4, Yannick Crémillieux1, Emmanuelle Canet-Soulas1Université Lyon1, Créatis-LRMN, Lyon, France; 2King Saud University, College of Applied Medical Sciences, Radiological Sciences Department, Riyadh, Kingdom of Saudi Arabia; 3CRSSA, Biophysique Cellulaire et Moléculaire, Laboratoire de RMN, La Tronche, France; 4Université Paris7-Paris Diderot, Matières et Systèmes Complexes, Paris, France; 5Institut National de l’Environnement et des Risques Industriels, Verneuil-en-Halatte, FranceBackground: Single-walled carbon nanotubes (SWCNT hold promise for applications as contrast agents and target delivery carriers in the field of nanomedicine. When administered in vivo, their biodistribution and pharmacological profile needs to be fully characterized. The tissue distribution of carbon nanotubes and their potential impact on metabolism depend on their shape, coating, and metallic impurities. Because standard radiolabeled or fluorescently-labeled pharmaceuticals are not well suited for long-term in vivo follow-up of carbon nanotubes, alternative methods are required.Methods: In this study, noninvasive in vivo magnetic resonance imaging (MRI investigations combined with high-resolution magic angle spinning (HR-MAS, Raman spectroscopy, iron assays, and histological analysis ex vivo were proposed and applied to assess the biodistribution and biological impact of intravenously injected pristine (raw and purified and functionalized SWCNT in a 2-week longitudinal study. Iron impurities allowed raw detection of SWCNT in vivo by susceptibility-weighted MRI.Results: A transitional accumulation in the spleen and liver was observed by MRI. Raman spectroscopy, iron assays, and histological findings confirmed the MRI readouts. Moreover, no acute toxicological effect on the liver metabolic profile was observed using the HR-MAS technique, as confirmed by quantitative real

  14. A Comparative Study in Communication Texts & Theories

    Directory of Open Access Journals (Sweden)

    Mahdi Mohsenian Rad

    2011-04-01

    Full Text Available The present article is to study the characteristics and general nature of audience and is described it as "Audience phantasm" in developing countries. It firstly notes that there will be consequences such as audience distancing themselves from local and official media if policy makers and media officials' imaginations of audiences become far from related bare facts have happened in the era of global media and the nature of audiences. Knowing and analyzing the image of audiences presented in new communication theories. Accordingly, as the abovementioned authorities’ viewpoint of audiences exposed to media messages keeps distance from the true nature of media activities, media‐message receivers and their current position in the booming market of media, as termed by Mohsenyan Rad as “Message Bazaar”, there will possibly be disastrous social, cultural, political, and even economic consequences with regard to media uses.Then the history and definitions of “audience”, "uses & gratifications theory" and the concept of "Audience Phantasm" is described. After that, based on those and the increased options as well as the right of selecting of today-audience in the situation of message bazaar, as a result the characteristics of them are explained.

  15. In vivo comparative study of hydroxyapatite labeled with different radioisotopes: evaluation of the scintigraphic images

    Energy Technology Data Exchange (ETDEWEB)

    Couto, Renata Martinussi; Barboza, Marycel Figols de; Souza, Adriano Aparecido de; Muramoto, Emiko; Mengatti, Jair; Araujo, Elaine Bortoleti de, E-mail: rmcouto@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Radiofarmacia

