Study of the demand for radiopharmaceutical 18F-FDG in the metropolitan regions of Sao Paulo and adjacent areas

International Nuclear Information System (INIS)

Sato, Renato Cesar

2006-01-01

Nuclear Medicine in Brazil and worldwide has developed distinction with diagnosis techniques that allow metabolic research of the disease, changing in a significant fashion the patient's outcome. This innovative technology leads expectations from specific fields up to society itself. This research studied the use of 18 F-FDG radiopharmaceutical in the metropolitan region of Sao Paulo and adjacent areas, as well as the recent trade structure and the difficulties that should be overcome with the increase of the 18 F-FDG demand. This research counted on the analysis of the international radiopharmaceutical trade and the main changes that have been happening in this area in Brazil during the past few years. Interviews were performed with professionals within the area of nuclear medicine and data has been collected through questionnaire sent to the consuming centers of the radiopharmaceutical in the region covered in this research. The interviews expressed the opinions of the interviewees concerning transformations in this field and future tendencies and the information obtained from the survey was the basis of complementation of the use of radiopharmaceutical on equipment such as Single Photon Emission Computed Tomography (SPECT), Positron Emission Tomography (PET) and Positron Emission Tomography I Computer Tomography (PET/CT). The major use of 18 F-FDG has been used for oncology diagnosis with equipment such as PET and PEC/CT. This use shall grow in the next years, maybe expanding to other specialties such as neurology and cardiology. Although nowadays restricted to the cities of Sao Paulo and Rio de Janeiro, there is a possibility of expansion to other diagnosis modalities in other states of the country that are starting to structure the production of the radioisotope. The recent change in the constitution permitting the production and commerce of short half-life radioisotopes also contributes to the increase the interest of private funding of this sector in which

DOE SBIR Phase I Grant No. DE-FG02-00ER83067, ''A Flexible and Economical Automated Nucleophilic [18F]Fluorination synthesis System for PET Radiopharmaceuticals.'' Final Technical Report

International Nuclear Information System (INIS)

Padgett, Henry C.

2001-01-01

Phase I Final Report. A prototype manual remote synthesis system based on the unit operations approach was designed, constructed, and functionally tested. This general-purpose system was validated by its configuration and initial use for the preparation of the PET radiopharmaceutical [F-18]FLT using [F-18]fluoride ion

Activity-based costing evaluation of [18F]-fludeoxyglucose production.

Science.gov (United States)

Krug, Bruno; Van Zanten, Annie; Pirson, Anne-Sophie; Crott, Ralph; Vander Borght, Thierry

2008-01-01

As healthcare expenses are escalating in many countries, the sector faces a new challenge of becoming more cost efficient. There is an urgent need for more accurate data on the costs of healthcare procedures. The cost of Positron Emission Tomography (PET) with [(18)F]-fludeoxyglucose ((18)F-FDG) studies is mainly influenced by the price of the radiopharmaceutical, which may vary throughout Europe from 300 to 500 Euro per patient dose (370 MBq). The aim of the current study is to conduct an activity-based costing (ABC) estimation of (18)F-FDG production in Europe to better identify the different cost components and to analyse their relative contribution to the total cost. Financial data were collected on capital expense and global operating costs through interviews with industry experts, PET centre managers, evaluation of prior studies, and review of expenses incurred at the University Medical Centre in Groningen (The Netherlands). After mapping the activities, we divided the cost in five categories: wage, equipment, consumables, overhead and space costs. A sensitivity analysis was performed for key cost components, including the compliance with regulatory requirements. The critical factor for profitability was throughput. Including the European regulation procedure, the cost for 370 MBq (18)F-FDG patient dose, 3 h EOS without delivery cost, ranges between 155 and 177 Euro/dose for two production runs and between 210 and 237 Euro/dose for one production run. These costs are predominantly determined by personnel and equipment costs, although the cost for quality assurance increases steadily. The ABC analysis provides significant insight into the production cost components of (18)F-FDG through different operating configurations. Reductions in equipment prices, increased availability of radiopharmaceuticals, growth in demand, and improvements in reimbursement will all contribute to the financial viability of this imaging technique.

Activity-based costing evaluation of [18F]-fludeoxyglucose production

International Nuclear Information System (INIS)

Krug, Bruno; Pirson, Anne-Sophie; Borght, Thierry vander; Zanten, Annie van; Crott, Ralph

2008-01-01

As healthcare expenses are escalating in many countries, the sector faces a new challenge of becoming more cost efficient. There is an urgent need for more accurate data on the costs of healthcare procedures. The cost of Positron Emission Tomography (PET) with [ 18 F]-fludeoxyglucose ( 18 F-FDG) studies is mainly influenced by the price of the radiopharmaceutical, which may vary throughout Europe from 300 to 500 Euro per patient dose (370 MBq). The aim of the current study is to conduct an activity-based costing (ABC) estimation of 18 F-FDG production in Europe to better identify the different cost components and to analyse their relative contribution to the total cost. Financial data were collected on capital expense and global operating costs through interviews with industry experts, PET centre managers, evaluation of prior studies, and review of expenses incurred at the University Medical Centre in Groningen (The Netherlands). After mapping the activities, we divided the cost in five categories: wage, equipment, consumables, overhead and space costs. A sensitivity analysis was performed for key cost components, including the compliance with regulatory requirements. The critical factor for profitability was throughput. Including the European regulation procedure, the cost for 370 MBq 18 F-FDG patient dose, 3 h EOS without delivery cost, ranges between 155 and 177 Euro/dose for two production runs and between 210 and 237 Euro/dose for one production run. These costs are predominantly determined by personnel and equipment costs, although the cost for quality assurance increases steadily. The ABC analysis provides significant insight into the production cost components of 18 F-FDG through different operating configurations. Reductions in equipment prices, increased availability of radiopharmaceuticals, growth in demand, and improvements in reimbursement will all contribute to the financial viability of this imaging technique. (orig.)

F-18 labelling agents

International Nuclear Information System (INIS)

Mikecz, P.

2001-01-01

In this presentation the production of fluorine-18, separation of [ 18 F]fluoride, converting fluoride into fluorine as well as fluorine incorporation into organic molecules are reviewed. Reaction schemes and technology schemes are included. Towards organic reactions, with help of small molecules of the 18 F can be introduced into a wide variety of radiopharmaceuticals. (author)

Yields of nuclear reactions for the production of radiopharmaceuticals 18F, 43K, 67Ga, 111In and 123I with charged particles

International Nuclear Information System (INIS)

Bem, P.; Burjan, V.; Schaferlingova, W.; Vincour, J.; Kopecky, P.

1977-02-01

Experimental results are given of reaction yields in the preparation of radiopharmaceuticals ( 18 F, 43 K, 67 Ga, 111 In, 123 I) using common cyclotron beams, i.e., proton beams, deuteron beams, 3 He and alpha particles in an energy range of up to several MeV/nucleon. A detailed analysis is made of the choice of suitable target materials for the production of the above radiopharmaceuticals with regard to the economical use of the accelerator and of the purity of the radiopharmaceuticals prepared. (I.W.)

Acute and subacute toxicity of {sup 18}F-FDG; Toxicidade aguda e subaguda do radiofarmaco {sup 18}F-FDG

Energy Technology Data Exchange (ETDEWEB)

Dantas, Danielle Maia

2013-07-01

Before starting clinical trials of a new drug, it is necessary to perform a battery of safety tests for assessing human risk. Radiopharmaceuticals like any new drug must be tested taking into account its specificity, duration of treatment and especially the toxicity of both parties, the unlabeled molecule and its radionuclide, apart from impurities emanating from radiolysis. Regulatory agencies like the Food and Drug Administration - USA (FDA) and the European Medicine Agency (EMEA), establish guidelines for the regulation of production and research of radiopharmaceuticals. In Brazil the production of radiopharmaceuticals was not regulated until the end of 2009, when were established by the National Agency for Sanitary Surveillance (ANVISA) resolutions No. 63, which refers to the Good Manufacturing Practices of Radiopharmaceuticals and No. 64 which seeks the registration of record radiopharmaceuticals. To obtain registration of radiopharmaceuticals are necessary to prove the quality, safety, efficacy and specificity of the drug . For the safety of radiopharmaceuticals must be presented studies of acute toxicity, subacute and chronic toxicity as well as reproductive, mutagenic and carcinogenic. Nowadays IPEN-CNEN/SP produces one of the most important radiopharmaceutical of nuclear medicine, the {sup 18}F-FDG, which is used in many clinical applications, particularly in the diagnosis and staging of tumors. The objective of this study was to evaluate the systemic toxicity (acute/ subacute) radiopharmaceutical {sup 18}F-FDG in an in vivo test system, as recommended by the RDC No. 64, which will serve as a model for protocols toxicity of radiopharmaceuticals produced at IPEN. The following tests were performed: tests of acute and subacute toxicity, biodistribution studies of {sup 18}F-FDG, comet assay and reproductive toxicity. In acute toxicity, healthy rats were injected . (author)

18F-FET and 18F-FCH uptake in human glioblastoma T98G cell lines

International Nuclear Information System (INIS)

Persico, Marco Giovanni; Buroni, Federica Eleonora; Pasi, Francesca; Lodola, Lorenzo; Aprile, Carlo; Nano, Rosanna; Hodolic, Marina

2016-01-01

Despite complex treatment of surgery, radiotherapy and chemotherapy, high grade gliomas often recur. Differentiation between post-treatment changes and recurrence is difficult. 18 F-methyl-choline ( 18 F-FCH) is frequently used in staging and detection of recurrent prostate cancer disease as well as some brain tumours; however accumulation in inflammatory tissue limits its specificity. The 18 F-ethyl-tyrosine ( 18 F-FET) shows a specific uptake in malignant cells, resulting from increased expression of amino acid transporters or diffusing through the disrupted blood-brain barrier. 18 F-FET exhibits lower uptake in machrophages and other inflammatory cells. Aim of this study was to evaluate 18 F-FCH and 18 F-FET uptake by human glioblastoma T98G cells. Human glioblastoma T98G or human dermal fibroblasts cells, seeded at a density to obtain 2 × 10 5 cells per flask when radioactive tracers were administered, grew adherent to the plastic surface at 37°C in 5% CO 2 in complete medium. Equimolar amounts of radiopharmaceuticals were added to cells for different incubation times (20 to 120 minutes) for 18 F-FCH and 18 F-FET respectively. The cellular radiotracer uptake was determined with a gamma counter. All experiments were carried out in duplicate and repeated three times. The uptake measurements are expressed as the percentage of the administered dose of tracer per 2 × 10 5 cells. Data (expressed as mean values of % uptake of radiopharmaceuticals) were compared using parametric or non-parametric tests as appropriate. Differences were regarded as statistically significant when p<0.05. A significant uptake of 18 F-FCH was seen in T98G cells at 60, 90 and 120 minutes. The percentage uptake of 18 F-FET in comparison to 18 F-FCH was lower by a factor of more than 3, with different kinetic curves. 18 F-FET showed a more rapid initial uptake up to 40 minutes and 18 F-FCH showed a progressive rise reaching a maximum after 90 minutes. 18 F-FCH and 18 F-FET are candidates

Study of the production of the radiopharmaceutical {sup 18}F-FLT in automated system: contribution for process validation; Estudo da producao do radiofarmaco FLT-{sup 18}F em sistema automatizado: contribuicao para a validacao do processo

Energy Technology Data Exchange (ETDEWEB)

Zanette, Camila

2013-07-01

Radiopharmaceutical {sup 18}F-FLT is a thymidine nucleoside analogue and a promising tumor proliferation marker for PET images. The synthesis of this radiopharmaceutical is not simple, and often has low yields. This radiopharmaceutical has already been studied for some years; however, there is no production, nor are there clinical studies in Brazil. The study of the production process and its compliance with the guidelines of Good Manufacturing Practices (ANVISA) are of extreme importance. This study aimed to investigate the synthesis of this radiopharmaceutical, evaluate methods of quality control that will be used in future production routines, perform cytotoxicity studies, biodistribution studies and PET imaging in animals, thereby contributing to the development and elaboration of the process validation protocol and to the establishment of analytical methods to be used during production routines. Initially, we studied the synthesis and production of {sup 18}F-FLT, with the evaluation of three different temperatures of radiolabeling to check the behavior of the radiochemical yield and stability of the nal product. Studies of analytical methodology comprised the analysis of radionuclide identification, determination of chromatographic profiles, radiochemical purity, residual solvents, and pH. In vitro studies of internalization and cytotoxicity were also carried out. In in vivo studies, we evaluated the pharmacokinetics, biodistribution in healthy animals and in animals with tumor models, in addition to PET/CT images in animals with melanomas. The final product had high radiochemical purity and was stable for up to 10 hours after the synthesis, but got a relatively low radiochemical yield, as described in the literature. The tested analytical methods proved suitable for use in the quality control of {sup 18}F-FLT. In in vitro studies, {sup 18}F-FLT showed a significant percentage of binding to tumor cells, and the nonradiolabeled molecule was not considered toxic

Acute and subacute toxicity of 18F-FDG

International Nuclear Information System (INIS)

Dantas, Danielle Maia

2013-01-01

Before starting clinical trials of a new drug, it is necessary to perform a battery of safety tests for assessing human risk. Radiopharmaceuticals like any new drug must be tested taking into account its specificity, duration of treatment and especially the toxicity of both parties, the unlabeled molecule and its radionuclide, apart from impurities emanating from radiolysis. Regulatory agencies like the Food and Drug Administration - USA (FDA) and the European Medicine Agency (EMEA), establish guidelines for the regulation of production and research of radiopharmaceuticals. In Brazil the production of radiopharmaceuticals was not regulated until the end of 2009, when were established by the National Agency for Sanitary Surveillance (ANVISA) resolutions No. 63, which refers to the Good Manufacturing Practices of Radiopharmaceuticals and No. 64 which seeks the registration of record radiopharmaceuticals. To obtain registration of radiopharmaceuticals are necessary to prove the quality, safety, efficacy and specificity of the drug . For the safety of radiopharmaceuticals must be presented studies of acute toxicity, subacute and chronic toxicity as well as reproductive, mutagenic and carcinogenic. Nowadays IPEN-CNEN/SP produces one of the most important radiopharmaceutical of nuclear medicine, the 18 F-FDG, which is used in many clinical applications, particularly in the diagnosis and staging of tumors. The objective of this study was to evaluate the systemic toxicity (acute/ subacute) radiopharmaceutical 18 F-FDG in an in vivo test system, as recommended by the RDC No. 64, which will serve as a model for protocols toxicity of radiopharmaceuticals produced at IPEN. The following tests were performed: tests of acute and subacute toxicity, biodistribution studies of 18 F-FDG, comet assay and reproductive toxicity. In acute toxicity, healthy rats were injected . (author)

HPLC-MS technique in radiopharmaceutical research (the quality control of 18F-2-fluorodeoxyglucose as an example)

International Nuclear Information System (INIS)

Macasek, F.

2001-01-01

Application of radiopharmaceuticals puts increasing demands on their quality control, considering the short half-times, high specific activities (auto-radiolytic effects), and general quality (chemical purity, apyrogenity and sterility) of pharmacy. Mostly, the radioanalytical control consists of application of several separation and instrumental analytical techniques. In this paper, perspective of the hyphenated HPLC and MS techniques is demonstrated on the example of one of the most spread radiopharmaceutical, 2-[ 18 F]fluoro-2-deoxy-D-glucose (further as FDG). In this work, a liquid chromatography/refractive index detector/radiometric detector/mass spectrometric detector combination (HPLC/RID/RAD/MSD) was used for development of a complex routine technique. Optimization of HPLC/MS analysis was performed investigating the electrospray ionization (ESI) analytical signal of mass spectrometer as a function of various eluent composition (see this book, p. 39). Some results, illustrating the glucose and FDG ESI-MS, and also composition of FDG after autoradiolysis, which were obtained either by a TOF Mariner (Perkin Elmer) mass-spectrometer and Agilent 1100 HPLC-MS equipment with quadrupole MS detector are discussed. They give evidence of admixtures and radiolytic formation of deoxyglucose, deoxychloroglucose, erythrose, erytritol, gluconic acid, lactose, raffinose, saccharic acid, sorbitol/[ 19 F]FDG, xylitol, and also univalent ions of C 6 H 10 O 7 F.H 2 O and C 6 H 12 O 8 compounds. The results indicate that the emerging demands on radiopharmaceuticals quality control can be fulfilled in-time only by the radio-HPLC technique developed by the help of a tandem mass-spectrometric detector. (authors)

Biological distribution of [18F-FDG] using reactor produced [18F

International Nuclear Information System (INIS)

Sierralta, P.; Massardo, T; Gil, M.C; Gonzalez, P; Chandia, M.; Godoy, N.; Troncoso, F

2002-01-01

The animal model that relates biodistribution of a substance is fundamental prior to using it in human beings. For the evaluation of myocardial viability after a recent MI, the use of reactor produced [ 18 F]-FDG (a radiotracer usually obtained in Cyclotron) is proposed, production of which has never been attempted in our country. Specific Activities founded in the different tissues after injection of this radiotracer in an animal model were compared with those obtained by other authors with cyclotron [ 18 F]-FDG. No statistically significant differences in the critical organs were found. Hence, reactor produced [ 18 F]-FDG is a useful radiopharmaceutical in cardiac cellular metabolism assessment (author)

One of the problems of radiation protection in nuclear medicine: hand skin irradiation of the of workers in selected activities with radiopharmaceutical 18F-FDG

International Nuclear Information System (INIS)

Hudzietzova, J.; Sabol, J.; Fueloep, M.

2014-01-01

The paper deals with the evaluation of local irradiation of hand skin of the personnel of selected PET department on the basis of experimental measurements with TLD. Activities were considered during manipulation with a radiopharmaceutical 18 F-labeled radionuclide (radiopharmaceutical preparation and application). The paper also discussed the effects on the size of the local hand skin irradiation including the possibilities of reducing them. (authors)

New radiopharmaceuticals

International Nuclear Information System (INIS)

Payoux, P.; Esquerre, J.P.; Alonso, M.; Tafani, M.

2008-01-01

With the development of positron emission tomography, the significant increase in prescriptions of [ 18 F]F.D.G. has underlined the interest for molecular imaging in many pathologies. Facing the demand of 'new' radiopharmaceuticals (frequently clinically validated in the last century) for more and more specific diagnosis, the nuclear physician is confronted with a sparse offer of the radiopharmaceutical companies and a particularly complicated radiopharmaceutical legislation. This paper briefly reports on the radiopharmaceutical statutes encountered in France nowadays; it emphasizes that is essential to deeply modify the conditions to obtain a marketing authorization for radiopharmaceuticals if we want to propose to our patients the kind of right they have to expect from nuclear medicine. (authors)

Biological distribution of [{sup 18}F-FDG] using reactor produced [{sup 18}F]; Distribucion biologica del {sup 18}F-Fluordeoxiglucosa utilizando [{sup 18}F] producido en reactor

Energy Technology Data Exchange (ETDEWEB)

Sierralta, P; Massardo, T [Centro de Medicina Nuclear. Hospital Clinico Universidad de Chile, Santiago (Chile); Gil, M C [CGM Nuclear, Santiago (Chile); Gonzalez, P [Centro de Medicina Nuclear. Hospital Clinico Universidad de Chile, Santiago (Chile); Chandia, M; Godoy, N; Troncoso, F [Comision Chilena de Energia Nuclear, Cen La Reina, Santiago (Chile)

2002-12-01

The animal model that relates biodistribution of a substance is fundamental prior to using it in human beings. For the evaluation of myocardial viability after a recent MI, the use of reactor produced [{sup 18}F]-FDG (a radiotracer usually obtained in Cyclotron) is proposed, production of which has never been attempted in our country. Specific Activities founded in the different tissues after injection of this radiotracer in an animal model were compared with those obtained by other authors with cyclotron [{sup 18}F]-FDG. No statistically significant differences in the critical organs were found. Hence, reactor produced [{sup 18}F]-FDG is a useful radiopharmaceutical in cardiac cellular metabolism assessment (author)

Do the metabolites of 6-[F-18]fluoro-L-dopa and of [F-18]fluoro-meta-L-tyrosine contribute to the F-18 accumulation in the human brain?

International Nuclear Information System (INIS)

Firnau, G.; Chirakal, R.; Nahmias, C.; Garnett, E.S.

1990-01-01

The purpose of this study was to determine if the metabolites of 6-[F-18]fluoro-L-dopa (F-dopa) and of [F-18]fluoro-meta-L-tyrosine (FmLtyr) contribute to the accumulation of fluorine-18 in the brain through unspecific retention. PET studies were conducted on a healthy human subject who was treated with both of the radiopharmaceuticals and their labelled metabolites. Results indicated that in contrast to F-dopa, the metabolite of FmLtyr does not 'contaminate' the brain with extraneous fluorine-18

Positron emitting nuclides and their synthetic incorporation in radiopharmaceuticals. [Labeled with /sup 11/C, /sup 13/N, and /sup 18/F

Energy Technology Data Exchange (ETDEWEB)

Fowler, J.S.

1976-01-01

/sup 11/C, /sup 13/N, and /sup 15/O has potential applicability to the study of metabolism in humans. Problems in the synthesis of radiopharmaceuticals labeled with /sup 11/C, /sup 13/N, and /sup 18/F are described: quality control, radiation exposure, carboxylic acids, glucose, amines, amino acids, nitrosources, fluoroethanol. 54 references. (DLC)

Standardization of 123I and 18F for providing traceability of activity meters performed in the Radiopharmaceutical Production Service of the Instituto de Engenharia Nuclear, RJ, Brazil

International Nuclear Information System (INIS)

Andrade, E.A.L.; Delgado, J.U.; Iwahara, A.; Contic, C.C.

2013-01-01

The commercialization and use of radiopharmaceuticals in Brazil are regulated by Sanitary Vigilance National Agency which requiring Good Manufacturing Practices certification for all segments within the Nuclear Medicine. Quality Assurance Programmes should implement the standard requirements to ensure that radiopharmaceuticals have requirements quality to proving its efficiency. Several aspects should be controlled, and one of them is the traceability of the Radionuclides Activity Measurement in radiopharmaceuticals doses. This paper aims to provide traceability to dose calibrators (well type ionization chambers) used for 123 I and 18 F activity measurements in Radiopharmaceuticals Production Service placed in Institute of Nuclear Engineering, Rio de Janeiro, RJ, Brazil. (author)

{sup 18}F-Fluorodihydroxyphenylalanine vs other radiopharmaceuticals for imaging neuroendocrine tumours according to their type

Energy Technology Data Exchange (ETDEWEB)

Balogova, Sona [Comenius University and St. Elisabeth Institute, Department of Nuclear Medicine, Bratislava (Slovakia); Hopital Tenon, AP-HP and Universite Pierre et Marie Curie, Department of Nuclear Medicine, Paris (France); Talbot, Jean-Noel; Michaud, Laure; Huchet, Virginie; Kerrou, Khaldoun; Montravers, Francoise [Hopital Tenon, AP-HP and Universite Pierre et Marie Curie, Department of Nuclear Medicine, Paris (France); Nataf, Valerie [Hopital Tenon, AP-HP, Department of Radiopharmacy, Paris (France)

2013-06-15

6-Fluoro-({sup 18}F)-L-3,4-dihydroxyphenylalanine (FDOPA) is an amino acid analogue for positron emission tomography (PET) imaging which has been registered since 2006 in several European Union (EU) countries and by several pharmaceutical firms. Neuroendocrine tumour (NET) imaging is part of its registered indications. NET functional imaging is a very competitive niche, competitors of FDOPA being two well-established radiopharmaceuticals for scintigraphy, {sup 123}I-metaiodobenzylguanidine (MIBG) and {sup 111}In-pentetreotide, and even more radiopharmaceuticals for PET, including fluorodeoxyglucose (FDG) and somatostatin analogues. Nevertheless, there is no universal single photon emission computed tomography (SPECT) or PET tracer for NET imaging, at least for the moment. FDOPA, as the other PET tracers, is superior in diagnostic performance in a limited number of precise NET types which are currently medullary thyroid cancer, catecholamine-producing tumours with a low aggressiveness and well-differentiated carcinoid tumours of the midgut, and in cases of congenital hyperinsulinism. This article reports on diagnostic performance and impact on management of FDOPA according to the NET type, emphasising the results of comparative studies with other radiopharmaceuticals. By pooling the results of the published studies with a defined standard of truth, patient-based sensitivity to detect recurrent medullary thyroid cancer was 70 % [95 % confidence interval (CI) 62.1-77.6] for FDOPA vs 44 % (95 % CI 35-53.4) for FDG; patient-based sensitivity to detect phaeochromocytoma/paraganglioma was 94 % (95 % CI 91.4-97.1) for FDOPA vs 69 % (95 % CI 60.2-77.1) for {sup 123}I-MIBG; and patient-based sensitivity to detect midgut NET was 89 % (95 % CI 80.3-95.3) for FDOPA vs 80 % (95 % CI 69.2-88.4) for somatostatin receptor scintigraphy with a larger gap in lesion-based sensitivity (97 vs 49 %). Previously unpublished FDOPA results from our team are reported in some rare NET, such as

Sources of carrier F-19 in F-18 fluoride

Energy Technology Data Exchange (ETDEWEB)

Link, J. M.; Shoner, S. C.; Krohn, K. A. [University of Washington, Department of Radiology, Molecular Imaging Center, 1959 NE Pacific St., Box 356004, Seattle, WA 98195-6004 (United States)

2012-12-19

Fluorine-18 is used for many PET radiopharmaceuticals. Theoretically {sup 18}F should be carrier free and a good candidate for nanochemistry. However, {sup 18}F has 10 to 1000 times more stable fluorine atoms than radioactive atoms. In order to understand the source of carrier fluoride and other ions associated with {sup 18}F radiosynthesis, anion concentrations of different components of {sup 18}F target systems as well as solvents and chemicals used in radiosynthesis were measured. Results: The enriched water used for production of {sup 18}F had low levels of anions. In general, the sources of anions, particularly of fluoride, were the chemical reagents used for synthesis and trace contaminants in tubing, valves and fittings. A major component of contamination was nitrate from irradiation of dissolved nitrogen gas in the target water.

The optimization of 18F-nucleophilic fluorination reaction and its application in synthesis of VMAT2 imaging tracer: [18F]AV-133

International Nuclear Information System (INIS)

Liu Yajing; Zhu Lin; Karl, P.; Qu Wenchao

2010-01-01

Objective: The nucleophilic introduction of n.c.a. [ 18 F]F- into alkanes by nucleophilic reaction is the main method of preparing 18 F-labelled radiopharmaceuticals, and the efficient and rapid reaction is important in 18 F-labelled radiopharmaceuticals. Method: Using 2-(3-substitute propoxy)naphthalene as model compound, the optimal reaction condition was achieved by comparing the different [ 18 F]fluorination condition: 1)different leaving groups (-OTs, -I, -Br and -Cl), 2) different [ 18 F]fluorination catalysts (Kryptofix222/K 2 CO 3 and TBAHCO 3 ), 3) different reaction solvent (ACN, DMSO and DMF), 4) [ 18 F]fluorination temperature (40, 50 and 60 degree C) and 5) reaction time. The radiochemical yields were analyzed by TLC and HPLC. VMAT2 imaging tracer [ 18 F]AV-133 was synthesized under the optimal conditions. Results: From the experiment results, the reation activity was the highest when using -OTs as the leaving group, followed by -I and -Br, -Clunder the [ 18 F]fluorination condition of using K222/K 2 CO 3 as catalyst and ACN as solvent. And also, the radiochemical yield raised as the reaction time and temperature increased. The higher temperature, the shorter time to reach the equilibrium. When changing the solvent from ACN to DMSO, the radiochemical yields were increased. On the contrary, the radiochemical yields were decreasing by using DMF. Comparing the catalyst K222/K 2 CO 3 with TBAHCO 3 , the [ 18 F] fluorination of -OTs gave a higher radiochemical yield in the presence of K222/K 2 CO 3 . So the optimized [ 18 F]fluorination reaction condition was that choosing -OTs as the leaving group, the [ 18 F]fluorination reaction was efficient and gave higher radiochemical yield catalyzed by K222/K 2 CO 3 in DMSO at high temperature. [ 18 F]fluorination of AV-244 was found to provide the VMAT2 imaging tracer [ 18 F]AV-133 in 80 ± 2% radiochemical yield after reaction at 120 degree C for 3 min under optimized conditions. Conclusion: We have described an

Development and Successful Validation of Simple and Fast TLC Spot Tests for Determination of Kryptofix® 2.2.2 and Tetrabutylammonium in 18F-Labeled Radiopharmaceuticals

Directory of Open Access Journals (Sweden)

Matthias Kuntzsch

2014-05-01

Full Text Available Kryptofix® 2.2.2 (Kry or tetrabutylammonium (TBA are commonly used as phase transfer catalysts in 18F-radiopharmaceutical productions for positron emission tomography (PET. Due to their toxicity, quality control has to be performed before administration of the tracer to assure that limit concentration of residual reagent is not reached. Here, we describe the successful development and pharmaceutical validation (for specificity, accuracy and detection limit of a simplified color spot test on TLC plates. We were able to prove its applicability as a general, time and resources saving, easy to handle and reliable method in daily routine analyzing 18F-tracer formulations for Kry (in [18F]FDG or [18F]FECh or TBA contaminations (in [18F]FLT with special regard to complex matrix compositions.

Radiosynthesis of [{sup 18}F]fluoromethyldeoxyspergualin for molecular imaging of heat shock proteins

Energy Technology Data Exchange (ETDEWEB)

Ghosh, Pradip; Li, King C. [Department of Radiology, Nuclear Medicine Division, Methodist Hospital Research Institute, Weill Cornell Medical College, 6565 Fannin Street, MB1-066, Houston, TX 77030 (United States); Lee, Daniel Y., E-mail: dlee@tmhs.or [Department of Radiology, Nuclear Medicine Division, Methodist Hospital Research Institute, Weill Cornell Medical College, 6565 Fannin Street, MB1-066, Houston, TX 77030 (United States)

2011-03-15

To probe the in vivo role of stress response factors in normal physiology and in solid tumors we have designed a stable {sup 18}F-labeled molecular imaging agent based on a ligand for heat shock protein 70 (HSP70). We describe the synthesis of [{sup 18}F] fluorodeoxymethylspergualin ([{sup 18}F]MeDSG) as a new radiopharmaceutical probe using a prosthetic group, [{sup 18}F]SFB, for efficient and rapid radiolabeling. Ongoing molecular imaging studies are under way to detect HSP70 expression in tumors by positron emission tomography.

Synthesis, quality control and dosimetry of the radiopharmaceutical 18F-sodium fluoride produced at the Center for Development of Nuclear Technology - CDTN

Energy Technology Data Exchange (ETDEWEB)

Silveira, Marina Bicalho; Soares, Marcella Araugio; Valente, Eduardo Sarmento; Waquil, Samira Soares; Santos, Raquel Gouvea dos; Silva, Juliana Batista da, E-mail: silvajb@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Serv. de Aplicacao das Radiacoes na Saude; Ferreira, Andrea Vidal [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Serv. de Reator e Irradiacoes

2010-07-15

{sup 18}F-Sodium fluoride (Na{sup 18}F) is a radiopharmaceutical used for diagnosis in nuclear medicine by positron emission tomography (PET) imaging. Bone scintigraphy is normally performed using {sup 99m}Tc- MDP. However, {sup 18}F PET scans promise high quality imaging with increased resolution and improved sensitivity and specificity. In order to make available a tool for more specific studies of tumors and non oncological diseases of bone tissue, the UPPR/CDTN team undertook the production and quality control of Na{sup 18}F injectable solution with the physical-chemical, microbiological and biological characteristics recommended in the U.S. Pharmacopeia. Na{sup 18}F radiochemical purity was 96.7 {+-} 1.3 %, with Rf= 0.026 {+-} 0.006. The product presented a pH of 5.3 {+-} 0.6, half life of 109.0 {+-} 0.8 minutes, endotoxin limit < 5.0 EU.mL{sup -1} and no microbial contaminants. The biodistribution of Na{sup 18}F was similar to that described in the literature, with a clearance of 0.19 mL.min{sup -1} and distribution volume of 18.76 mL. The highest bone concentration (5.0 {+-} 0.5 %ID.g{sup -1}) was observed 20 minutes after injection. Na{sup 18}F produced at the UPPR presented all the quality assurance requirements of the U.S. Pharmacopeia and can be safely used for clinical bone imaging. (author)

Click synthesis of PET radiopharmaceuticals

International Nuclear Information System (INIS)

Xu Mei; Kuang Chunxiang

2009-01-01

Increasing attention has been focused on synthesis radiopharmaceuticals for positron emission tomography (PET). The recent years witnessed applications of click chemistry to PET radiopharmaceutical synthesis,because of its distinctive advantages including high speed,yield and stereospecificity under mild conditions. Synthesis of 18 F-labeled and 11 C-labeled radiopharmaceuticals and intermediates via click chemistry are reviewed. The future trend of click chemistry for the synthesis of PET radiopharmaceutical is prospected. (authors)

Performance evaluation of activimeter for PET radiopharmaceutical measuring based on 18F

International Nuclear Information System (INIS)

Fragoso, Maria da Conceicao de Farias; Oliveira, Mercia Liane de; Lima, Fernando Roberto de Andrade

2014-01-01

Proficiency test is an essential tool to assess the reliability and accuracy of measurements. In this work, proficiency tests (Z-score, accuracy and relative deviation) were applied to evaluate the performance of the activimeter used at Radiopharmaceuticals Production Division of the Regional Center for Nuclear Sciences of the Northeast (CRCN-NE/CNEN). The results were evaluated in compliance with ISO/IEC Guide 43-1. Additionally, correction factors for different measurement geometries were determined experimentally for those devices. (author)

Radiolysis of 2-[{sup 18}F]fluoro-2-deoxy-D-glucose ([{sup 18}F]FDG) and the role of ethanol and radioactive concentration

Energy Technology Data Exchange (ETDEWEB)

Jacobson, Mark S. [Division of Nuclear Medicine, Mayo Clinic, Rochester, MN (United States)], E-mail: jacobson.mark17@mayo.edu; Dankwart, Heather R. [Division of Nuclear Medicine, Mayo Clinic, Rochester, MN (United States); Mahoney, Douglas W. [Division of Biostatistics, Mayo Clinic, Rochester, MN (United States)

2009-06-15

Radiolysis is the process by which radioactively labeled compounds degrade. Many positron emission tomography (PET) radiopharmaceuticals produced with high radioactive concentrations and specific activities exhibit low radiochemical purity because of radiolysis. Little data exist that describe the radiolytic decomposition of 2-[{sup 18}F]fluoro-2-deoxy-D-glucose ([{sup 18}F]FDG). The objective of our study was to profile the degradation of [{sup 18}F]FDG at various radioactive concentrations by measuring radiochemical purity at different time intervals and to study the effects of ethanol, a well-known reductant stabilizer of [{sup 18}F]FDG preparations.

Feasibility and dosimetry studies for 18F-NOS as a potential PET radiopharmaceutical for inducible nitric oxide synthase in humans.

Science.gov (United States)

Herrero, Pilar; Laforest, Richard; Shoghi, Kooresh; Zhou, Dong; Ewald, Gregory; Pfeifer, John; Duncavage, Eric; Krupp, Kitty; Mach, Robert; Gropler, Robert

2012-06-01

Nitric oxide (NO), the end product of the inducible form of NO synthase (iNOS), is an important mediator of a variety of inflammatory diseases. Therefore, a radiolabeled iNOS radiopharmaceutical for assessing iNOS protein concentration as a marker for its activity would be of value to the study and treatment of NO-related diseases. We recently synthesized an (18)F-radiolabeled analog of the reversible NOS inhibitor, 2-amino-4-methylpyridine ((18)F-NOS), and confirmed its utility in a murine model of lung inflammation. To determine its potential for use in humans, we measured (18)F-NOS myocardial activity in patients after orthotopic heart transplantation (OHT) and correlated it with pathologic allograft rejection, tissue iNOS levels, and calculated human radiation dosimetry. Two groups were studied-a kinetic analysis group and a dosimetry group. In the kinetic analysis group, 10 OHT patients underwent dynamic myocardial (18)F-NOS PET/CT, followed by endomyocardial biopsy. Myocardial (18)F-NOS PET was assessed using volume of distribution; standardized uptake values at 10 min; area under the myocardial moment curve (AUMC); and mean resident time at 5, 10, and 30 min after tracer injection. Tissue iNOS levels were measured by immunohistochemistry. In the dosimetry group, the biodistribution and radiation dosimetry were calculated using whole-body PET/CT in 4 healthy volunteers and 12 OHT patients. The combined time-activity curves were used for residence time calculation, and organ doses were calculated with OLINDA. Both AUMC at 10 min (P measurements with acceptable radiation exposure. Although further modifications to improve the performance of (18)F-NOS are needed, these data show the feasibility of PET of iNOS in the heart and other tissues.