    2008-07-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disorder of joints that is characterized by the inflammation and proliferation of synovial tissues. Approximately 3% of the adult population in the world is affected by this disease which causes pain, joint immobility and disability. Adyo synovectomy (RSV) is a radiotherapeutic modality where a b--emitting radionuclide is administered locally by intra-articular injection on the form of a colloid or radiolabeled particulate. RSV is a well-accepted therapeutic procedure in inflammatory joint diseases and has been successfully employed for more than 50 years as a viable alternative to surgical and chemical synovectomy in the treatment of RA and other inflammatory arthropathies. There are several radionuclides available for this purpose such as {sup 177}Lu, {sup 90}Y, {sup 153}Sm, {sup 165}Dy, and {sup 166}Ho. Hydroxyapatite (HA) is one of the preferred particulates for this application because it is the major chemical constituent of skeletal bone and it is converted into Ca and PO4 ions in the body. In addition HA is completely eliminated over a period of six weeks. The aim of this work is to compare the in vivo stability of hydroxyapatite labeled with {sup 177}Lu, {sup 90}Y and {sup 153}Sm in order to determine the influence of the radionuclide on biological pattern. In biological studies, 100mL of labeled HAs suspended in normal saline were injected into normal knee joints of Wistar rats and the retention of the activity into the synovium was determined. Labeled particles were also injected by intravenous and intramuscular administration, to verify the biodistribution in the case of an eventual leakage of the products from the joint. Sequential scintigraphic images were acquired from 1 hour to 7 days p.i. after anesthetizing the animals with ketamine. Hydroxyapatite was radiolabeled by all radionuclides with high yield. {sup 177}Lu-HA, {sup 90}Y-HA and {sup 153}Sm-HA were retained in the joint for 7 days, showing

  16. In vivo comparative study of hydroxyapatite labeled with different radioisotopes: evaluation of the scintigraphic images

    International Nuclear Information System (INIS)

    Couto, Renata Martinussi; Barboza, Marycel Figols de; Souza, Adriano Aparecido de; Muramoto, Emiko; Mengatti, Jair; Araujo, Elaine Bortoleti de

    2008-01-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disorder of joints that is characterized by the inflammation and proliferation of synovial tissues. Approximately 3% of the adult population in the world is affected by this disease which causes pain, joint immobility and disability. Adyo synovectomy (RSV) is a radiotherapeutic modality where a b--emitting radionuclide is administered locally by intra-articular injection on the form of a colloid or radiolabeled particulate. RSV is a well-accepted therapeutic procedure in inflammatory joint diseases and has been successfully employed for more than 50 years as a viable alternative to surgical and chemical synovectomy in the treatment of RA and other inflammatory arthropathies. There are several radionuclides available for this purpose such as 177 Lu, 90 Y, 153 Sm, 165 Dy, and 166 Ho. Hydroxyapatite (HA) is one of the preferred particulates for this application because it is the major chemical constituent of skeletal bone and it is converted into Ca and PO4 ions in the body. In addition HA is completely eliminated over a period of six weeks. The aim of this work is to compare the in vivo stability of hydroxyapatite labeled with 177 Lu, 90 Y and 153 Sm in order to determine the influence of the radionuclide on biological pattern. In biological studies, 100mL of labeled HAs suspended in normal saline were injected into normal knee joints of Wistar rats and the retention of the activity into the synovium was determined. Labeled particles were also injected by intravenous and intramuscular administration, to verify the biodistribution in the case of an eventual leakage of the products from the joint. Sequential scintigraphic images were acquired from 1 hour to 7 days p.i. after anesthetizing the animals with ketamine. Hydroxyapatite was radiolabeled by all radionuclides with high yield. 177 Lu-HA, 90 Y-HA and 153 Sm-HA were retained in the joint for 7 days, showing stability and usefulness as tools in the RSV treatment

  17. Synthesis of macrocyclic polyamines; complexation of basic [{sup 99m}TcO{sub 2}{sup +}] and biodistribution of complexed forms; Synthese de polyamines macrocycliques. Complexation du coeur [{sup 99m}TcO{sub 2}{sup +}] et biodistribution des complexes formes

    Energy Technology Data Exchange (ETDEWEB)

    Riche, F.; Vidal, M. [Universite Joseph Fourier, 38 - Grenoble (France); Mathieu, J.P.; Fagret, D.; Comet, M. [Universite Joseph Fourier, 38 - La Tronche (France). Faculte de Medecine; Pasqualini, R. [CIS bio international, 91 - Gif-sur-Yvette (France)

    1996-01-01

    The synthesis of macrocyclic polyamines is described, as well as their complexation with technetium via pertechnetole ligands. Several pertechnetole reducing agents were studied, as well as their method of complexation with polyamines and their charge and lipophilicity. Their biodistribution in the mouse and the dog has been studied by scintiscanning which provides evidence of their excellence as hepatobiliary tracers. (UK).

  18. Biodistribution and radiation dosimetry of [11C]DASB in baboons

    International Nuclear Information System (INIS)

    Belanger, Marie-Jose; Simpson, Norman R.; Wang, Theodore

    2004-01-01

    Objective: The serotonin transporter has been implicated in a variety of conditions including mood disorders and suicidal behavior. In vivo human brain studies with positron emission tomography and the serotonin transporter antagonist [ 11 C]DASB ([ 11 C]-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile) are ongoing in several laboratories with the maximum administered activity based on dosimetry collected in rodents. We report on the biodistribution and dosimetry of [ 11 C]DASB in the baboon as this species may be a more reliable surrogate for human dosimetry. Methods: Four baboon studies (two studies in each of two baboons) were acquired in an ECAT ACCEL camera after the bolus injection of 183±5 MBq/2.3±1.0 nmol of [ 11 C]DASB. For each study, six whole-body emission scans were collected in 3D mode over 6/7 bed positions for 2 h. Regions of interest were drawn on brain, lungs, liver, gallbladder, spleen, kidneys, small intestine and bladder. Since no fluid was removed from the animal, total body radioactivity was calculated using the injected dose calibrated to the ACCEL image units. Results: Uptake was greatest in lungs, followed by the urinary bladder, gallbladder, brain and other organs. The ligand was eliminated via the hepato-billiary and renal systems. The largest absorbed dose was found in the lungs (3.6x10 -2 mSv/MBq). The absorbed radiation doses in lungs and gallbladder were four and nine times larger than that previously estimated from rat studies. Conclusion: Based on our baboon biodistribution and dose estimates, the lungs are the critical organs for administration of [ 11 C]DASB. In the United States, the absorbed dose to the lungs would limit [ 11 C]DASB administered with the approval of a Radioactive Drug Research Committee to 1400 MBq (37 mCi) in the adult male and 1100 MBq (30 mCi) in the adult female

  19. In vivo biodistribution of CNTs using a BALB/c mouse experimental model.

    Science.gov (United States)

    Fufă, Mariana Oana Mihaela; Mihaiescu, Dan Eduard; Mogoantă, Laurenţiu; Bălşeanu, Tudor Adrian; Mogoşanu, George Dan; Grumezescu, Alexandru Mihai; Bolocan, Alexandra

    2015-01-01

    Due to their unique behaviors, carbon nanotubes (CNTs)-based systems meet essential requirements for modern applications, such as electronics, optics, photovoltaics, fuel cells, aerospace engineering, military and biomedical applications. CNTs biocompatibility and toxic effects were assessed both in vitro and in vivo, in terms of hemocompatibility, cytocompatibility, immunoreactions and genetic behavior. The aim of this paper is to evaluate the in vivo biodistribution and biocompatibility of carbon nanopowder synthesized by plasma processing, using a BALB/c mouse experimental model. Three months old BALB/c mice were aseptically injected with 100 μL of 1 mg/mL dispersions. The obtained carbon-based nano-systems were dispersed in saline solution and subsequently sterilized by using a 30 minutes treatment with UV irradiation. The reference mice were injected with 100 μL of saline. The mice were kept under standard conditions of light, temperature, humidity, food and water (ad libitum) before the vital organ harvest. The animal welfare was daily monitored. At two and 10 days after the inoculation, the animals were euthanized under general anesthesia, for the sampling of internal organs (brain, myocardium, pancreas, liver, lung, kidney and spleen). No animal died during the experiment. Brain, myocardium and pancreas were histologically normal, with no tissue damage, inflammatory infiltrate or inorganic deposits. CNTs were evidenced only in hepatic, renal, pulmonary and spleen tissue samples. Increased amounts of inorganic granular structures were reported after 10 days of treatment, when compared to the short-term (two days) inoculation. Our BALB/c mouse experimental model was found to be useful for the in vivo assessment of biodistribution and biocompatibility of CNTs.