Development of [18F]halofluorination and [18F]fluoride ion displacement reactions for the synthesis of F-18 labelled radiopharmaceuticals

International Nuclear Information System (INIS)

Chi, D.Y.

1986-01-01

Two fluorine-18 labeling methods, [ 18 F]halofluorination and [ 18 F]fluoride ion displacement reactions, have been developed to assess their potential for labeling molecules with the positron-emitting radionuclide fluorine-18 at the no-carrier-added level. Olefin halofluorination involves the in situ generation of a halogen-fluoride reagent and subsequent addition to an olefin. The characteristics of this reaction were investigated with three model olefins (allylbenzene, 1-hexene, and propene). A two-step method for the preparation of fluoroalkyl substituted amines and amides has been achieved. The sequence involves fluoride ion displacement of trifluoromethanesulfonates (triflates) from short-chain haloalkyl triflates, followed by fluoroalkylation of the amine or amide. Alternatively, short-chain fluoroalkyl halides can be prepared by halofluorination of a terminal olefin. These reactions have been used to prepare various fluoroalkyl derivatives of 1-phenylpiperazine and N-fluoroalkyl derivatives of the neuroleptic agent spiperone. A series of fluorine-18 labeled N-fluoroalkylated spiperone derivatives were synthesized by N-alkylation of spiperone with fluoroalkyl halides

Radiopharmaceuticals for neurotransmitter imaging

Energy Technology Data Exchange (ETDEWEB)

Oh, Seung Jun [Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

2007-04-15

Neurotransmitter imaging with radiopharmaceuticals plays major role for understanding of neurological and psychiatric disorders such as Parkinson's disease and depression. Radiopharmaceuticals for neurotransmitter imaging can be divided to dopamine transporter imaging radiopharmaceuticals and serotonin transporter imaging radiopharmaceuticals. Many kinds of new dopamine transporter imaging radiopharmaceuticals has a tropane ring and they showed different biological properties according to the substituted functional group on tropane ring. After the first clinical trials with [{sup 123}I] {beta} -CIT, alkyl chain substituent introduced to tropane ring amine to decrease time for imaging acquisition and to increase selectivity. From these results, [{sup 123}I]PE2I, [18F]FE-CNT, [{sup 123}I]FP-CIT and [{sup 18}F]FP-CIT were developed and they showed high uptake on the dopamine transporter rich regions and fast peak uptake equilibrium time within 4 hours after injection. [{sup 11}C]McN 5652 was developed for serotonin transporter imaging but this compound showed slow kinetics and high background radioactivity. To overcome these problems, new diarylsulfide backbone derivatives such as ADAM, ODAM, AFM, and DASB were developed. In these candidates, [{sup 11}C]AFM and [{sup 11}C]DASB showed high binding affinity to serotonin transporter and fast in vivo kinetics. This paper gives an overview of current status on dopamine and serotonin transporter imaging radiopharmaceuticals and the development of new lead compounds as potential radiopharmaceuticals by medicinal chemistry.

Acute and subacute toxicity of 18F-FDG

International Nuclear Information System (INIS)

Dantas, Danielle M.; Silva, Natanael G. da; Manetta, Ana Paula; Osso Junior, Joao A.

2013-01-01

Before initiating clinical trials of a new drug, it is necessary to perform a battery of safety tests, for evaluating the risk in humans. Radiopharmaceuticals must be tested taking into account its specificity, duration of treatment and especially the toxicity of both, the unlabelled molecule and its radionuclide, apart from impurities emanating from radiolysis. In Brazil the production of radiopharmaceuticals was not regulated until the end of 2009, when ANVISA established the Resolutions No. 63, which refers to the Good Manufacturing Practices of radiopharmaceuticals and No. 64 which seeks the registration of radiopharmaceuticals. Nowadays IPEN produces one of the most important radiopharmaceutical for nuclear medicine, the 18 F-FDG, which is used in the diagnosis. The objective of this study is to assess systemic toxicity (acute / subacute) of 18 F-FDG in an in vivo test system, as recommended by the RDC No. 64. In acute tests the administration occurred on the first day, healthy rats were observed for 14 days reporting their clinical signs and water consumption, and on the 15th day they were euthanized and necropsied. The assay of subacute toxicity observations were made over a period of 28 days and the first dose was administered at the beginning of the test and after a fortnight a second dose was administered. The parameters evaluated were the necropsy, histopathology of target organs, hematology studies and liver and kidney function. The results are being processed and evaluated. Initial observations did not show any acute toxicity in animals when compared to control animals. (author)

Chilean experience in production of 18F-FDG from 18F in a reactor

International Nuclear Information System (INIS)

Chandia, M.; Godoy, N.; Errazu, X.; Hernandez; Figols, M.; Firnau, G.; Tronsoco, F.

2000-01-01

18 F-FDG (fluorine-deoxy-D-glucose) is an important and useful radiopharmaceutical for imaging and study of myocardial viability. Usually cyclotron-produced 18 F is used to label 18 F-FDG. The availability of a 5 MW Nuclear Reactor in Chile and the absence of a quality cyclotron to produce 18 F required that we developed a method in order to obtain suitable 18 F to label 18 F-FDG using the facilities we have at the Nuclear Center of La Reina, Chilean Nuclear Energy Commission. The nuclear reactions involved are: 6 Li(n,aα) 3 H and 16 O( 3 H,n) 18 F. Enriched Li 2 CO 3 ( 6 Li = 95 %) was irradiated in a 5 MW swimming pool type nuclear reactor with a neutron flux of 5. 7 x 10 13 n cm -2 s -1 for 4 hours. The irradiated Li 2 CO 3 was dissolved in H 2 SO 4 (1:1) and distilled as trimethylsilyl( 18 F)fluoride ( 18 F-TMS). The labelling of the sugar was carried out using the method described by Hamacker. The 18 F-TMS was trapped in a solution of acetonitrile, water, potassium carbonate, and kriptofix and hydrolysed to form 18 F fluoride. The nucleophilic complex reacts with 1,3,4,6, tetra-O-acetyl- 2-O-trifluoromethanesulfonyl-bβ-D-mannopyranose. The acetylated carbohydrate by acid hydrolysis produces 18 F-FDG. The final product was purified using an ion retarding resin (AG11-A8) and a system two Sep Pak Plus: Alumina and C-18 cartridge and sterilised by Millipore 0.22 μm filter. The 18 F-FDG was obtained in an apyrogenic and sterile solution. The 18 F radionuclide purity was higher than 99.9% and the radiochemical purity ofthe 18 F-FDG obtained was over than 99%. Residual 3 H content was as low as 20 (Bq 3 H/MBq 18 F-FDG.). The yield of the process 18 F-FDG was 13.2 %. (authors)

Sulfonyl fluoride-based prosthetic compounds as potential 18F labelling agents.

Science.gov (United States)

Inkster, James A H; Liu, Kate; Ait-Mohand, Samia; Schaffer, Paul; Guérin, Brigitte; Ruth, Thomas J; Storr, Tim

2012-08-27

Nucleophilic incorporation of [(18)F]F(-) under aqueous conditions holds several advantages in radiopharmaceutical development, especially with the advent of complex biological pharmacophores. Sulfonyl fluorides can be prepared in water at room temperature, yet they have not been assayed as a potential means to (18)F-labelled biomarkers for PET chemistry. We developed a general route to prepare bifunctional 4-formyl-, 3-formyl-, 4-maleimido- and 4-oxylalkynl-arylsulfonyl [(18)F]fluorides from their sulfonyl chloride analogues in 1:1 mixtures of acetonitrile, THF, or tBuOH and Cs[(18)F]F/Cs(2)CO(3(aq.)) in a reaction time of 15 min at room temperature. With the exception of 4-N-maleimide-benzenesulfonyl fluoride (3), pyridine could be used to simplify radiotracer purification by selectively degrading the precursor without significantly affecting observed yields. The addition of pyridine at the start of [(18)F]fluorination (1:1:0.8 tBuOH/Cs(2)CO(3(aq.))/pyridine) did not negatively affect yields of 3-formyl-2,4,6-trimethylbenzenesulfonyl [(18)F]fluoride (2) and dramatically improved the yields of 4-(prop-2-ynyloxy)benzenesulfonyl [(18)F]fluoride (4). The N-arylsulfonyl-4-dimethylaminopyridinium derivative of 4 (14) can be prepared and incorporates (18)F efficiently in solutions of 100 % aqueous Cs(2)CO(3) (10 mg mL(-1)). As proof-of-principle, [(18)F]2 was synthesised in a preparative fashion [88(±8) % decay corrected (n=6) from start-of-synthesis] and used to radioactively label an oxyamino-modified bombesin(6-14) analogue [35(±6) % decay corrected (n=4) from start-of-synthesis]. Total preparation time was 105-109 min from start-of-synthesis. Although the (18)F-peptide exhibited evidence of proteolytic defluorination and modification, our study is the first step in developing an aqueous, room temperature (18)F labelling strategy. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Robotic production of 2-deoxy-2-[18F]fluoro-D-glucose: a routine method of synthesis using tetrabutylammonium [18F]fluoride

International Nuclear Information System (INIS)

Brodack, J.W.; Dence, C.S.; Kilbourn, M.R.; Welch, M.J.

1988-01-01

Using existing robotic hardware and software programs developed for the synthesis of several positron-emitting radiopharmaceuticals for PET imaging, the additional automated synthesis of 2-deoxy-2-[ 18 F]fluoro-D-glucose (2-[ 18 F]FDG) has been incorporated into our Zymate Laboratory Automation System. The robotic synthesis of 2-[ 18 F]FDG took less than one week to implement, including the organization of software subroutines and construction of an additional heating station. The end of synthesis yield (12-17%) and radiochemical purity (96-99%) for the robotic preparation of 2-[ 18 F]FDG is similar to that of the manual synthesis. This automated method uses anhydrous tetrabutylammonium [ 18 F]fluoride as the reactive fluoride source in the labeling step. The procedure is a modification of the synthesis reported by Hamacher et al. [Hamacher et al. (1986) J. Nucl. Med. 27, 235]. (author)

Pilot Preclinical and Clinical Evaluation of (4S-4-(3-[18F]Fluoropropyl-L-Glutamate (18F-FSPG for PET/CT Imaging of Intracranial Malignancies.

Directory of Open Access Journals (Sweden)

Erik S Mittra

Full Text Available (S-4-(3-[18F]Fluoropropyl-L-glutamic acid (18F-FSPG is a novel radiopharmaceutical for Positron Emission Tomography (PET imaging. It is a glutamate analogue that can be used to measure xC- transporter activity. This study was performed to assess the feasibility of 18F-FSPG for imaging orthotopic brain tumors in small animals and the translation of this approach in human subjects with intracranial malignancies.For the small animal study, GS9L glioblastoma cells were implanted into brains of Fischer rats and studied with 18F-FSPG, the 18F-labeled glucose derivative 18F-FDG and with the 18F-labeled amino acid derivative 18F-FET. For the human study, five subjects with either primary or metastatic brain cancer were recruited (mean age 50.4 years. After injection of 300 MBq of 18F-FSPG, 3 whole-body PET/Computed Tomography (CT scans were obtained and safety parameters were measured. The three subjects with brain metastases also had an 18F-FDG PET/CT scan. Quantitative and qualitative comparison of the scans was performed to assess kinetics, biodistribution, and relative efficacy of the tracers.In the small animals, the orthotopic brain tumors were visualized well with 18F-FSPG. The high tumor uptake of 18F-FSPG in the GS9L model and the absence of background signal led to good tumor visualization with high contrast (tumor/brain ratio: 32.7. 18F-FDG and 18F-FET showed T/B ratios of 1.7 and 2.8, respectively. In the human pilot study, 18F-FSPG was well tolerated and there was similar distribution in all patients. All malignant lesions were positive with 18F-FSPG except for one low-grade primary brain tumor. In the 18F-FSPG-PET-positive tumors a similar T/B ratio was observed as in the animal model.18F-FSPG is a novel PET radiopharmaceutical that demonstrates good uptake in both small animal and human studies of intracranial malignancies. Future studies on larger numbers of subjects and a wider array of brain tumors are planned.ClinicalTrials.gov NCT

Acute and subacute toxicity of {sup 18F}-FDG

Energy Technology Data Exchange (ETDEWEB)

Dantas, Danielle M.; Silva, Natanael G. da; Manetta, Ana Paula; Osso Junior, Joao A., E-mail: danielle_2705@hotmail.com, E-mail: jaossoj@yahoo.com.br, E-mail: ngsilva@ipen.br, E-mail: apaulasp2008@hotmail.co [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

2013-07-01

Before initiating clinical trials of a new drug, it is necessary to perform a battery of safety tests, for evaluating the risk in humans. Radiopharmaceuticals must be tested taking into account its specificity, duration of treatment and especially the toxicity of both, the unlabelled molecule and its radionuclide, apart from impurities emanating from radiolysis. In Brazil the production of radiopharmaceuticals was not regulated until the end of 2009, when ANVISA established the Resolutions No. 63, which refers to the Good Manufacturing Practices of radiopharmaceuticals and No. 64 which seeks the registration of radiopharmaceuticals. Nowadays IPEN produces one of the most important radiopharmaceutical for nuclear medicine, the {sup 18}F-FDG, which is used in the diagnosis. The objective of this study is to assess systemic toxicity (acute / subacute) of {sup 18}F-FDG in an in vivo test system, as recommended by the RDC No. 64. In acute tests the administration occurred on the first day, healthy rats were observed for 14 days reporting their clinical signs and water consumption, and on the 15th day they were euthanized and necropsied. The assay of subacute toxicity observations were made over a period of 28 days and the first dose was administered at the beginning of the test and after a fortnight a second dose was administered. The parameters evaluated were the necropsy, histopathology of target organs, hematology studies and liver and kidney function. The results are being processed and evaluated. Initial observations did not show any acute toxicity in animals when compared to control animals. (author)

Synthesis and quality control of [18F] fluorothymidine

International Nuclear Information System (INIS)

Nascimento, Leonardo Tafas C.; Silva, Juliana B.; Silveira, Marina B.; Santos, Priscilla F.; Faria, Tiago

2013-01-01

The Positron Emission Tomography (PET) is a technique that allows early diagnosis of various diseases by detecting metabolic changes of cells, in addition to being a noninvasive technique. The most widely used radiopharmaceutical for PET imaging is [ 18 F] Fludesoxiglucose ( 18 FDG), which is a marker of glucose metabolism and has high sensitivity and specificity for diagnosis and staging of various cancers. However, some carcinomas do not have high glucose consumption, besides 18 FDG possess high urinary excretion rate interfering with the detection of tumors in pelvis and high uptake in brain and in inflammation, reducing the contrast tumor / background. The radiotracer 3'-fluoro-L-3'-deoxythymidine ( 18 FLT) is an analogue of thymidine used as an alternative to 18 FDG for detecting tumors with high proliferation rate. The aim of this work was to develop [ 18 F] Fluorothymidine synthesis and quality control at the Radiopharmaceuticals Research and Production Facility of CDTN/CNEN. The synthesis was adapted from that used to 18 FDG, based on the methodologies described in related papers. Radiochemical purity and impurities levels were determined by HPLC, RTLC and GC techniques. Total synthesis time was 35 minutes and the radiochemical yield in the end of bombardment (EOB) was 7%, with a radiochemical purity of about 93%. Radionuclidic identity and purity, pH, residual solvents, radiochemical and chemical purity were evaluated according to analytical methods described on the literature and on the United States Pharmacopeia (USP 32). Residual levels of Stavudine, Thymine and Thymidine were found and are under toxicological investigation in order to establish a maximum amount allowed in the final product. (author)

SU-E-I-82: PET Radiopharmaceuticals for Prostate Cancer Imaging: A Review

International Nuclear Information System (INIS)

Fernandes, F; Silva, D da; Rodrigues, L

2015-01-01

Purpose: The aim of this work was to review new and clinical practice PET radiopharmaceuticals for prostate cancer imaging. Methods: PET radiopharmaceuticals were reviewed on the main databases. Availability, dosimetry, accuracy and limitations were considered. Results: The following radioisotopes with respective physical half-life and mean positron energy were found: 18 F (109,7 min, 249,8 keV), 89 Zr (78,4 hs, 395,5 keV), 11 C (20,4 min, 385,7 keV) and 68 Ga (67,8 min, 836 keV). 68 Ga was the only one not produced by cyclotron. Radiopharmaceuticals uptake by glucose metabolism ( 18 F-FDG), lipogenesis ( 11 C-Choline and 11 C-Acetate), amino acid transport (Anti- 18 F-FACBC), bone matrix ( 18 F-NaF), prostatespecific membrane antigen ( 68 Ga-PSMA and 89 Zr-J591), CXCR receptors ( 89 Ga-Pentixafor), adrenal receptors ( 18 F-FDHT) and gastrin release peptide receptor (bombesin analogue). Most of radiopharmaceuticals are urinary excretion, so bladder is the critical organ. 11C-choline (pancreas), Anti- 18 FFACBC (liver) and 18 F-FBDC (stomach wall) are the exception. Higher effective dose was seen 18 F-NaF (27 μSv/MBq) while the lowest was 11 CAcetate (3,5 μSv/MBq). Conclusion: Even though 18 F-FDG has a large availability its high urinary excretion and poor uptake to slow growing disease offers weak results for prostate cancer. Better accuracy is obtained when 18 F-NaF is used for bone metastatic investigation although physicians tend to choose bone scintigraphy probably due to its cost and practice. Many guidelines in oncology consider 11 C or 18 F labeled with Choline the gold standard for biochemical relapse after radical treatment. Local, lymph node and distant metastatic relapse can be evaluated at same time with this radiopharmaceutical. There is no consensus over bigger urinary excretion for 18 F labeling. Anti- 18 F-FACBC, 68 Ga-PSMA and 68 Ga-Pentixafor are demonstrating good results but more researches are needed. While PSMA imaging seems to be

Fast and repetitive in-capillary production of [{sup 18}F]FDG

Energy Technology Data Exchange (ETDEWEB)

Wester, Hans-Juergen; Schoultz, Bent Wilhelm; Hultsch, Christina; Henriksen, Gjermund [Technische Universitaet Muenchen, Department of Nuclear Medicine, Klinikum rechts der Isar, Munich (Germany)

2009-04-15

The increasing demand for radiopharmaceuticals to be provided reproducibly and flexibly with high frequency for clinical application and animal imaging would be better met by improved or even new strategies for automated tracer production. Radiosynthesis in microfluidic systems, i.e. narrow tubing with a diameter of approximately 50-500 {mu}m, holds promise for providing the means for repetitive multidose and multitracer production. In this study, the performance of a conceptually simple microfluidic device integrated into a fully automated synthesis procedure for in-capillary radiosynthesis (ICR) of clinical grade [{sup 18}F]FDG was evaluated. The instrumental set-up consisted of pumps for reagent and solvent delivery into small mixing chambers, {mu}-fluidic capillaries, in-process radioactivity monitoring, solid-phase extraction and on-column deprotection of the {sup 18}F-labelled intermediate followed by on-line formulation of [{sup 18}F]FDG. In-capillary{sup 18}F-fluorination of 2.1 {mu}mol 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulphonyl-beta-d-mannopyranose (TATM; precursor for [{sup 18}F]FDG) in acetonitrile (MeCN) at a flow rate of 0.3 ml/min within 40 s and subsequent on-line hydrolysis of the intermediate by treatment with 0.3 M NaOH for 1 min at 40 C resulted in a radiochemical yield of 88 {+-} 4% within <7 min. Reproducibility, robustness and suitability as a fast and efficient radiopharmaceutical research tool for {sup 18}F-fluorination was demonstrated by eight independent, sequentially performed ICRs which provided identical tracer quality (radiochemical purity >97%, MeCN <5 {mu}g/ml) and similar absolute yields (approximately 1.4 GBq). The described ICR process is a simple and efficient alternative to classic radiotracer production systems and provides a comparatively cheap instrumental methodology for the repetitive production of [{sup 18}F]FDG with remarkably high efficiency and high yield under fully automated conditions. Although the results

Initial results of hypoxia imaging using 1-α-d-(5-deoxy-5-[18F]-fluoroarabinofuranosyl)-2-nitroimidazole (18F-FAZA)

International Nuclear Information System (INIS)

Postema, Ernst J.; McEwan, Alexander J.B.; Riauka, Terence A.; Kumar, Piyush; Richmond, Dacia A.; Abrams, Douglas N.; Wiebe, Leonard I.

2009-01-01

Tumour hypoxia is thought to play a significant role in the outcome of solid tumour therapy. Positron emission tomography (PET) is the best-validated noninvasive technique able to demonstrate the presence of hypoxia in vivo. The locally developed PET tracer for imaging hypoxia, 1-α-d-(5-deoxy-5-[ 18 F]-fluoroarabinofuranosyl)-2-nitroimidazole ( 18 F-FAZA), has been shown to accumulate in experimental models of tumour hypoxia and to clear rapidly from the circulation and nonhypoxic tissues. The safety and general biodistribution patterns of this radiopharmaceutical in patients with squamous cell carcinoma of the head and neck (HNSCC), small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC), malignant lymphoma, and high-grade gliomas, were demonstrated in this study. Patients with known primary or suspected metastatic HNSCC, SCLC or NSCLC, malignant lymphoma or high-grade gliomas were dosed with 5.2 MBq/kg of 18 F-FAZA, then scanned 2-3 h after injection using a PET or PET/CT scanner. Images were interpreted by three experienced nuclear medicine physicians. The location and relative uptake scores (graded 0 to 4) of normal and abnormal 18 F-FAZA biodistribution patterns, the calculated tumour-to-background (T/B) ratio, and the maximum standardized uptake value were recorded. Included in the study were 50 patients (32 men, 18 women). All seven patients with high-grade gliomas showed very high uptake of 18 F-FAZA in the primary tumour. In six out of nine patients with HNSCC, clear uptake of 18 F-FAZA was observed in the primary tumour and/or the lymph nodes in the neck. Of the 21 lymphoma patients (15 with non-Hodgkin's lymphoma and 6 with Hodgkin's disease), 3 demonstrated moderate lymphoma-related uptake. Of the 13 lung cancer patients (12 NSCLC, 1 SCLC), 7 had increased 18 F-FAZA uptake in the primary lung tumour. No side effects of the administration of 18 F-FAZA were observed. This study suggests that 18 F-FAZA may be a very useful radiopharmaceutical

SU-E-I-82: PET Radiopharmaceuticals for Prostate Cancer Imaging: A Review

Energy Technology Data Exchange (ETDEWEB)

Fernandes, F [Delfin Farmacos e Derivados Ltda, Lauro De Freitas, Bahia (Brazil); Escola Bahiana de Medicina e Saude Publica, Salvador, Bahia (Brazil); Silva, D da [Delfin Farmacos e Derivados Ltda, Lauro De Freitas, Bahia (Brazil); Rodrigues, L [Escola Bahiana de Medicina e Saude Publica, Salvador, Bahia (Brazil)

2015-06-15

Purpose: The aim of this work was to review new and clinical practice PET radiopharmaceuticals for prostate cancer imaging. Methods: PET radiopharmaceuticals were reviewed on the main databases. Availability, dosimetry, accuracy and limitations were considered. Results: The following radioisotopes with respective physical half-life and mean positron energy were found: {sup 18}F (109,7 min, 249,8 keV), {sup 89}Zr (78,4 hs, 395,5 keV), {sup 11}C (20,4 min, 385,7 keV) and {sup 68}Ga (67,8 min, 836 keV). {sup 68}Ga was the only one not produced by cyclotron. Radiopharmaceuticals uptake by glucose metabolism ({sup 18}F-FDG), lipogenesis ({sup 11}C-Choline and {sup 11}C-Acetate), amino acid transport (Anti-{sup 18}F-FACBC), bone matrix ({sup 18}F-NaF), prostatespecific membrane antigen ({sup 68}Ga-PSMA and {sup 89}Zr-J591), CXCR receptors ({sup 89}Ga-Pentixafor), adrenal receptors ({sup 18}F-FDHT) and gastrin release peptide receptor (bombesin analogue). Most of radiopharmaceuticals are urinary excretion, so bladder is the critical organ. 11C-choline (pancreas), Anti-{sup 18}FFACBC (liver) and {sup 18}F-FBDC (stomach wall) are the exception. Higher effective dose was seen {sup 18}F-NaF (27 μSv/MBq) while the lowest was {sup 11}CAcetate (3,5 μSv/MBq). Conclusion: Even though {sup 18}F-FDG has a large availability its high urinary excretion and poor uptake to slow growing disease offers weak results for prostate cancer. Better accuracy is obtained when {sup 18}F-NaF is used for bone metastatic investigation although physicians tend to choose bone scintigraphy probably due to its cost and practice. Many guidelines in oncology consider {sup 11}C or {sup 18}F labeled with Choline the gold standard for biochemical relapse after radical treatment. Local, lymph node and distant metastatic relapse can be evaluated at same time with this radiopharmaceutical. There is no consensus over bigger urinary excretion for {sup 18}F labeling. Anti-{sup 18}F-FACBC, {sup 68}Ga-PSMA and {sup

Effect of the dilution factor on 18FDG and Na18F samples for bacterial endotoxin test using PTS (portable test system)

International Nuclear Information System (INIS)

Silveira, Marina B.; Costa, Flavia M.; Ferreira, Soraya Z.

2011-01-01

18 FDG and Na 18 F are radiopharmaceuticals produced as sterile solutions suitable for intravenous administration, which must contain no more than 175 EV/V. The most commonly used approach to detect endotoxins is the gelclot technique that requires 60 minutes for results. For radiopharmaceuticals containing short-life radionuclides, such as 18 F, there is an increasing interest for faster quality control methods. FDA licensed the Endosafe, PTS, a kinetic chromogenic endotoxin detection system that takes about 15 minutes for results. As other techniques, PTS test is susceptible to interferences which can be solved by product dilution. The aim of this study was to establish the best dilution of 18 FDG and Na 18 F for PTS analysis. Two different dilution factors for 18 FDG and 1:10 for Na 18 F were essayed: 1:10 and 1:100. 18 FDG and Na 18 solutions were prepared by the addition of LAL reagent water. Considering the assay acceptance criteria, the best dilution factor was 1:100 for 18 FDG and 1:10 for Na 18 F. The recovery of the product positive control was 98-12% for 18 FDG 1:100 and 104-120% for Na 18 F 1:10, which were, in both cases, within the specification (50-200%) and very close to 100%. Results obtained with these dilution studies were important to establish the most appropriate and non-interfering dilution factor for 18 FDG and Na 18 F routine endotoxin test. (author)

Synthesis and quality control of [{sup 18}F] fluorothymidine

Energy Technology Data Exchange (ETDEWEB)

Nascimento, Leonardo Tafas C.; Silva, Juliana B.; Silveira, Marina B.; Santos, Priscilla F.; Faria, Tiago, E-mail: ltcn@cdtn.br [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

2013-07-01

The Positron Emission Tomography (PET) is a technique that allows early diagnosis of various diseases by detecting metabolic changes of cells, in addition to being a noninvasive technique. The most widely used radiopharmaceutical for PET imaging is [{sup 18}F] Fludesoxiglucose ({sup 18}FDG), which is a marker of glucose metabolism and has high sensitivity and specificity for diagnosis and staging of various cancers. However, some carcinomas do not have high glucose consumption, besides {sup 18}FDG possess high urinary excretion rate interfering with the detection of tumors in pelvis and high uptake in brain and in inflammation, reducing the contrast tumor / background. The radiotracer 3'-fluoro-L-3'-deoxythymidine ({sup 18}FLT) is an analogue of thymidine used as an alternative to {sup 18}FDG for detecting tumors with high proliferation rate. The aim of this work was to develop [{sup 18}F] Fluorothymidine synthesis and quality control at the Radiopharmaceuticals Research and Production Facility of CDTN/CNEN. The synthesis was adapted from that used to {sup 18}FDG, based on the methodologies described in related papers. Radiochemical purity and impurities levels were determined by HPLC, RTLC and GC techniques. Total synthesis time was 35 minutes and the radiochemical yield in the end of bombardment (EOB) was 7%, with a radiochemical purity of about 93%. Radionuclidic identity and purity, pH, residual solvents, radiochemical and chemical purity were evaluated according to analytical methods described on the literature and on the United States Pharmacopeia (USP 32). Residual levels of Stavudine, Thymine and Thymidine were found and are under toxicological investigation in order to establish a maximum amount allowed in the final product. (author)

Comparison of [18F]FLT and [18F]FDG in in vitro cancer cell uptake and glucose effect

International Nuclear Information System (INIS)

Soo Jung Lim; Jin-Sook Ryu; Heuiran Lee; Seok Young Kim; Seung Jun Oh; Dae Hyuk Moon

2004-01-01

[18F]FLT is a new radiopharmaceutical for cell proliferation. We compared [18F]FLT and [18F]FDG in in vitro cancer cell uptake and glucose effect. Method: In vitro cancer cell uptake of [18F]FLT was evaluated using SCC7(mouse squamous cell carcinoma). At 24 hours after seeding 1 x 106 cells/well in 6 well plates with RPMI 1640 medium, culture media were changed to medium with glucose free or glucose concentration of 100 mg/dl. Then, [18F]FLT 5 μCi/50 ml was added to each well. After incubation for 30, 60, 90, 120 minutes, cells were washed twice by PBS, and harvested using 0.25% trypsin-EDTA. After centrifugation and counting at gamma counter, cell uptake was calculated by % activity of cellular uptake to total activity of cell and supernatant. For comparison, same tumor cell uptake experiment was performed with [18F]FDG. Results: After incubation with SCC7 cell line for 30, 60, 90, 120 minutes, [18F]FLT showed 1.95%, 2.17%, 2.10% and 2.80% of cell uptake in glucose free media, respectively. The results [18F]FLT uptake in glucose 100 mg/dl media were 1.82%, 1.87%, 1.97%, and 2.94%, respectively. The results of [18F]FDG in glucose free media were 2.50%, 3.47%, 5.04%, and 10.4%, whereas those in glucose 100 mg/dl media were 1.60%, 1.79%, 1.53%, and 1.82%, respectively. Conclusion: In contrast to [18F]FDG, [18F]FLT uptake in cancer cell was not affected by glucose concentration. In physiologic glucose concentration, [18F]FLT uptake in SCC7 cell line was significantly higher than [18F]FDG uptake after 120 minutes incubation. In [18F]FLT PET imaging may not need fasting for preparation before imaging study. (authors)

The radiochemistry of [{sup 18} F]-FDG: the first experience in Mexico; La radioquimica del [{sup 18} F]-FDG: la primera experiencia en Mexico

Energy Technology Data Exchange (ETDEWEB)

Lopez D, F A [Unidad PET-Ciclotron, Facultad de Medicina, UNAM, Av. Universidad 3000, Ciudad Universitaria, Coyoacan, 04500 Mexico, D. F. (Mexico)

2004-07-01

The present work describes the more used method for the synthesis of 2 - [{sup 18} F] - fluorine-2-deoxy-D-glucose that is the more used radiopharmaceutical in the nuclear medicine in the cancer diagnostic. The process consists on two chemical reactions: i) [{sup 18} F{sup -}] - nucleophilic radio fluorination and i i) a hydrolysis catalyzed by acid. The first reaction incorporates to the [{sup 18} F]- fluorine labelled inside the organic precursor 1,3,4,6-tetra- O -acetil-2- O-trifluoromethanesulfonyl- {beta}-D-mannopyranose (triflate of mannose). The mechanism of this reaction is a bimolecular nucleophilic substitution (SN{sub 2}) with the ion [{sup 18} F{sup -}] - fluoride; in the second reaction, the hydrolysis of those protective acetyl groups generate the hydroxyl groups free of the [{sup 18} F]-FDG. The process includes an azeotropic distillation and several purification steps. (Author)

PET radiochemistry: synthesis of 2-[{sup 18} F]-fluorine-2-deoxy-D-glucose; Radioquimica PET: sintesis de 2-[{sup 18} F]-fluor-2-desoxi-D-glucosa

Energy Technology Data Exchange (ETDEWEB)

Lopez D, F A; Flores M, A; Zarate M, A; Romo, E [Unidad PET-Ciclotron, Facultad de Medicina, UNAM, Ciudad Universitaria, 04510 Mexico D.F. (Mexico)

2005-07-01

The present work describes the method for the synthesis of the 2-[{sup 18}F]-fluorine-2-deoxy-D-glucose, the radiopharmaceutical of more use in nuclear medicine for the diagnosis of cancer at world level. (Author)

Initial results of hypoxia imaging using 1-{alpha}-d-(5-deoxy-5-[{sup 18}F]-fluoroarabinofuranosyl)-2-nitroimidazole ({sup 18}F-FAZA)

Energy Technology Data Exchange (ETDEWEB)

Postema, Ernst J.; McEwan, Alexander J.B.; Riauka, Terence A.; Kumar, Piyush; Richmond, Dacia A.; Abrams, Douglas N. [University of Alberta, Department of Oncology, Edmonton, Alberta (Canada); Wiebe, Leonard I. [University of Alberta, Faculty of Pharmacy and Pharmaceutical Sciences, Edmonton, Alberta (Canada)

2009-10-15

Tumour hypoxia is thought to play a significant role in the outcome of solid tumour therapy. Positron emission tomography (PET) is the best-validated noninvasive technique able to demonstrate the presence of hypoxia in vivo. The locally developed PET tracer for imaging hypoxia, 1-{alpha}-d-(5-deoxy-5-[{sup 18}F]-fluoroarabinofuranosyl)-2-nitroimidazole ({sup 18}F-FAZA), has been shown to accumulate in experimental models of tumour hypoxia and to clear rapidly from the circulation and nonhypoxic tissues. The safety and general biodistribution patterns of this radiopharmaceutical in patients with squamous cell carcinoma of the head and neck (HNSCC), small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC), malignant lymphoma, and high-grade gliomas, were demonstrated in this study. Patients with known primary or suspected metastatic HNSCC, SCLC or NSCLC, malignant lymphoma or high-grade gliomas were dosed with 5.2 MBq/kg of {sup 18}F-FAZA, then scanned 2-3 h after injection using a PET or PET/CT scanner. Images were interpreted by three experienced nuclear medicine physicians. The location and relative uptake scores (graded 0 to 4) of normal and abnormal {sup 18}F-FAZA biodistribution patterns, the calculated tumour-to-background (T/B) ratio, and the maximum standardized uptake value were recorded. Included in the study were 50 patients (32 men, 18 women). All seven patients with high-grade gliomas showed very high uptake of {sup 18}F-FAZA in the primary tumour. In six out of nine patients with HNSCC, clear uptake of {sup 18}F-FAZA was observed in the primary tumour and/or the lymph nodes in the neck. Of the 21 lymphoma patients (15 with non-Hodgkin's lymphoma and 6 with Hodgkin's disease), 3 demonstrated moderate lymphoma-related uptake. Of the 13 lung cancer patients (12 NSCLC, 1 SCLC), 7 had increased {sup 18}F-FAZA uptake in the primary lung tumour. No side effects of the administration of {sup 18}F-FAZA were observed. This study suggests

Radiopharmaceutical research: trends and novel concepts

International Nuclear Information System (INIS)

Wuest, F.

2005-01-01

The efficiency of nuclear medicine in diagnosis, therapy and medicinal research strongly depends on the progress to develop novel suitable radiopharmaceuticals. The selection, preparation, and preclinical evaluation of new radiopharmaceuticals is addressed by the field of radiopharmaceutical chemistry. The rapid developments in the field of biotechnology in the post-genome era combined with the recent advances in the instrumentation of SPECT and PET have directed radiopharmaceutical research into a complex chemical science. Current radiopharmaceutical research comprises novel developments of coordination chemistry with [ 99m Tc]technetium pharmaceuticals, the development of non-standard PET radionuclides and the synthesis of 11 C- and 18 F-labelled radiopharmaceuticals at high specific radioactivity. Further developments deal with an increasing alignment to radiotherapeutics and the implementation of PET into the process of drug development and evaluation. (orig.)