  20. Biodistribution, pharmacokinetics and uptake ratio of 131I-4-Iodo-phenylacetic acid in normal and tumour implied animals

    International Nuclear Information System (INIS)

    Szuecs, Z.; Sello, T.; Sathekge, M.

    2012-01-01

    Complete text of publication follows. Phenyl acetate is one of the tumour metabolism compounds that is currently studied in phase II clinical trials targeting brain tumour by reducing plasma levels of glutamine. It has been reported to have a potent antiproliferative and anti-differentiating effect in haematological malignancies and in solid tumours at non-toxic concentrations. Due to the closeness of its structure compared to phenylacetic acid, as well as the reported biological activity of phenyl-acetic acid, it is hypothesized that useful information of the biodistribution of 131 I labelled agent can be obtained from experimental animals, especially with regards to its uptake in neoplastic vs normal tissue. The results presented here describe the biodistribution of 131 I-4-iodo-phenyl-acetic acid in healthy rats and nude balb c/c mice xenograft with WCHO1 cells accessing its potential as diagnostic imaging and / or therapeutic agent for the treatment of neoplastic conditions. The radiosynthesis has been described in detail earlier. It was found that the inert atmosphere and the adequate temperature are the key parameters for the synthesis. The fresh preparation of the solution of the ascorbic acid is also essential. The HPLC QC showed that the radiochemical purity of the final product was higher than 98%. The activity of the product was 96 MBq. The calculated specific activity was 355 Ci/mol. A 1 h dynamic scan was recorded for one of the rats, where after static scans were recorded for all four rats up to 5 h. From the dynamic scan fast excretion from the blood pool was visible as can be seen in Fig. 1. The time activity curves are given in Fig. 1. After completion of the scintigraphy the rats were sacrified and disected and the organs counted. The average of the percent-injected dose per gram of tissue (%ID/g) was determined. The xenograft mice were sacrified after 5h after injection and disected and the organs counted. The average of the percent-injected dose

  1. Biodistribution, binding specificity and metabolism of [{sup 18}F]fluoroethylflumazenil in rodents

    Energy Technology Data Exchange (ETDEWEB)

    Leveque, Philippe; Labar, Daniel; Gallez, Bernard E-mail: gallez@cmfa.ucl.ac.be

    2001-10-01

    Pre-clinical studies were carried out in order to characterize in rodents the biodistribution, the binding specificity and the metabolism of [{sup 18}F]Fluoroethylflumazenil ([{sup 18}F]FEF), a potential candidate for in vivo imaging of the benzodiazepine receptors. In vivo competition with flumazenil indicates that [{sup 18}F]FEF binds specifically to the benzodiazepine receptor in the brain. The accumulation of [{sup 18}F]FEF was significantly lower than using [{sup 3}H]Flumazenil. The rather low accumulation in the brain is due to a rapid metabolism of [{sup 18}F]FEF in hydrophylic metabolites which cannot cross the blood brain barrier, and are rapidly eliminated in the urine. Inhibition of the metabolism by acetaminophen (chemically induced hepatitis) led to a significant increase of the radioactivity found in the circulating blood and in the brain, while these results were not observed using classical inhibitors of the cytochrome CYP450, cimetidine and ketoconazole.

  2. Preparation, radiochemical analysis and biodistribution of 99mTc-dihydrobis(1-pyrazolyl)borate

    International Nuclear Information System (INIS)

    Owunwanne, A.; Abdel-Dayem, H.; Yacoub, T.

    1987-01-01

    Optimum preparation of 99m Tc-dihydrobis(1-pyrazolyl)borate ( 99m Tc-HBPz 2 ) was done by mixing 1.4 mg/ml HBPz 2 and 1.0 mg/ml of stanous PYP. Radiochemical analysis of the preparation using paper chromatography (PC), thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) indicated a stable product with one major component. The labelling efficiency was approximately 90%. Animal biodistribution studies performed in mice showed that most of the injected radioactivity was confined to the liver, kidney, lungs, intestine and heart. The heart to blood ratio was small but persisted up to 3 hrs. after the injection. (orig.) [de

  3. The Noah's Ark experiment: species dependent biodistributions of cationic 99mTc complexes

    International Nuclear Information System (INIS)

    Deutsch, Edward; Ketring, A.R.; Libson, Karen; Vanderheyden, J.-L.; Hirth, W.W.