The radiochemistry of [18 F]-FDG: the first experience in Mexico

International Nuclear Information System (INIS)

Lopez D, F.A.

2004-01-01

The present work describes the more used method for the synthesis of 2 - [ 18 F] - fluorine-2-deoxy-D-glucose that is the more used radiopharmaceutical in the nuclear medicine in the cancer diagnostic. The process consists on two chemical reactions: i) [ 18 F - ] - nucleophilic radio fluorination and i i) a hydrolysis catalyzed by acid. The first reaction incorporates to the [ 18 F]- fluorine labelled inside the organic precursor 1,3,4,6-tetra- O -acetil-2- O-trifluoromethanesulfonyl- β-D-mannopyranose (triflate of mannose). The mechanism of this reaction is a bimolecular nucleophilic substitution (SN 2 ) with the ion [ 18 F - ] - fluoride; in the second reaction, the hydrolysis of those protective acetyl groups generate the hydroxyl groups free of the [ 18 F]-FDG. The process includes an azeotropic distillation and several purification steps. (Author)

Fast and repetitive in-capillary production of [18F]FDG

International Nuclear Information System (INIS)

Wester, Hans-Juergen; Schoultz, Bent Wilhelm; Hultsch, Christina; Henriksen, Gjermund

2009-01-01

The increasing demand for radiopharmaceuticals to be provided reproducibly and flexibly with high frequency for clinical application and animal imaging would be better met by improved or even new strategies for automated tracer production. Radiosynthesis in microfluidic systems, i.e. narrow tubing with a diameter of approximately 50-500 μm, holds promise for providing the means for repetitive multidose and multitracer production. In this study, the performance of a conceptually simple microfluidic device integrated into a fully automated synthesis procedure for in-capillary radiosynthesis (ICR) of clinical grade [ 18 F]FDG was evaluated. The instrumental set-up consisted of pumps for reagent and solvent delivery into small mixing chambers, μ-fluidic capillaries, in-process radioactivity monitoring, solid-phase extraction and on-column deprotection of the 18 F-labelled intermediate followed by on-line formulation of [ 18 F]FDG. In-capillary 18 F-fluorination of 2.1 μmol 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulphonyl-beta-d-mannopyranose (TATM; precursor for [ 18 F]FDG) in acetonitrile (MeCN) at a flow rate of 0.3 ml/min within 40 s and subsequent on-line hydrolysis of the intermediate by treatment with 0.3 M NaOH for 1 min at 40 C resulted in a radiochemical yield of 88 ± 4% within 18 F-fluorination was demonstrated by eight independent, sequentially performed ICRs which provided identical tracer quality (radiochemical purity >97%, MeCN 18 F]FDG with remarkably high efficiency and high yield under fully automated conditions. Although the results concerning the levels of activity need to be confirmed after installation of the equipment in a suitable GMP hot-cell environment, we expect the instrumental design to allow up-scaling without major difficulties or fundamental restrictions. Furthermore, we are convinced that similar or nearly identical procedures, and thus instrumentation, will allow ICR of other 18 F-labelled radiopharmaceuticals. (orig.)

Knowledge-based automated radiopharmaceutical manufacturing for Positron Emission Tomography

International Nuclear Information System (INIS)

Alexoff, D.L.

1991-01-01

This article describes the application of basic knowledge engineering principles to the design of automated synthesis equipment for radiopharmaceuticals used in Positron Emission Tomography (PET). Before discussing knowledge programming, an overview of the development of automated radiopharmaceutical synthesis systems for PET will be presented. Since knowledge systems will rely on information obtained from machine transducers, a discussion of the uses of sensory feedback in today's automated systems follows. Next, the operation of these automated systems is contrasted to radiotracer production carried out by chemists, and the rationale for and basic concepts of knowledge-based programming are explained. Finally, a prototype knowledge-based system supporting automated radiopharmaceutical manufacturing of 18FDG at Brookhaven National Laboratory (BNL) is described using 1stClass, a commercially available PC-based expert system shell

PET radiochemistry: synthesis of 2-[18 F]-fluorine-2-deoxy-D-glucose

International Nuclear Information System (INIS)

Lopez D, F.A.; Flores M, A.; Zarate M, A.; Romo, E.

2005-01-01

The present work describes the method for the synthesis of the 2-[ 18 F]-fluorine-2-deoxy-D-glucose, the radiopharmaceutical of more use in nuclear medicine for the diagnosis of cancer at world level. (Author)

Quantification of the whole-body distribution of PET radiopharmaceuticals, applied to 3-N-([18F]fluoroethyl)spiperone

International Nuclear Information System (INIS)

Herzog, H.; Kuwert, T.; Langen, K.J.; Feinendegen, L.E.; Coenen, H.H.

1990-01-01

Using a multi slice whole body PET scanner PC4096-15WB, diagnostic measurements of the cerebral distribution of the D 2 receptor ligand 3-N-([ 18 F]fluoroethyl)spiperone were extended to quantify the biodistribution of this PET radiopharmaceutical. As a rotating line source was used for measured attenuation correction, transmission scans could be combined with emission scans even after injection of the tracer. Only 1% of the total administered dose (TAD) was found in the whole brain at 180 min, but the striatum and pituitary were still excellently delineated. Urinary bladder, gall bladder, and liver were the organs with the highest TAD ranging from 6% to 25%. The gall bladder is the critical organ with an absorbed dose of about 200 mGy/kBq followed by the urinary bladder and liver with 83 and 66 mGy/kBq, respectively. In the rest of the body radioactivity was evenly distributed. The total body dose was found to be 11.9 mGy/kBq. (orig.)

Synthesis, quality control and dosimetry of the radiopharmaceutical 18F-sodium fluoride produced at the Center for Development of Nuclear Technology - CDTN

Directory of Open Access Journals (Sweden)

Marina Bicalho Silveira

2010-09-01

Full Text Available 18F-Sodium fluoride (Na18F is a radiopharmaceutical used for diagnosis in nuclear medicine by positron emission tomography (PET imaging. Bone scintigraphy is normally performed using 99mTc-MDP. However, 18F PET scans promise high quality imaging with increased resolution and improved sensitivity and specificity. In order to make available a tool for more specific studies of tumors and non-oncological diseases of bone tissue, the UPPR/CDTN team undertook the production and quality control of Na18F injectable solution with the physical-chemical, microbiological and biological characteristics recommended in the U.S. Pharmacopeia. Na18F radiochemical purity was 96.7 ± 1.3 %, with Rf= 0.026 ± 0.006. The product presented a pH of 5.3 ± 0.6, half life of 109.0 ± 0.8 minutes, endotoxin limit O Fluoreto de sódio 18F (Na18F é um radiofármaco empregado para diagnóstico através da Tomografia por Emissão de Pósitrons (PET. Cintilografias ósseas são normalmente obtidas utilizando-se 99mTc-MDP. Entretanto, o interesse pelo Na18F é crescente, principalmente devido à obtanção de imagens de elevada resolução. Com o objetivo de tornar disponível uma ferramenta mais específica para estudos de tumores e doenças não-oncológicas do tecido ósseo, o grupo da UPPR/CDTN implementou a produção e o controle de qualidade da solução injetável de Na18F com as características físico-química, microbiológica e biológica preconizadas pela farmacopéia. Sua pureza radioquímica foi de 96,7 ± 1,3 %, com Rf= 0,026 ± 0,006. O produto apresentou pH igual a 5,3 ± 0,6, tempo de meia-vida de 109,0 ± 0,8 minutos, limite de endotoxinas < 5,0 EU.mL-1 e ausência de microrganismos. O perfil de biodistribuição em camundongos foi semelhante ao disponível na literatura, com depuração igual a 0,19 mL.min-1 e volume de distribuição igual a 18,76 mL. A concentração máxima (5,0 ± 0,5 % DI.g-1 foi observada no osso 20 minutos após a injeção. O Na18

Fast and repetitive in-capillary production of [18F]FDG.

Science.gov (United States)

Wester, Hans-Jürgen; Schoultz, Bent Wilhelm; Hultsch, Christina; Henriksen, Gjermund

2009-04-01

The increasing demand for radiopharmaceuticals to be provided reproducibly and flexibly with high frequency for clinical application and animal imaging would be better met by improved or even new strategies for automated tracer production. Radiosynthesis in microfluidic systems, i.e. narrow tubing with a diameter of approximately 50-500 microm, holds promise for providing the means for repetitive multidose and multitracer production. In this study, the performance of a conceptually simple microfluidic device integrated into a fully automated synthesis procedure for in-capillary radiosynthesis (ICR) of clinical grade [(18)F]FDG was evaluated. The instrumental set-up consisted of pumps for reagent and solvent delivery into small mixing chambers, micro-fluidic capillaries, in-process radioactivity monitoring, solid-phase extraction and on-column deprotection of the (18)F-labelled intermediate followed by on-line formulation of [(18)F]FDG. In-capillary(18)F-fluorination of 2.1 micromol 1,3,4,6-tetra-O-acetyl-2-O-trifluoromethanesulphonyl-beta-D-mannopyranose (TATM; precursor for [(18)F]FDG) in acetonitrile (MeCN) at a flow rate of 0.3 ml/min within 40 s and subsequent on-line hydrolysis of the intermediate by treatment with 0.3 M NaOH for 1 min at 40 degrees C resulted in a radiochemical yield of 88 +/- 4% within 97%, MeCN <5 microg/ml) and similar absolute yields (approximately 1.4 GBq). The described ICR process is a simple and efficient alternative to classic radiotracer production systems and provides a comparatively cheap instrumental methodology for the repetitive production of [(18)F]FDG with remarkably high efficiency and high yield under fully automated conditions. Although the results concerning the levels of activity need to be confirmed after installation of the equipment in a suitable GMP hot-cell environment, we expect the instrumental design to allow up-scaling without major difficulties or fundamental restrictions. Furthermore, we are convinced that

Effect of the dilution factor on {sup 18}FDG and Na{sup 18}F samples for bacterial endotoxin test using PTS (portable test system)

Energy Technology Data Exchange (ETDEWEB)

Silveira, Marina B.; Costa, Flavia M.; Ferreira, Soraya Z., E-mail: mbs@cdtn.b [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Unidade de Pesquisa e Producao de Radiofarmacos

2011-07-01

{sup 18}FDG and Na{sup 18}F are radiopharmaceuticals produced as sterile solutions suitable for intravenous administration, which must contain no more than 175 EV/V. The most commonly used approach to detect endotoxins is the gelclot technique that requires 60 minutes for results. For radiopharmaceuticals containing short-life radionuclides, such as {sup 18}F, there is an increasing interest for faster quality control methods. FDA licensed the Endosafe, PTS, a kinetic chromogenic endotoxin detection system that takes about 15 minutes for results. As other techniques, PTS test is susceptible to interferences which can be solved by product dilution. The aim of this study was to establish the best dilution of {sup 18}FDG and Na{sup 18}F for PTS analysis. Two different dilution factors for {sup 18}FDG and 1:10 for Na{sup 18}F were essayed: 1:10 and 1:100. {sup 18}FDG and Na{sup 18} solutions were prepared by the addition of LAL reagent water. Considering the assay acceptance criteria, the best dilution factor was 1:100 for {sup 18}FDG and 1:10 for Na{sup 18}F. The recovery of the product positive control was 98-12% for {sup 18}FDG 1:100 and 104-120% for Na{sup 18}F 1:10, which were, in both cases, within the specification (50-200%) and very close to 100%. Results obtained with these dilution studies were important to establish the most appropriate and non-interfering dilution factor for {sup 18}FDG and Na{sup 18}F routine endotoxin test. (author)

Radiopharmaceuticals in positron emission tomography: Radioisotope productions and radiolabelling procedures at the Austin and Repatriation Medical Centre

International Nuclear Information System (INIS)

Tochon-Danguy, H.J.; Sachinidis, J.I.; Chan, J.G.; Cook, M.

1997-01-01

Positron Emission Tomography (PET) is a technique that utilizes positron-emitting radiopharmaceuticals to map the physiology, biochemistry and pharmacology of the human body. Positron-emitting radioisotopes produced in a medical cyclotron are incorporated into compounds that are biologically active in the body. A scanner measures radioactivity emitted from a patient's body and provides cross-sectional images of the distribution of these radiolabelled compounds in the body. It is the purpose of this paper to review the variety of PET radiopharmaceuticals currently produced at the Austin and Repatriation Medical Centre in Melbourne. Radioisotope production, radiolabelling of molecules and quality control of radiopharmaceuticals will be discussed. A few examples of their clinical applications will be shown as well. During the last five years we achieved a reliable routine production of various radiopharmaceuticals labelled with the four most important positron-emitters: oxygen-15 (t, 1/2 =2min), nitrogen-13 (t 1/2 = 10 min), carbon-11 (t 1/2 =20 min) and fluorine-18 (t 1/2 = 110 min). These radiopharmaceuticals include [ 15 O]oxygen, [ 15 O]carbon monoxide, [ 15 O]carbon dioxide, [ 15 O]water, [ 13 N]ammonia, [ 11 C]flumazenil, [ 11 C]SCH23390, [ 18 F]fluoromisonidazole and [ 18 F]fluoro-deoxy-glucose ([ 18 F]FDG). In addition, since the half life of [ 18 F] is almost two hours, regional distribution can be done, and the Austin and Repatriation Medical Centre is currently supplying [ 18 F]FDG in routine to other hospitals. Future new radiopharmaceuticals development include a [ 18 F]thymidine analog to measure cell proliferation and a [ 11 C]pyrroloisoquinoline to visualize serotonergic neuron abnormalities. (authors)

An improved radiosynthesis of the muscarinic M2 radiopharmaceutical, [18F]FP-TZTP

International Nuclear Information System (INIS)

Oosten, Erik M. van; Wilson, Alan A.; Stephenson, Karin A.; Mamo, David C.; Pollock, Bruce G.; Mulsant, Benoit H.; Yudin, Andrei K.; Houle, Sylvain; Vasdev, Neil

2009-01-01

The radioligand 3-(4-(3-[ 18 F]fluoropropylthio)-1,2,5-thiadiazol-3-yl)-1-methyl-1,2,5, 6-tetrahydropyridine ([ 18 F]FP-TZTP) is an agonist with specificity towards subtype 2 of muscarinic acetylcholine (M2) receptors. It is currently the only radiotracer available for imaging M2 receptors in human subjects with positron emission tomography. The present study reports on an improved method for the synthesis of [ 18 F]FP-TZTP, automated using a GE TRACERlab TM FX FN radiosynthesis module. A key facet was the use of a new precursor, 3-(4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazol-3-ylthio) propyl 4-methylbenzenesulfonate. The precursor was fluorinated via nucleophilic displacement of the tosyloxy group by potassium cryptand [ 18 F]fluoride (K[ 18 F]/K 222 ) in CH 3 CN at 80 deg. C for 5 min, and purified by HPLC. Formulated [ 18 F]FP-TZTP was prepared in an uncorrected radiochemical yield of 29±4%, with a specific activity of 138±41 GBq/μmol (3732±1109 mCi/μmol) at the end of synthesis (35 min; n=3). This methodology offers higher yields, faster synthesis times, an optimized precursor, and simpler automation than previously reported

Stability study of 2-[18F]Fluoro-2-Deoxy-D-Glucose (18FDG) stored at room temperature by physicochemical and microbiological assays

International Nuclear Information System (INIS)

Ferreira, Soraya Z.; Silva, Juliana B. da; Waquil, Samira S.; Correia, Ricardo F.

2009-01-01

The most widely used radiopharmaceutical in the expanding medical imaging technology of Positron Emission Tomography (PET) is 2-[ 18 F]fluoro-2-deoxy-D-glucose ( 18 FDG). The increasing demand for 18 FDG requires reliable production in large amounts. The synthesis of 18 FDG is based on a nucleophilic substitution of the triflate-leaving group from the precursor, mannose triflate, in the presence of Crypt and 2.2.2, as a phase-transfer agent. After labeling, the removal of the acetyl protecting groups from resulting 2-[ 18 F]fluoro-1,3,4,6-tetra-Oacetyl- D-glucose is performed by alkaline hydrolysis, followed by purification and final filtration (0.22 μm). It was reported that 18 FDG decomposes in vitro, resulting in the degradation of the radiochemical purity with time. The aim of this study was to evaluate physicochemical and microbiological stability of 18 FDG, stored at room temperature (15-30 deg C), at different time intervals. It was investigated how the quality of this radiopharmaceutical varies with time under the influence of environmental factors. 18 FDG pH, radionuclidic identity and purity, radiochemical identity and purity, chemical purity, residual solvents, bacterial endotoxins and sterility were evaluated according to the United States Pharmacopeia 31 th edition analytical methods and acceptance criteria. The results suggest that 18 FDG has physicochemical and microbiological stability up to 10 hours after the end of synthesis, under experimental conditions. (author)

Radiopharmaceuticals and applications; Preparacoes radiofarmaceuticas e suas aplicacoes

Energy Technology Data Exchange (ETDEWEB)

Oliveira, Rita [Universidade Fernando Pessoa, Porto (Portugal). Fac. de Ciencias da Saude; Santos, Delfim; Ferreira, Domingos; Coelho, Pedro [Universidade do Porto (Portugal). Fac. da Farmacia; Veiga, Francisco, E-mail: fveiga@ci.uc.pt [Universidade de Coimbra (Portugal). Fac. de Farmacia

2006-04-15

Radiopharmaceuticals are substances without pharmacological activity that are used in Nuclear Medicine for diagnosis and therapy for several diseases. Diagnosis radiopharmaceuticals generally emit {gamma} radiation or positrons ({beta}+), because their decay originates penetrating electromagnetic radiation that can cross the tissues and be externally detected. Therapeutic radiopharmaceuticals must include in their composition ionized particles emission nucleus ({alpha}, {beta}{sup -} or Auger electrons), since their action is based in selective tissue destruction. There are two main methods for image acquisition: SPECT (Single Photon Emission Computerized Tomography) that uses {gamma} emission radionuclides ({sup 99m}Tc, {sup 123}I, {sup 67}Ga, {sup 201}Tl) and PET (Positron Emission Tomography) that uses positron emission radionuclides like {sup 11}C, {sup 13}N, {sup 15}O, {sup 18}F. Radiopharmaceuticals can be classified into perfusion radiopharmaceuticals (first generation) or specific radiopharmaceuticals (second generation). Perfusion radiopharmaceuticals are transported in the blood e reach the target organ in the direct proportion of the blood stream. Specific radiopharmaceuticals contain a biologically active molecule that binds to cellular receptors that must remain biospecific after binding to the radiopharmaceutical. For this type of radiopharmaceuticals, tissue or organ uptake is determined by the biomolecule capacity of recognizing receptors in those biological structures. Radiopharmaceuticals are produced ready to use, in cold kits or in autologal preparations. According to the preparation type there is a different quality control procedure. Most of the radiopharmaceuticals used nowadays are of the perfusion type. Research focus in the development of specific radiopharmaceuticals that can provide information, at the molecular level, of biochemical alterations associated to different pathologies. (author)