    1989-01-01

    The time dependent biodistributions of three related 99m Tc complexes of 1, 2-bis(dimethylphosphino)ethane (DMPE) were evaluated in several animal species including humans: trans-[ 99m Tc v (DMPE) 2 O 2 ] + , trans-[ 99m Tc III (DMPE) 2 Cl 2 ] + and [ 99m Tc I (DMPE) 3 ] + . Imaging studies were performed in 10 animal species to evaluate these complexes as myocardial perfusion imaging agents. Animal models adequately predict the uninteresting behaviour of the Tc(V) cation in humans, predict to only a very limited extent the behaviour of the Tc(III) cation in humans and totally fail to predict the behaviour of the Tc(I) cation in humans. (U.K.)

  4. Preparation and biodistribution of {sup 59}Fe-radiolabelled iron oxide nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Pospisilova, Martina, E-mail: martinapospisilova@gmail.com; Zapotocky, Vojtech; Nesporova, Kristina [Contipro a.s (Czech Republic); Laznicek, Milan; Laznickova, Alice [Charles University, Faculty of Pharmacy in Hradec Králové (Czech Republic); Zidek, Ondrej; Cepa, Martin; Vagnerova, Hana; Velebny, Vladimir [Contipro a.s (Czech Republic)

    2017-02-15

    We report on the {sup 59}Fe radiolabelling of iron oxide nanoparticle cores through post-synthetic isotope exchange ({sup 59}Fe-IONP{sub ex}) and precursor labelling ({sup 59}Fe-IONP{sub pre}). Scanning electron microscopy and dynamic light scattering measurements showed no impact of radiolabelling on nanoparticle size or morphology. While incorporation efficiencies of these methods are comparable—83 and 90% for precursor labelling and post-synthetic isotope exchange, respectively—{sup 59}Fe-IONP{sub pre} exhibited much higher radiochemical stability in citrated human plasma. Quantitative ex vivo biodistribution study of {sup 59}Fe-IONP{sub pre} coated with triethylene glycol was performed in Wistar rats. Following the intravenous administration, high {sup 59}Fe concentration was observed in the lung and the organs of the reticuloendothelial system such as the liver, the spleen and the femur.

  5. Synthesis and biodistribution of 99mTc-Vancomycin in a model of bacterial infection

    International Nuclear Information System (INIS)

    Roohi, S.; Mushtaq, A.; Malik, S.A.

    2005-01-01

    Vancomycin Hydrochloride is an antibiotic produced by the growth of certain strains of Streptomyces orientalis. As vancomycin hydrochloride is poorly absorbed after oral administration; it is given intravenously for therapy of systemic infections. Vancomycin was labeled with technetium-99m pertechnetate using SnCl 2 . 2H 2 O as reducing agent. The labeling efficiency depends on ligand/reductant ratio, pH, and volume of reaction mixture. Radiochemical purity and stability of 99m Tc-Vancomycin was determined by thin layer chromatography. Biodistribution studies of 99m Tc-Vancomycin were performed in a model of bacterial infection in Sprague-Dawley rats. A significantly higher accumulation of 99m Tc-Vancomycin was seen at sites of S. aureus infected animals. Whereas uptake of 99m Tc-Vancomycin in turpentine inflamed rats were quite low. (orig.)

  6. Stabilization of neurotensin analogues: effect on peptide catabolism, biodistribution and tumor binding

    Energy Technology Data Exchange (ETDEWEB)

    Bruehlmeier, Matthias E-mail: peter.blaeuenstein@psi.ch; Garayoa, Elisa Garcia; Blanc, Alain; Holzer, Barbara; Gergely, Suzanne; Tourwe, Dirk; Schubiger, Pius August; Blaeuenstein, Peter

    2002-04-01

    Neurotensin (NT) receptors in pancreatic and other neuroendocrine tumors are promising targets for imaging and therapeutic purposes. Here, we report on the effect of distinct changes in the peptide chain on catabolism in vitro for five radiolabeled [{sup 99m}Tc] neurotensin analogues having high affinity for neurotensin receptors. Substitution of NT(1-7) by (N{alpha}His)Ac--the Tc-binding moiety--combined with a reduced bond 8-9 (CH{sub 2}NH), N-methylation of peptide bonds or replacement of Ile(12) by tertiary leucin (Tle) led to peptide stabilization of various degrees. Biodistribution studies in nude mice bearing HT29 xenografts showed higher tumor uptake with more stable peptides, yielding high tumor to blood ratios of up to 70.

  7. Biodistribution mechanisms of therapeutic monoclonal antibodies in health and disease.

    Science.gov (United States)

    Tabrizi, Mohammad; Bornstein, Gadi Gazit; Suria, Hamza

    2010-03-01

    The monoclonal antibody market continues to witness an impressive rate of growth and has become the leading source of expansion in the biologic segment within the pharmaceutical industry. Currently marketed monoclonal antibodies target a diverse array of antigens. These antigens are distributed in a variety of tissues such as tumors, lungs, synovial fluid, psoriatic plaques, and lymph nodes. As the concentration of drug at the proximity of the biological receptor determines the magnitude of the observed pharmacological responses, a significant consideration in effective therapeutic application of monoclonal antibodies is a thorough understanding of the processes that regulate antibody biodistribution. Monoclonal antibody distribution is affected by factors such as molecular weight, blood flow, tissue and tumor heterogeneity, structure and porosity, target antigen density, turnover rate, and the target antigen expression profile.

  8. Biodistribution and tolerance of intravenous iodine-131-labelled hypericin in healthy dogs.

    Science.gov (United States)

    Abma, E; Peremans, K; De Vos, F; Bosmans, T; Kitshoff, A M; Daminet, S; Ni, Y; Dockx, R; de Rooster, H

    2018-01-04

    Hypericin (Hyp) is a necrosis-avid compound that can be efficiently labelled with radioiodine for both diagnostic and therapeutic purposes. Before 131 I-Hyp can be considered as a clinically useful drug in a combination therapy for canine cancer patients, evaluation of its toxicity is necessary. The aim of this study was to investigate the biodistribution and tolerance of a single dose administration of 131 I-Hyp. Three healthy dogs were included. 131 I-Hyp at a dose of 0.2 mg/kg and an activity of 185 MBq was intravenously injected. The effects on physical, haematological and biochemical parameters were characterized and the biodistribution and elimination pattern, the effective half-life and dose rate were assessed. Drug-related adverse events were limited to mild gastrointestinal signs, resolving within 48 hours. No significant differences were found in blood haematology and serum biochemistry before and after treatment. Following administration, highest percentage of injected dose (%ID ± SD) was found in the liver (5.5 ± 0.33), the lungs (4.17 ± 0.14) and the heart (3.11 ± 0.78). After 24 hours, highest %ID was found in colon (4.25 ± 1.45) and liver (3.45 ± 0.60). Clearance from all organs was effective within 7 days. Effective half-life was established at 80 hours, and the dose rate fell below <20 μSv/h at 1 m within 1 day. The current study reveals that single dose treatment with 131 I-Hyp at the described dose is well tolerated by healthy dogs and supports the use of radioiodinated hypericin in a combination therapy for canine cancer patients. © 2018 John Wiley & Sons Ltd.

  9. Biodistribution of ultra small superparamagnetic iron oxide nanoparticles in BALB mice

    International Nuclear Information System (INIS)

    Saeed Shanehsazzadeh; Mohammad Ali Oghabian; Tehran University of Medical Science, Tehran; Fariba Johari Daha; Massoud Amanlou; Allen, B.J.