Radiopharmaceuticals in positron emission tomography: Radioisotope productions and radiolabelling procedures at the Austin and Repatriation Medical Centre

Energy Technology Data Exchange (ETDEWEB)

Tochon-Danguy, H.J.; Sachinidis, J.I.; Chan, J.G.; Cook, M. [Austin and Repatriation Medical Centre, Melbourne, VIC (Australia). Centre for Positron Emission Tomography

1997-10-01

Positron Emission Tomography (PET) is a technique that utilizes positron-emitting radiopharmaceuticals to map the physiology, biochemistry and pharmacology of the human body. Positron-emitting radioisotopes produced in a medical cyclotron are incorporated into compounds that are biologically active in the body. A scanner measures radioactivity emitted from a patient`s body and provides cross-sectional images of the distribution of these radiolabelled compounds in the body. It is the purpose of this paper to review the variety of PET radiopharmaceuticals currently produced at the Austin and Repatriation Medical Centre in Melbourne. Radioisotope production, radiolabelling of molecules and quality control of radiopharmaceuticals will be discussed. A few examples of their clinical applications will be shown as well. During the last five years we achieved a reliable routine production of various radiopharmaceuticals labelled with the four most important positron-emitters: oxygen-15 (t,{sub 1/2}=2min), nitrogen-13 (t{sub 1/2}= 10 min), carbon-11 (t{sub 1/2}=20 min) and fluorine-18 (t{sub 1/2}= 110 min). These radiopharmaceuticals include [{sup 15}O]oxygen, [{sup 15}O]carbon monoxide, [{sup 15}O]carbon dioxide, [{sup 15}O]water, [{sup 13}N]ammonia, [{sup 11}C]flumazenil, [{sup 11}C]SCH23390, [{sup 18}F]fluoromisonidazole and [{sup 18}F]fluoro-deoxy-glucose ([{sup 18}F]FDG). In addition, since the half life of [{sup 18}F] is almost two hours, regional distribution can be done, and the Austin and Repatriation Medical Centre is currently supplying [{sup 18}F]FDG in routine to other hospitals. Future new radiopharmaceuticals development include a [{sup 18}F]thymidine analog to measure cell proliferation and a [{sup 11}C]pyrroloisoquinoline to visualize serotonergic neuron abnormalities. (authors) 23 refs., 2 tabs.

Standardization of {sup 123}I and {sup 18}F for providing traceability of activity meters performed in the Radiopharmaceutical Production Service of the Instituto de Engenharia Nuclear, RJ, Brazil; Padronizacao do Iodo-123 e Fluor-18 para provimento de rastreabilidade das medicoes de atividade realizadas no Servico de Producao de Radiofarmacos do Instituto de Engenharia Nuclear

Energy Technology Data Exchange (ETDEWEB)

Andrade, E.A.L., E-mail: erica@ien.gov.br [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Delgado, J.U.; Iwahara, A.; Contic, C.C., E-mail: delgado@ird.gov.br, E-mail: iwahara@ird.gov.br, E-mail: ccconti@ird.gov.br [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

2013-07-01

The commercialization and use of radiopharmaceuticals in Brazil are regulated by Sanitary Vigilance National Agency which requiring Good Manufacturing Practices certification for all segments within the Nuclear Medicine. Quality Assurance Programmes should implement the standard requirements to ensure that radiopharmaceuticals have requirements quality to proving its efficiency. Several aspects should be controlled, and one of them is the traceability of the Radionuclides Activity Measurement in radiopharmaceuticals doses. This paper aims to provide traceability to dose calibrators (well type ionization chambers) used for {sup 123}I and {sup 18}F activity measurements in Radiopharmaceuticals Production Service placed in Institute of Nuclear Engineering, Rio de Janeiro, RJ, Brazil. (author)

Analysis of residual solvents in PET radiopharmaceuticals by GC

International Nuclear Information System (INIS)

Li Yungang; Zhang Xiaojun; Liu Jian; Tian Jiahe; Zhang Jinming

2013-01-01

The residual solvents in PET radiopharmaceuticals were analyzed by GC, which were acetonitrile, ethanol, N, N-dimethylethanolamine (DMEA), dimethylsulfoxide (DMSO). The standard curves were established with the AT-624 capillary column at GC, and the sensitivity of acetonitrile and ethanol were 0.004-0.320 g/L and 0.010-0.120 g/L respectively. The residual solvents of acetonitrile, ethanol, DMEA and DMSO in PET radio- pharmaceuticals were analyzed by GC. The linearity were 0.9994, 0.9999, 0.9997, 0.999 6 respectively. The residual of acetonitrile were (0.0313±0.0433), (0.0829±0.0668), (0.0156±0.0059), (0.0254±0.0266) g/L in 18 F-FDG, 18 F-FLT, 11 C-CFT, 11 C-PIB respectively. The residual of ethanol was (0.0505±0.00528) g/L in 18 F-FDG. The residual of DMSO were (0.0331±0.0180) g/L, (0.0238±0.0100) g/L in 18 F-W372 and 11 C-DTBZ respectively. The residual of DMEA was (0.0348±0.0022) g/L in 11 C-Choline. The survived of organic solvent in PET radiopharmaceuticals can be analyzed with GC directly. The results showed that the QC should be done in PET radiopharmaceuticals purity with semi-HPLC to avoid the high residual. (authors)

Productions and interests of the radiopharmaceuticals labelled by 11C, 13N, 15O, and 18F

International Nuclear Information System (INIS)

Blanc-Borras, Louisette

1985-01-01

As medical diagnosis methods based on the use of short-life radioelements such as carbon-11, nitrogen-13, oxygen-15 and fluorine-18 have been developed, these four radio-isotopes are notably adapted to external detection by tomography. Besides, due to their short period, their radioactive concentration per mass unity is very high. In the first part of this research thesis, the author presents the characteristics of these four radio-isotopes, describes the operation of cyclotrons and the principles, benefits, drawbacks, and types of positron emission tomography. The second part addresses the production of the radionuclides and precursors, the production of radiopharmaceutical products (haemoglobin, sugars, amino acids, fatty acids, steroid marking, and drug marking). The third part reports some studies illustrating the pharmaceutical interest of these radioelements [fr

Incorporation study of 18FDG through its uptake into tumour-derived cell lines

International Nuclear Information System (INIS)

Costa, Flavia M.; Nascimento, Leonardo T.C.; Santos, Raquel G.

2013-01-01

In vitro tests of radiopharmaceuticals are an important instrument to study their mechanisms of action, binding and incorporation. 18 FDG is the most used radiopharmaceutical for diagnostics positron emission tomography (PET) on oncology, on the basis of accelerated rates of absorption of glucose in cell malignancies. This radiotracer has been routinely produced at CDTN; and therefore, it was selected for preliminary assays due to its availability. Nowadays, UPPR at CDTN produces routinely 18 FDG for the local PET Centers but others PET radiopharmaceuticals are in development such as 18 F-Fluorocholine and 18 F-Fluorothymidine. According to the Brazilian Health Regulatory Agency (ANVISA) it is necessary to validate and register these new radiopharmaceuticals in order to get the approval for their commercialization. Targeting efficacy is one of the important issues to be evaluated during radiopharmaceutical validation. The aim of this study was to develop a standard protocol to determine tumor targeting efficacy of PET radiopharmaceuticals in vitro. Therefore it was developed a protocol based on the incorporation og 18 FDG through the uptake in different tumor-derived cell lines. Three variables were investigated for the standardization of the test: the number of cells to be seeded in 96-well plates, the time of incubation with the radiopharmaceutical and the radiotracer concentration. The standardized protocol was considered suitable for 18 FDG incorporation assay and showed reproductive results. The protocol developed in this work will pave the way for the in vitro studies of incorporation of the new PET radiopharmaceuticals to be produced at UPPR-CDTN, such as: 18 F-Fluorocholine and 18 F-Fluorothymidine. (author)

Calibration of F-18 activity for PET applications in Cuba

International Nuclear Information System (INIS)

León, Yecenia Moreno; Verdecia, Pilar Oropesa; Rodríguez, Lourdes García; Águila, Rolando A. Serra; Magaña, Yoel Jénez; Hechavarría, Ailec Bell; Pérez, Nayla; Cacero, Maray Dubalón; Ruiz, Javier Mas

2016-01-01

In the paper we present the results of the calibration of the concentration of F-18 dissolution activity in Cuba. Methods of measurement in a calibrated well ionization chamber, traceable to the UK national standard and gamma spectrometry yielded equivalent results within the limit of the associated uncertainties, respectively. The measurement uncertainties of the F-18 activity of the secondary standard activity activator, CAPINTEC CRCTM 15R, obtained from calibration of the instrument with the calibrated solutions of radionuclide, are also shown for the measurement of samples in the geometries of interest in Nuclear Medicine: glass jars and plastic syringes. The results presented in this paper constitute the necessary metrological support for the use of F-18 radiopharmaceuticals and the new PET and PET / CT technologies in medical practice in Cuba.

Semi-automatic synthesis and biological evaluation of 18F-FCH as an oncologic PET tracer

International Nuclear Information System (INIS)

Wu Zhanhong; Wang Shizhen; Zhou Qian; Fu Zhe; Qiu Feichan; Huo Li

2005-01-01

18 F-fluromethylcholine ( 18 F-FCH) as a PET tracer is synthesized. The semi-automatic synthesis assembly of 18 F-FCH is modified from CPCU(CTI). The radiochemical purity is measured by analytical HPLC. The radiochemical yield and the radiochemical purity of 18 F-FCH are 15% and >99%, respectively. The total radiosynthesis time is 55 min after EOB. The labeled product exhibited low toxicity. The biodistribution in normal mice and the toxicity are studied. PET imaging with 18 F-FCH is performed on tumor xenograft murine model. The semi-automatic synthesis assembly is promising to be used for routine clinic radiopharmaceutical preparation and preliminary study has shown the usefulness of 18 F-FCH as an oncologic PET tracer. (authors)

[F-18] halofluorination: A rapid and efficient method for the incorporation of radiofluorine into organic molecules

International Nuclear Information System (INIS)

Chi, D.Y.; Katzenellenbogen, J.A.; Kilbourn, M.R.; Welch, M.J.

1985-01-01

The addition of halogen fluoride to olefins (Hal-F, halofluorination, where Hal is Br or I) is a more favorable reaction for labeling with tracer levels of F-18 than is addition of hydrogen fluoride (H-F, hydrofluorination), because of the more productive soft acid-soft base interaction between the Hal and the olefin. The authors have found that simple olefins (allylbenzene, 1-hexene, 1-propene) undergo rapid bromofluorination when treated with 1,3-dibromo-5,5-dimethylhydantoin (DBH), giving a 7:1 mixture of Markownikow (M) and anti-Markownikow (AM) adducts. In chlorinated solvents, the reaction is rapid and efficient, giving yields of 50-90% based on fluoride as limiting reagent. The products can be reduced to the fluorocarbon by debromination (R/sub 3/SnH or LiAlH/sub 4/), or they can be used to alkylate amines. Reasonable radiochemical yields can be obtained using F-18 produced in a water target [/sup 18/O(p,n)/sup 18/F], in either carrier-added (20-50%) or no-carrier-added (ca. 10-20%) modes. This reaction is being used to prepare F-18 labeled radiopharmaceuticals

Comparison of C-11-choline and F-18-FDG PET in primary diagnosis and staging of patients with thoracic cancer

NARCIS (Netherlands)

Pieterman, RM; Que, TH; Elsinga, PH; Pruim, J; van Putten, JWG; Willemsen, ATM; Vaalburg, W; Groen, HJM

PET with F-18-FDG is used for detection and staging of thoracic cancer; however, more specific PET radiopharmaceuticals would be welcome. C-11-labeled choline (CHOL) is a new radiopharmaceutical potentially useful for tumor imaging, since it is incorporated into cell membranes as

Mapping of functional activity in brain with 18F-fluoro-deoxyglucose

International Nuclear Information System (INIS)

Alavi, A.; Reivich, M.; Greenberg, J.; Wolf, A.

1981-01-01

A model has been designed based on the assumptions of a steady state for glucose consumption, a first-order equilibration of the free 14 C-DG pool in the tissue with the plasma level, and relative rates of phosphorylation of 14 C-DG and glucose determined by their kinetic constants for hexokinase reaction. Using an operational equation based on this model, the metabolic rates of glucose are calculated in various regions of brain (utilizing brain slices and autoradiography). 14 C is a beta emitter and therefore not suitable for noninvasive imaging in man. With the synthesis of 18 F-2-deoxy-2-fluoro-D-glucose ( 18 F-DG) all of the requirements for a suitable radiopharmaceutical for the determination of local cerebral metabolism have been met. This agent behaves very similarly to 14 C-DG and therefore, using the above described model and emission tomography, it has become possible to measure regional cerebral metabolism for the first time in man

Proposals for implementation of methodological aspects in the use of 18F-FDG in the Positron Emission Tomography

International Nuclear Information System (INIS)

Oliveira, Cássio Miri

2013-01-01

This work covered three objectives: to evaluate and implement methods for in vivo internal occupational monitoring of individuals involved during the 18 F-FDG process production; to suggest a national Diagnostic Reference Level (DRL) for 18 F-FDGPET oncologic procedures; and to obtain the 'Recovery Coefficients' (RCs) factors used to correct the radiopharmaceutical uptake in region of interest for a better quantification and evaluation of images. The methodology of internal monitoring was implemented in the radiopharmaceuticals production centers of Nuclear Technology Development Center (CDTN) in Belo Horizonte - MG and the Nuclear Science Regional Center, North-East (CRCN-NE) in Recife, PE, Brazil. The results demonstrated that the developed methodology was efficient to evaluate 18 F-FDG incorporations in both centers; additionally, the methodology showed that there was possibility of 18 F incorporation in the form of 18 F-FDG during non-routine actions performed in the radiopharmaceutical production process. DRLs were suggested based on a questionnaire that was used for the survey of 18 F-FDG administered activity in 72 Brazilian clinics currently licensed by the National Nuclear Energy Commission (CNEN). The results reported by 41 (57%) of the 18 F-FDG-PET clinics showed variations up to 100% in the administered activities among clinics for the same procedure. The calculated DRL from the third quartile was 5.54 MBq/kg or 387.7 MBq (for a 70 kg standard patient). For image analysis, two phantoms were used for obtaining the RCs, the NEMA/IEC Body Phantom, which has spherical capture areas and the modified Jaszczak, which has cylindrical capitation capture areas. Both phantoms were tested for different lesion:BG activity ratios, in the amount of 4:1 and 10:1; for different acquisition time. RCs obtained according to NEMA and IEC standards were applied to the SUVmax and SUVmed semi quantification tools. Values of SUVmed corrected by RCs presented

Design of an Automated System for Synthesis of [18 F] FDG for PET Investigation at IFIN-HH Bucharest

International Nuclear Information System (INIS)

Craciun, Liviu Stefan; Cimpeanu, Catalina; Constantinescu, Olimpiu; Dudu, Dorin; Ionescu, Cristina; Negoita, Nicolae; Racolta, Petru Mihai; Rusen, Ion

2009-01-01

A novel apparatus constructed at IFIN-HH is described for automated synthesis of radiopharmaceuticals labeled with 18 F for use in positron emission tomography (PET) investigations. [18 F] fluoride was produced at the IFIN-HH cyclotron by irradiation of H 2 O enriched 97% in 18 O with 13 MeV deuterons, or 8 MeV protons. The irradiated H 2 O was transferred (injected) into the radiochemical fully-automated processing systems which ensured the separation of 18 F from H 2 O, the labeling with 18 F, and finally purified by filtration with selective absorbants. The system is easy to operate and contains a programmable logical controller that manages the entire operation program stored in its internal memory. The computer is used to assist the operator during the different steps of synthesis and to allow visualization of the process and printing the report. The device was used for used for the production of 2-[18 F] FLUORO-2-DEOXY-D-GLUCOSE at the IFIN-HH cyclotron, one of the most used radiopharmaceutical in PET investigations. The synthesis module is configured so that is flexible enough to accomplish other nucleophile reactions of labeling with short lived radioisotopes.

Design of an Automated System for Synthesis of [18 F] FDG for PET Investigation at IFIN-HH Bucharest

Science.gov (United States)

Craciun, Liviu Stefan; Cimpeanu, Catalina; Constantinescu, Olimpiu; Dudu, Dorin; Ionescu, Cristina; Negoita, Nicolae; Racolta, Petru Mihai; Rusen, Ion

2009-03-01

A novel apparatus constructed at IFIN-HH is described for automated synthesis of radiopharmaceuticals labeled with 18F for use in positron emission tomography (PET) investigations. [18 F] fluoride was produced at the IFIN-HH cyclotron by irradiation of H2O enriched 97% in 18O with 13 MeV deuterons, or 8 MeV protons. The irradiated H2O was transferred (injected) into the radiochemical fully-automated processing systems which ensured the separation of 18F from H2O, the labeling with 18F, and finally purified by filtration with selective absorbants. The system is easy to operate and contains a programmable logical controller that manages the entire operation program stored in its internal memory. The computer is used to assist the operator during the different steps of synthesis and to allow visualization of the process and printing the report. The device was used for used for the production of 2-[18 F] FLUORO-2-DEOXY-D-GLUCOSE at the IFIN-HH cyclotron, one of the most used radiopharmaceutical in PET investigations. The synthesis module is configured so that is flexible enough to accomplish other nucleophile reactions of labeling with short lived radioisotopes.

Evaluation of 4-[18F]fluoro-1-butyne as a radiolabeled synthon for click chemistry with azido compounds

International Nuclear Information System (INIS)

Kim, Dong Hyun; Choe, Yearn Seong; Kim, Byung-Tae

2010-01-01

Click chemistry is a useful approach for the preparation of novel radiopharmaceuticals. In this study, we evaluated 4-[ 18 F]fluoro-1-butyne as a radiolabeled synthon for click chemistry with azido compounds. Our results showed that nucleophilic substitution of 4-tosyloxy-1-butyne with K[ 18 F]F produces vinyl acetylene as well as 4-[ 18 F]fluoro-1-butyne, while the same reaction using 5-tosyloxy-1-pentyne gives exclusively 5-[ 18 F]fluoro-1-pentyne. Thus, ω-[ 18 F]fluoro-1-alkynes with chain lengths longer than four carbons may be better radiolabeled synthons for use in click chemistry.

Automated production of [18F]FDDNP using a TRACERlab MXFDG

International Nuclear Information System (INIS)

Vercouillie, J.; Maia, S.; Edmond, P.; Guilloteau, D.; Prenant, Ch.; Deloye, J.B.; Maia, S.; Guilloteau, D.; Guillouet, St.; Barre, L.

2010-01-01

[ 18 F]FDDNP has been recently described as a potent tracer to image amyloid plaques in vivo by positron emission tomography. Such a tool will be advisable to diagnose patient with mild cognitive impairment, to follow the disease progression and to evaluate new therapies. To make this radiopharmaceutical affordable for the clinicians, we developed an automated method for [ 18 F]FDDNP radiosynthesis using a commercial [ 18 F]FDG unit. Radiolabeling with fluorine-18 was carried out by a [ 18 F]fluoro-detosylation reaction on the precursor 2-(1-{6-[(2-tosyloxyoethyl)(methyl)amino]-2- naphthyl}ethylidene)malononitrile. The reaction was performed in acetonitrile for 15 min at 90 C, and then the reaction mixture was injected into a semi-preparative high-pressure liquid chromatography. The desire [ 18 F]FDDNP fraction was collected, and an SPE was performed. The [ 18 F]FDDNP was formulated in a sodium chloride/ethanol solution followed by a sterile filtration. Stability of [ 18 F]FDDNP was studied after 4 h and radiochemical purity of [ 18 F]FDDNP remained ≥98%. The overall decay-corrected radiochemical yield was 15±3% (n = 8). Radiochemical purity was ≥98% and the specific activity was 164±25 GBq/μmol at EOS. Pharmaceutical controls, bio-burden, sterility, bacterial endotoxin and residual solvent tests were performed. The results were in accordance with the European Pharmacopoeia and demonstrated our ability to produce [ 18 F]FDDNP with a pharmaceutical grade and a high reproducibility. (authors)

Radiopharmaceuticals labelled with positron-emitting radioisotopes

International Nuclear Information System (INIS)

Comar, D.; Berridge, M.; Maziere, B.; Crouzel, C.

1982-01-01

This chapter reviews the preparation of radioisotopes for biochemical and physiological studies and the principal methods for their incorporation into radiopharmaceuticals, while pointing out the problems encountered with their use and considering their medical interest in the following areas: distribution and flow of fluids, metabolic and pharmacokinetic studies. Inorganic and organic radiopharmaceuticals presently in use and most probable to be used in the future are reviewed. It is anticipated that three types of products labelled with 15 O, 13 N, 11 C and 18 F will be developed in the future. The first type includes products which trace general phenomena such as fluid movement or metabolism of sugars, fats and proteins. The compromise between physiological accuracy and imaging technology is discussed in relation to the use of 11 C and 18 F. The second type of product is one to measure more specific parameters such as those of molecular transport kinetics, membrane permeability, cellular pH and receptor-ligand interactions, again with particular reference to 11 C and 18 F. The third type of product discussed is that intended for pharmacology studies, particular reference being made to 68 Ga, 82 Rb. Extensive bibliography. (U.K.)

An improved radiosynthesis of the muscarinic M2 radiopharmaceutical, [{sup 18}F]FP-TZTP

Energy Technology Data Exchange (ETDEWEB)

Oosten, Erik M. van [Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 (Canada); PET Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Wilson, Alan A.; Stephenson, Karin A. [PET Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Mamo, David C. [PET Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Geriatric Mental Health Program, Centre for Addiction and Mental Health, 1001 Queen Street West, Toronto, Ontario, M6J 1H4 (Canada); Pollock, Bruce G.; Mulsant, Benoit H. [Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Geriatric Mental Health Program, Centre for Addiction and Mental Health, 1001 Queen Street West, Toronto, Ontario, M6J 1H4 (Canada); Yudin, Andrei K. [Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6 (Canada); Houle, Sylvain [PET Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Vasdev, Neil [PET Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada); Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario, M5T 1R8 (Canada)], E-mail: neil.vasdev@camhpet.ca

2009-04-15

The radioligand 3-(4-(3-[{sup 18}F]fluoropropylthio)-1,2,5-thiadiazol-3-yl)-1-methyl-1,2,5, 6-tetrahydropyridine ([{sup 18}F]FP-TZTP) is an agonist with specificity towards subtype 2 of muscarinic acetylcholine (M2) receptors. It is currently the only radiotracer available for imaging M2 receptors in human subjects with positron emission tomography. The present study reports on an improved method for the synthesis of [{sup 18}F]FP-TZTP, automated using a GE TRACERlab{sup TM} FX{sub FN} radiosynthesis module. A key facet was the use of a new precursor, 3-(4-(1-methyl-1,2,5,6-tetrahydropyridin-3-yl)-1,2,5-thiadiazol-3-ylthio) propyl 4-methylbenzenesulfonate. The precursor was fluorinated via nucleophilic displacement of the tosyloxy group by potassium cryptand [{sup 18}F]fluoride (K[{sup 18}F]/K{sub 222}) in CH{sub 3}CN at 80 deg. C for 5 min, and purified by HPLC. Formulated [{sup 18}F]FP-TZTP was prepared in an uncorrected radiochemical yield of 29{+-}4%, with a specific activity of 138{+-}41 GBq/{mu}mol (3732{+-}1109 mCi/{mu}mol) at the end of synthesis (35 min; n=3). This methodology offers higher yields, faster synthesis times, an optimized precursor, and simpler automation than previously reported.

Full Automatic synthesis of [18F]FMISO

International Nuclear Information System (INIS)

Seung Jun Oh; Se Hun Kang; Jin-Sook Ryu; Dae Hyuk Moon

2004-01-01

[ 18 F]FMISO is a radiopharmaceutical for hypoxia imaging. Although it was developed in 1986, there has been no report about automatic synthesis. In this experiment, we established the full automatic synthesis of [ 18 F]FMISO and evaluate the stability according to ICH guideline. Method: We used GE MicroLab MX for automatic synthesis. Sequence program was modified to control of the module as follows: [ 18 F]Fluoride drying→[ 18 F]fluorination→trapping of reaction mixture on C18 cartridge→purification-elution of reaction mixture→hydrolysis and HPLC purification. We used disposable cassette for each synthesis and discard it after synthesis. To find optimal synthesis condition, we tested 90 120 degree C as reaction temperature, 5 15 mg of 1-(2-nitro-1-imidazolyl) -2-O-tetrahtdropyranyl-3-O-toluenesulfonyl-propanediol as precursor and 5 15 min as [ 18 F]fluorination time. HPLC purification condition was EtOH:H20 = 5:95, 5ml/min with Alltech Econosil column. To check the stability of production, we performed 30 times of run. We checked the radiochemical stability until 6 hours at 25 degree C and 40% humidity condition. We also performed the stability test at 50 70 degree C with 60-80% humidity condition or under UV light for 6 hours after synthesis for acceleration test, Results: The optimal [ 18 F] fluorination condition was 10mg of precursor and 15 min incubation at 110 degree C. Hydrolysis was performed at 105 degree C for 5 min. After HPLC purification, radiochemical yields and purity were 45±2.8 and 98±1.2%, respectively. Total synthesis time was 60±5.2 min. [ 18 F]FMISO was stable until 6 hours after production with 97±2.4% of radiochemical purity. [ 18 F]FMISO was also stable in acceleration test and photochemical test with 97±2.4 and 97±2.8% of radiochemical purity, respectively. Conclusion: We established the full automatic synthesis method of [ 18 F]FMISO with reproducible high production yield. [18F]FMISO synthesized by this method was stable

Development of fluorine 18 labelled MPPF, radiopharmaceutical tracer for serotoninergic system exploration

International Nuclear Information System (INIS)

Le Bars, D.; Tochon-Danguy, H.

2002-01-01

Full text: Positron Emission Tomography (PET) is a non-invasive method for exploration, in man and animals, of metabolism with radiopharmaceutical tracers labelled with positron emitters such as carbon 11 and fluorine 18 obtained with a cyclotron. Among the ever increasing number of tracers focussed at the CNS neurotransmission, the discovery of a new family of serotoninergic 5HT 1A antagonists (WAY 100635) has led to the first in vivo imaging of 5HT 1A receptors in man, located in cerebral structures such as cortex and hippocampus. Exploration of serotonine parthway is particulaly interesting in normal or diseased state, as this neurotransmitter is involved in the control of mood, sleep and is probably altered in psychiatric disorders. CERMEP, in collaboration with other PET centres has developped a new 5HT 1A antagonist, MPPF, labelled with fluorine 18. [ 18 F]MPPF has the advantadge of fluorine 18 labelling, with a longer half-life (110 min vs 20 min for carbon 11) and easier radiosynthesis automation. Moreover, MPPF affinity for 5HT 1A is close to serotonin itself, thus enabling displacement of MPPF by endogenous serotonin during pharmacological challenges. Automated radiosynthesis of MPPF is achieved via a classical [ 18 F]F - fluoro for nitro displacement, activated by a catalyst, on a nitro precursor prepared in four steps. A final HPLC purification ensures the production of [ 18 F]MPPF with a high purity and a high specific activity. Ex vivo autoradiographies and PET studies in animals (rat, cat) have shown the excellent specificity of MPPF for the 5HT 1A receptor. Experiments with intracerebral β probe have evidenced the displacement of [ 18 F]MPPF by endogenous serotonin after fenfluramine injection. [ 18 F]MPPF is now used in man for non-invasive PET studies of serotoninergic system. Normal volunteers matched for age and sex have been screened as a database and to compute a mathematical model of the tracer kinetic describing 5HT 1A receptor affinity and

Characterization of atmospheric emissions of a radiopharmaceutical' s production unit

Energy Technology Data Exchange (ETDEWEB)

Siqueira, Gessilane M.; Barreto, Alberto A.; Maletta, Paulo G.M.; Alves, Thaís A.N., E-mail: gessilane.siqueira@cdtn.br, E-mail: aab@cdtn.br, E-mail: pgmm@cdtn.br, E-mail: aryadnenasc@gmail.com [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte - MG (Brazil)

2017-07-01

Cyclotrons are radiative facilities capable of synthesizing radioisotopes that will be used for the production of radiopharmaceuticals. The increasing use of these substances in diagnostic therapies and procedures in nuclear medicine implies the need to increase the production of radiopharmaceuticals. In this context, it is fundamental, from the point of view of environmental radioprotection, to characterize atmospheric emissions from this type of production, in order to make feasible studies of radiological impacts, especially with a view to human health and environmental preservation. It is premise that facilities must ensure the radiological safety of exposed individuals through the control of discharges into the environment. This work aims to characterize the atmospheric emissions behavior of a Radiopharmaceutical Research and Production Unit (RRPU). The emission data for the radionuclides C-11, F-18, and N-13, associated to the production of radiopharmaceuticals ({sup 18}F-FES, {sup 18}F-FDG, {sup 18}FCOL, {sup 18}F-FLT, Na{sup 18}F) during the year 2016 were analyzed. Emissions data are collected every 10 seconds from a sensor installed in the unit's exhaust system. The pre-processing of these data was done by spreadsheets (Excel®) and exported to a statistical package (Minitab16®) to characterize the behavior of these emissions. The results of this study aim to contribute: to the study of atmospheric dispersion of radionuclides in the region of interest; to evaluate the operational control measures of the investigated facility; and to evaluate the radiological impacts in the region neighboring the facility. This methodology has been used in atmospheric dispersion modeling studies in the RRPU and the results showed that the annual doses from the emissions are within the limits established by the radioprotection norms of the Brazilian National Nuclear Energy Commission. Additionally, it is believed that the information generated in this study

Improved GMP-compliant multi-dose production and quality control of 6-[18F]fluoro-L-DOPA.

Science.gov (United States)

Luurtsema, G; Boersma, H H; Schepers, M; de Vries, A M T; Maas, B; Zijlma, R; de Vries, E F J; Elsinga, P H

2017-01-01

6-[ 18 F]Fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) is a frequently used radiopharmaceutical for detecting neuroendocrine and brain tumors and for the differential diagnosis of Parkinson's disease. To meet the demand for FDOPA, a high-yield GMP-compliant production method is required. Therefore, this study aimed to improve the FDOPA production and quality control procedures to enable distribution of the radiopharmaceutical over distances.FDOPA was prepared by electrophilic fluorination of the trimethylstannyl precursor with [ 18 F]F 2 , produced from [ 18 O] 2 via the double-shoot approach, leading to FDOPA with higher specific activity as compared to FDOPA which was synthesized, using [ 18 F]F 2 produced from 20 Ne, leading to FDOPA with a lower specific activity. The quality control of the product was performed using a validated UPLC system and compared with quality control with a conventional HPLC system. Impurities were identified using UPLC-MS. The [ 18 O] 2 double-shoot radionuclide production method yielded significantly more [ 18 F]F 2 with less carrier F 2 than the conventional method starting from 20 Ne. After adjustment of radiolabeling parameters substantially higher amounts of FDOPA with higher specific activity could be obtained. Quality control by UPLC was much faster and detected more side-products than HPLC. UPLC-MS showed that the most important side-product was FDOPA-quinone, rather than 6-hydroxydopa as suggested by the European Pharmacopoeia. The production and quality control of FDOPA were significantly improved by introducing the [ 18 O] 2 double-shoot radionuclide production method, and product analysis by UPLC, respectively. As a result, FDOPA is now routinely available for clinical practice and for distribution over distances.

Logistics for evaluation of doses received by IOE due to handling 18FDG-radiopharmaceutical during processing (IEN/CNEN) and in radiodiagnostic (clinical)

Energy Technology Data Exchange (ETDEWEB)

Santos, Osvaldir P. dos; Silva, Joao Carlos P.; Silva, Luiz Carlos Reina P.; Cortines, Geraldo, E-mail: osvaldir@ien.gov.br, E-mail: jcarlos@ien.gov.br, E-mail: reina@ien.gov.br, E-mail: gcortines@ien.gov.br [Instituto de Engenharia Nuclear (IEN/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

2013-07-01

The objective of this study is to propose an improvement in radiological practices involving production, transportation and application of radiopharmaceutical {sup 18}F, by tracking the radiation doses received by occupationally exposed individuals (OEI) that develop production practices, transportation and application of some patients in hospitals and clinics in Rio de Janeiro, the radiopharmaceutical {sup 18}FDG. In light of the results and observations of how these practices are developed, it's necessary to evaluate and suggest a logistics to minimize the doses received by OEI during these practices, seeking improvements in the actions and procedures for radiological protection. In practice the production of the radiopharmaceutical, the study focuses on the time of withdrawal of {sup 18}FDG cell processing, where the technician is exposed to higher dose rates. At this stage, we take to accomplish, yet two other reviews: the first is the placement of electronic dosimeters inside and outside the lead apron, whose objective is to assess the attenuation capacity of the apron. This last procedure refers to the use of a phantom cylindrical containing TLD 700 dosimeter in order to evaluate, using a mathematical model (MCNP), the doses ends (hand) of the technician, the process of removing the radiopharmaceutical of the cell and to compare the dosimetric dose recorded in the ring. Regarding the transport of {sup 18}FDG, we take into account the doses recorded in the cabin of the vehicle and the doses recorded in the dosimeter of the carrier. Finally, the doses received by health professionals who handle {sup 18}FDG are analyzed, since its withdrawal from the packing until administration to the patient. (author)

{sup 18}F-fluorocholine production at Center of Nuclear Technology Development, Brazil: synthesis and in vitro cytotoxicity studies; Producao de {sup 18}F-fluorocolina no Centro de Desenvolvimento da Tecnologia Nuclear: sintese e estudos de citotoxicidade in vitro

Energy Technology Data Exchange (ETDEWEB)

Costa, Flavia Mesquita

2014-07-01

{sup 18}F-fluorocholine ({sup 18}FCH) is promising biomarker for imaging of tumors using PET technology, being effective in the diagnosis of metastatic tumors and specific for the brain tumors, prostate, lung, among others. Despite already being used in some countries like France, Germany, Slovenia, Poland, Romania and Portugal, the {sup 18}FCH is not yet produced or marketed in Brazil. This work proposed the development of a new radiopharmaceutical based on choline labeled with {sup 18}F isotope for diagnostic PET imaging which is an increasing demand of the nuclear medicine national. It was also proposed the development of quality control assays in order to evaluate the radiopharmaceutical prior to its use in patients; in vitro test of toxicity in non-tumor cells (MRC-5), evaluating possible changes in cell proliferation caused by radiopharmaceutical impurities; and, to test the interaction's saturation of {sup 18}FCH with the tumor cells (PC-3 and U-87) and the competition with HC-3 and DMAE, performed to characterize the efficiency of the radiotracer uptake by tumor cells that express the choline transporter CHT. {sup 18}FCH was synthesized in two main steps, first by reaction with dibromomethane with fluoride-18, assisted by Kryptofix2.2.2, forming {sup 18}F-fluorobromomethane ({sup 18}FBrCH{sub 2}) and, then, the {sup 18}FBrCH{sub 2} reacted with the second precursor DMAE generating the final product, {sup 18}FCH. Synthesis duration was 45 minutes. {sup 18}FCH was obtained in 4.68 - 8.32% radiochemical yield, radiochemical purity greater than 99% and it was stable for up to 8 hours after production. The tested analytical methodologies were suitable for routine use in the quality control of {sup 18}FCH. The evaluation of the cytotoxic potential of impurities {sup 18}FCH, by clonogenic assay, showed that at the concentrations evaluated, the components do not alter the proliferative capacity of human healthy cells. The interaction of {sup 18}FCH with cell

First experience with early dynamic 18F-NaF-PET/CT in patients with chronic osteomyelitis

International Nuclear Information System (INIS)

Freesmeyer, M.; Stecker, F.F.; Schierz, J.-H.; Winkens, T.; Hofmann, G.O.