    2013-01-01

    Recently ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles (NPs) have been widely used for medical applications. One of their important applications is using these particles as MRI contrast agent. While various research works have been done about MRI application of USPIOs, there is limited research about their uptakes in various organs. The aim of this study was to evaluate the biodistribution of dextran coated iron oxide NPs labelled with 99m Tc in various organs via intravenous injection in Balb/c mice. The magnetite NPs were dispersed in phosphate buffered saline and SnCl 2 which was used as a reduction reagent. Subsequently, the radioisotope 99m Tc was mixed directly into the reaction solution. The labeling efficiency of USPIOs labeled with 99m Tc, was above 99 %. Sixty mice were sacrificed at 12 different time points (From 1 min to 48 h post injections; five mice at each time). The percentage of injected dose per gram of each organ was measured by direct counting for 19 harvested organs of the mice. The biodistribution of 99m Tc-USPIO in Balb/c mice showed dramatic uptake in reticuloendothelial system. Accordingly, about 75 percent of injected dose was found in spleen and liver at 15 min post injection. More than 24 % of the NPs remain in liver after 48 h post-injection and their clearance is so fast in other organs. The results suggest that USPIOs as characterized in our study can be potentially used as contrast agent in MR Imaging, distributing reticuloendothelial system specially spleen and liver. (author)

  10. Intranasal haloperidol-loaded miniemulsions for brain targeting: Evaluation of locomotor suppression and in-vivo biodistribution.

    Science.gov (United States)

    El-Setouhy, Doaa Ahmed; Ibrahim, A B; Amin, Maha M; Khowessah, Omneya M; Elzanfaly, Eman S

    2016-09-20

    Haloperidol is a commonly prescribed antipsychotic drug currently administered as oral and injectable preparations. This study aimed to prepare haloperidol intranasal miniemulsion helpful for psychiatric emergencies and exhibiting lower systemic exposure and side effects associated with non-target site delivery. Haloperidol miniemulsions were successfully prepared by spontaneous emulsification adopting 2(3) factorial design. The effect of three independent variables at two levels each namely; oil type (Capmul®-Capryol™90), lipophilic emulsifier type (Span 20-Span 80) and HLB value (12-14) on globule size, PDI and percent locomotor activity inhibition in mice was evaluated. The optimized formula (F4, Capmul®, Tween 80/Span 20, HLB 14) showed globule size of 209.5±0.98nm, PDI of 0.402±0.03 and locomotor inhibition of 83.89±9.15% with desirability of 0.907. Biodistribution study following intranasal and intravenous administration of the radiolabeled (99m)Tc mucoadhesive F4 revealed that intranasal administration achieved 1.72-fold higher and 6 times faster peak brain levels compared with intravenous administration. Drug targeting efficiency percent and brain/blood exposure ratios remained above 100% and 1 respectively after intranasal instillation compared to a maximum brain/blood exposure ratio of 0.8 post intravenous route. Results suggested the CNS delivery of major fraction of haloperidol via direct transnasal to brain pathway that can be a promising alternative to oral and parenteral routes in chronic and acute situations. Haloperidol concentration of 275.6ng/g brain 8h post intranasal instillation, higher than therapeutic concentration range of haloperidol (0.8 to 5.15ng/ml), suggests possible sustained delivery of the drug through nasal route. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. Biodistribution and tumor imaging of an anti-CEA single-chain antibody-albumin fusion protein

    International Nuclear Information System (INIS)

    Yazaki, Paul J.; Kassa, Thewodros; Cheung, Chia-wei; Crow, Desiree M.; Sherman, Mark A.; Bading, James R.; Anderson, Anne-Line J.; Colcher, David; Raubitschek, Andrew

    2008-01-01

    Albumin fusion proteins have demonstrated the ability to prolong the in vivo half-life of small therapeutic proteins/peptides in the circulation and thereby potentially increase their therapeutic efficacy. To evaluate if this format can be employed for antibody-based imaging, an anticarcinoembryonic antigen (CEA) single-chain antibody(scFv)-albumin fusion protein was designed, expressed and radiolabeled for biodistribution and imaging studies in athymic mice bearing human colorectal carcinoma LS-174T xenografts. The [ 125 I]-T84.66 fusion protein demonstrated rapid tumor uptake of 12.3% injected dose per gram (ID/g) at 4 h that reached a plateau of 22.7% ID/g by 18 h. This was a dramatic increase in tumor uptake compared to 4.9% ID/g for the scFv alone. The radiometal [ 111 In]-labeled version resulted in higher tumor uptake, 37.2% ID/g at 18 h, which persisted at the tumor site with tumor: blood ratios reaching 18:1 and with normal tissues showing limited uptake. Based on these favorable imaging properties, a pilot [ 64 Cu]-positron emission tomography imaging study was performed with promising results. The anti-CEA T84.66 scFv-albumin fusion protein demonstrates highly specific tumor uptake that is comparable to cognate recombinant antibody fragments. The radiometal-labeled version, which shows lower normal tissue accumulation than these recombinant antibodies, provides a promising and novel platform for antibody-based imaging agents

  12. Biodistribution and radiation dosimetry of {sup 11}C-labelled docetaxel in cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Veldt, Astrid A.M. van der; Mooijer, Martien P.J.; Rijnders, Anneloes Y.; Windhorst, Albert D.; Lammertsma, Adriaan A.; Lubberink, Mark [VU University Medical Center, Department of Nuclear Medicine and PET Research, P.O. Box 7057, Amsterdam (Netherlands); Hendrikse, N.H. [VU University Medical Center, Department of Nuclear Medicine and PET Research, P.O. Box 7057, Amsterdam (Netherlands); VU University Medical Center, Department of Clinical Pharmacology and Pharmacy, Amsterdam (Netherlands); Smit, Egbert F. [VU University Medical Center, Department of Pulmonology, Amsterdam (Netherlands); Gerritsen, Winald R. [VU University Medical Center, Department of Medical Oncology, Amsterdam (Netherlands); Hoeven, Jacobus J.M. van der [Medical Center Alkmaar, Department of Internal Medicine, Alkmaar (Netherlands)

    2010-10-15

    Docetaxel is an important chemotherapeutic agent used for the treatment of several cancer types. As radiolabelled anticancer agents provide a potential means for personalized treatment planning, docetaxel was labelled with the positron emitter {sup 11}C. Non-invasive measurements of [{sup 11}C]docetaxel uptake in organs and tumours may provide additional information on pharmacokinetics and pharmacodynamics of the drug docetaxel. The purpose of the present study was to determine the biodistribution and radiation absorbed dose of [{sup 11}C]docetaxel in humans. Biodistribution of [{sup 11}C]docetaxel was measured in seven patients (five men and two women) with solid tumours using PET/CT. Venous blood samples were collected to measure activity in blood and plasma. Regions of interest (ROI) for various source organs were defined on PET (high [{sup 11}C]docetaxel uptake) or CT (low [{sup 11}C]docetaxel uptake). ROI data were used to generate time-activity curves and to calculate percentage injected dose and residence times. Radiation absorbed doses were calculated according to the MIRD method using OLINDA/EXM 1.0 software. Gall bladder and liver demonstrated high [{sup 11}C]docetaxel uptake, whilst uptake in brain and normal lung was low. The percentage injected dose at 1 h in the liver was 47 {+-} 9%. [{sup 11}C]docetaxel was rapidly cleared from plasma and no radiolabelled metabolites were detected. [{sup 11}C]docetaxel uptake in tumours was moderate and highly variable between tumours. The effective dose of [{sup 11}C]docetaxel was 4.7 {mu}Sv/MBq. As uptake in normal lung is low, [{sup 11}C]docetaxel may be a promising tracer for tumours in the thoracic region. (orig.)

  13. The biodistribution and radiation dosimetry of 99Tcmm-EC-DG in normal volunteers

    International Nuclear Information System (INIS)

    Tang Jun; Yang Yi; Liu Zengli; Shi Yizhen

    2010-01-01

    <