2014-01-01

This study investigates whether early dynamic positron emission tomography/computed tomography (ed-PET/CT) using 18 F-sodium fluoride-( 18 F-NaF) is feasible in depicting early phases of radiotracer distribution in patients with chronic osteomyelitis (COM). A total of 12 ed 18 F-NaF-PET/CT examinations were performed on 11 consecutive patients (2 female, 9 male; age 53 ± 12 years) in list mode over 5 min starting with radiopharmaceutical injection before standard late 18 F-NaF-PET/CT. Eight consecutive time intervals (frames) were reconstructed for each patient: four 15 s, then four 60 s. Several volumes of interest (VOI) were selected, representing the affected area as well as different reference areas within the bone and soft tissue. Maximum and mean ed standardized uptake values (edSUV max , edSUV mean , respectively) were calculated in each VOI during each frame to measure early fluoride influx and accumulation. Results were compared between affected and non-affected (contralateral) bones. Starting in the 31-45 s frame, the affected bone area showed significantly higher edSUV max and edSUV mean compared to the healthy contralateral region. The affected bone areas also significantly differed from non-affected contralateral regions in conventional late 18 F-NaF-PET/CT. This pilot study suggests that, in patients with COM, ed 18 F-NaF-PET offers additional information about early radiotracer distribution to standard 18 F-NaF-PET/CT, similar to a three-phase bone scan. The results should be validated in larger trials which directly compare ed 18 F-NaF-PET to a three-phase bone scan. (author)

Radionuclide production and radiopharmaceutical chemistry with BNL cyclotrons

International Nuclear Information System (INIS)

Lambrecht, R.M.; Wolf, A.P.

1985-01-01

The Brookhaven National Laboratory (BNL) radiopharmaceutical chemistry program focuses on production and utilization of radionuclides having a half-life of > 2 hr. However, a major portion of the BNL program is devoted to short-lived radionuclides, such as 11 C and 18 F. Activities encompassed in the program are classified into seven areas: cyclotron parameters, radiochemistry, design and rapid synthesis of radiopharmaceuticals and labeled compounds, radiotracer evaluation in animals, studies in humans, technology transfer, and several other areas

Routine production of 18F using 16.5 MeV cyclotron for synthesis of 2-(18F)fluro-2-deoxy-d-glucose (FDG)

International Nuclear Information System (INIS)

Abd Jalil Abd Hamid; Soni, P.S.; Rajan, M.G.R.

2006-01-01

A medium energy cyclotron with maximum of 75 mA beam current is capable of producing most common Positron Emission Tomography (PET) radionuclides in sufficient quantities. The cyclotron has two targets for production of Flourine-18. One is high yield target system (HYT) (1.2 mL) and the other is HYT Generation II (Gen-II) (2.2 mL) and capable of producing 110 and 170 GBq respectively. Enriched 18 O water (>95%) is used for the routine production of Flourine-18 using the 18 O(p,n) 18 F nuclear reaction and irradiated under helium gas pressurized at 59-65 kPa at a beam current of 35 mA - 55 mA for 20-67 minutes. The [ 18 F]fluoride ion produced are used for the synthesis of 2-fluoro-2-deoxy-D-glucose (2-[ 18 F]FDG). Various factors that may effect the production of PET radionuclides and one such factor includes the silver target body often introduce impurity such as silver oxides in form of black particles that can impede the (ID 0.75 mm) delivery line. Such contaminants would reduce the quantity of the available useful radioisotopes, and hinder the subsequent radiopharmaceutical processes. Used of HYT and HYT Gen-II for the routine production of 18 F- in few ten GBq quantities were reported

18F-fluorocholine production at Center of Nuclear Technology Development, Brazil: synthesis and in vitro cytotoxicity studies

International Nuclear Information System (INIS)

Costa, Flavia Mesquita

2014-01-01

18 F-fluorocholine ( 18 FCH) is promising biomarker for imaging of tumors using PET technology, being effective in the diagnosis of metastatic tumors and specific for the brain tumors, prostate, lung, among others. Despite already being used in some countries like France, Germany, Slovenia, Poland, Romania and Portugal, the 18 FCH is not yet produced or marketed in Brazil. This work proposed the development of a new radiopharmaceutical based on choline labeled with 18 F isotope for diagnostic PET imaging which is an increasing demand of the nuclear medicine national. It was also proposed the development of quality control assays in order to evaluate the radiopharmaceutical prior to its use in patients; in vitro test of toxicity in non-tumor cells (MRC-5), evaluating possible changes in cell proliferation caused by radiopharmaceutical impurities; and, to test the interaction's saturation of 18 FCH with the tumor cells (PC-3 and U-87) and the competition with HC-3 and DMAE, performed to characterize the efficiency of the radiotracer uptake by tumor cells that express the choline transporter CHT. 18 FCH was synthesized in two main steps, first by reaction with dibromomethane with fluoride-18, assisted by Kryptofix2.2.2, forming 18 F-fluorobromomethane ( 18 FBrCH 2 ) and, then, the 18 FBrCH 2 reacted with the second precursor DMAE generating the final product, 18 FCH. Synthesis duration was 45 minutes. 18 FCH was obtained in 4.68 - 8.32% radiochemical yield, radiochemical purity greater than 99% and it was stable for up to 8 hours after production. The tested analytical methodologies were suitable for routine use in the quality control of 18 FCH. The evaluation of the cytotoxic potential of impurities 18 FCH, by clonogenic assay, showed that at the concentrations evaluated, the components do not alter the proliferative capacity of human healthy cells. The interaction of 18 FCH with cell lines was saturable, with specific binding greater than 94%, attesting to the

The improved syntheses of 5-substituted 2'-[18F]fluoro-2'-deoxy-arabinofuranosyluracil derivatives ([18F]FAU, [18F]FEAU, [18F]FFAU, [18F]FCAU, [18F]FBAU and [18F]FIAU) using a multistep one-pot strategy

International Nuclear Information System (INIS)

Cai Hancheng; Li Zibo; Conti, Peter S.

2011-01-01

Introduction: We and others have previously reported a four-step radiosynthesis of a series of 2'-deoxy-2'-[ 18 F]fluoro-5-substituted-1-β-D-arabinofuranosyluracil derivatives including [ 18 F]FAU, [ 18 F]FEAU, [ 18 F]FFAU, [ 18 F]FCAU, [ 18 F]FBAU and [ 18 F]FIAU as thymidine derivatives for tumor proliferation and/or reporter gene expression imaging with positron emission tomography (PET). Although the radiosynthesis has been proven to be reproducible and efficient, this complicated multistep reaction is difficult to incorporate into an automated cGMP-compliant radiosynthesis module for routine production. Recently, we have developed a simple and efficient one-pot method for routine production of [ 18 F]FMAU. In this study, we studied the feasibility of radiosynthesizing [ 18 F]FAU, [ 18 F]FEAU, [ 18 F]FFAU, [ 18 F]FCAU, [ 18 F]FBAU and [ 18 F]FIAU using this newly developed method. Methods: Similar to the radiosynthesis of [ 18 F]FMAU, 5-substituted 2'-[ 18 F]fluoro-2'-deoxy-arabinofuranosyluracil derivatives ([ 18 F]FAU, [ 18 F]FEAU, [ 18 F]FFAU, [ 18 F]FCAU, [ 18 F]FBAU and [ 18 F]FIAU) were synthesized in one-pot radiosynthesis module in the presence of Friedel-Crafts catalyst TMSOTf and HMDS. Results: This one-pot radiosynthesis method could be used to produce [ 18 F]FAU, [ 18 F]FEAU, [ 18 F]FFAU, [ 18 F]FCAU, [ 18 F]FBAU and [ 18 F]FIAU. The overall radiochemical yields of these tracers varied from 4.1%±0.8% to 10.1%±1.9% (decay-corrected, n=4). The overall reaction time was reduced from 210 min to 150 min from the end of bombardment, and the radiochemical purity was >99%. Conclusions: The improved radiosyntheses of [ 18 F]FAU, [ 18 F]FEAU, [ 18 F]FFAU, [ 18 F]FCAU, [ 18 F]FBAU and [ 18 F]FIAU have been achieved with reasonable yields and high purity using a multistep one-pot method. The synthetic time has been reduced, and the reaction procedures have been significantly simplified. The success of this approach may make PET tracers [ 18 F]FAU, [ 18 F

Radiochemical stability of radiopharmaceutical preparations

International Nuclear Information System (INIS)

Martins, Patricia de A.; Silva, Jose L. da; Ramos, Marcelo P.S.; Oliveira, Ideli M. de; Felgueiras, Carlos F.; Herrerias, Rosana; Zapparoli Junior, Carlos L.; Mengatti, Jair; Fukumori, Neuza T.O.; Matsuda, Margareth M.N.

2011-01-01

The 'in vitro' stability studies of the radiopharmaceutical preparations are an essential requirement for routine practice in nuclear medicine and are an important parameter for evaluating the quality, safety and efficacy required for the sanitary registration of pharmaceutical products. Several countries have published guidelines for the evaluation of pharmaceutical stability. In Brazil, the stability studies should be conducted according to the Guide for Conducting Stability Studies published in the Resolution-RE n. 1, of 29th July 2005. There are also for radiopharmaceutical products, two specific resolutions: RDC-63 regulates the Good Manufacturing Practices for Radiopharmaceuticals and RDC-64 provides the Registration of Radiopharmaceuticals, both published on the 18th December 2009. The radiopharmaceutical stability is defined as the time during which the radioisotope can be safely used for the intended purpose. The radiochemical stability can be affected by a variety of factors, including storage temperature, amount of radioactivity, radioactive concentration, presence or absence of antioxidants or other stabilizing agents. The radiochemical stability studies must be established under controlled conditions determined by the effective use of the product. The aim of this work was to evaluate the radiochemical stability of labeled molecules with 131 I, 123 I, 153 Sm, 18 F, 51 Cr, 177 Lu and 111 In as well as 67 Ga and 201 Tl radiopharmaceuticals. Radiochemical purity was evaluated after production and in the validity period, with the maximum activity and in the recommended storage conditions. The analyses were carried out by thin-layer silica gel plate, paper chromatography and gel chromatography. The experimental results showed to be in accordance with the specified limits for all the analysed products. (author)

Research progress in radiolabeling imaging mechanism and clinical applications of "1"8F-FDG

International Nuclear Information System (INIS)

Zhai Shizhen; Yang Zhi; Du Jin

2011-01-01

PET/CT is one of the most advanced technologies contemporarily, achieving the combination of anatomical imaging and functional imaging. "1"8F-FDG is the most important positron radiopharmaceutical, which was used over 95% in total PET/CT imaging. FDG- PET has been extensively used in diagnosis of several kinds of diseases such as tumor, cardiac disease and epilepsy. The present review provides the history, the quality control, the imaging mechanisms as well as the research progress of the clinical applications of "1"8F-FDG. (authors)

Purification by ozonolysis of 18O enriched water after cyclotron irradiation and the utilization of the purified water for the production of [18F]-FDG (2-deoxy-2-[18F]-fluoro-D-glucose)

International Nuclear Information System (INIS)

Asti, M.; Grassi, E.; Sghedoni, R.; De Pietri, G.; Fioroni, F.; Versari, A.; Borasi, G.; Salvo, D.

2007-01-01

The high cost of virgin 18 O-enriched water has forced many researchers to study methods to purify and recycle enriched water after the first irradiation for the production of radiopharmaceuticals. In our study, [ 18 O]H 2 O was purified by ozonolysis and distillation. Analyses showed a large decrease in impurities after this treatment. The purification procedure was carried out after the production of 94 batches of [ 18 F]-FDG, which were manufactured using a GE Minitrace cyclotron and a GE Mx TracerLab synthesizer. Saturation yields after bombardment, using virgin and re-purified water were, respectively, 2864±204 MBq/μA and 2727±167 MBq/μA, a decrease of 5.5%. The decrease in [ 18 F]-FDG yield, from 67.2±0.7% to 65.5±0.9%, can be ascribed to the irradiation step only

Validation of the FDG (18F) radiochemical purity assay by thin layer chromatography; Validacao do ensaio de pureza radioquimica do FDG (18F) por cromatografia em camada delgada

Energy Technology Data Exchange (ETDEWEB)

Leao, R.L.C.; Oliveira, M.L.; Nascimento, J.E.; Nascimento, N.C.E.S., E-mail: renata.lleao@hotmail.com [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil). Div. de Producao de Radiofarmacos

2013-08-15

All methodologies utilized in radiopharmaceutical industry should be validated in order to prove that they meet the requirements of analytical applications, ensuring the reliability of the results. At a radiopharmaceutical industry there is one challenge aspect: sometimes it is not possible use a stable standard to perform the validation analysis. In order to overcome this difficulty, the objective of this study was to suggest a validation protocol for these methodologies, based on the recommendations of RE n° 899/Agencia Nacional de Vigilancia Sanitaria (ANVISA), and prove its efficiency, performing the radiochemical purity validation test of FDG (18F), by TLC. To obtain the calibration curve, we suggested that the theoretical activity values should be determined using a dose calibrator, simultaneously of each analysis performed by TLC, for 5 hours. The method was linear (R{sup 2} of 0.996), precise (CV% <5%) and accurate (96.85% < accuracy < 102.56%). In relation to the robustness test, our experiments evaluated the influence of the distance travelled by mobile phase, variations at mobile phase concentration and type of chromatographic plate (silica gel on glass or aluminium plates). The detection and quantification limits were determined (321.9 and 1065.6 kBq, respectively). As expected, this methodology was nonspecific, showing a slight spot corresponding to the FDM. The proposed protocol was efficient and the methodology tested was effective to determine the radiochemical purity of FDG (18F), in accordance to the limits recommended by ANVISA. (author)

In vivo biodistribution and pharmacokinetics of18F-labelled Spiegelmers: a new class of oligonucleotidic radiopharmaceuticals

International Nuclear Information System (INIS)

Boisgard, Raphael; Younes, Cheraz; Tavitian, Bertrand; Kuhnast, Bertrand; Hinnen, Francoise; Dolle, Frederic; Vonhoff, Stefan; Wlotzka, Britta; Klussmann, Sven; Verbavatz, Jean-Marc; Rousseau, Bernard; Fuerste, Jens Peter

2005-01-01

Single-stranded mirror-image oligonucleotides (Spiegelmers) are highly resistant to nuclease degradation and are capable of tightly and specifically binding to protein targets. Here we explored the potential of Spiegelmers as in vivo imaging probes for positron emission tomography (PET). We investigated the biodistribution and pharmacokinetics of [ 18 F]-l-DNA and [ 18 F]-l-RNA Spiegelmers by dynamic quantitative whole-body PET imaging after intravenous administration in non-human primates. Their metabolic profile was explored in primates and rats, and ex vivo autoradiography of [ 125 I]-l-RNA was performed in rat kidneys, the major organ for Spiegelmer uptake. Both [ 18 F]-l-DNA and [ 18 F]-l-RNA Spiegelmers were metabolically stable in plasma during 2 h after injection. No evidence of non-specific binding was found with either type of Spiegelmer in any tissue. The biodistribution and metabolic profiles of [ 18 F]-l-DNA and [ 18 F]-l-RNA Spiegelmers highlight their potential as radiotracers for in vivo imaging applications. (orig.)

Study of the production yields of {sup 18}F, {sup 11}C, {sup 13}N and {sup 15}O positron emitters from plasma-laser proton sources at ELI-Beamlines for labeling of PET radiopharmaceuticals

Energy Technology Data Exchange (ETDEWEB)

Amato, Ernesto [Section of Radiological Sciences, Department of Biomedical and Dental Sciences and of Morphologic and Functional Imaging, University of Messina (Italy); Italiano, Antonio, E-mail: italianoa@unime.it [Istituto Nazionale di Fisica Nucleare, Gruppo Collegato di Messina (Italy); Margarone, Daniele [Institute of Physics ASCR, v.v.i. (FZU), ELI-Beamlines Project, 182 21 Prague (Czech Republic); Pagano, Benedetta [Nuclear Medicine Unit, University Hospital “G. Martino”, Messina (Italy); Baldari, Sergio [Section of Radiological Sciences, Department of Biomedical and Dental Sciences and of Morphologic and Functional Imaging, University of Messina (Italy); Nuclear Medicine Unit, University Hospital “G. Martino”, Messina (Italy); Korn, Georg [Institute of Physics ASCR, v.v.i. (FZU), ELI-Beamlines Project, 182 21 Prague (Czech Republic)

2016-03-01

The development of novel compact PET radionuclide production systems is of great interest to promote the diffusion of PET diagnostics, especially in view of the continuous development of microfluidics labeling approaches. We studied the feasibility to produce clinically-relevant amounts of PET isotopes by means of laser-accelerated proton sources such that expected at the ELI-Beamlines facility. {sup 18}F, {sup 11}C, {sup 13}N and {sup 15}O production yields were calculated through the TALYS software, by taking into account the broad proton spectra expected. With the hypothesized proton fluencies, clinically-relevant amounts of radionuclides can be obtained, suitable to prepare single doses of {sup 18}F-, {sup 11}C- and {sup 13}N-labeled radiopharmaceuticals exploiting fast and efficient microfluidic labeling systems.

Study of the production yields of "1"8F, "1"1C, "1"3N and "1"5O positron emitters from plasma-laser proton sources at ELI-Beamlines for labeling of PET radiopharmaceuticals

International Nuclear Information System (INIS)

Amato, Ernesto; Italiano, Antonio; Margarone, Daniele; Pagano, Benedetta; Baldari, Sergio; Korn, Georg

2016-01-01

The development of novel compact PET radionuclide production systems is of great interest to promote the diffusion of PET diagnostics, especially in view of the continuous development of microfluidics labeling approaches. We studied the feasibility to produce clinically-relevant amounts of PET isotopes by means of laser-accelerated proton sources such that expected at the ELI-Beamlines facility. "1"8F, "1"1C, "1"3N and "1"5O production yields were calculated through the TALYS software, by taking into account the broad proton spectra expected. With the hypothesized proton fluencies, clinically-relevant amounts of radionuclides can be obtained, suitable to prepare single doses of "1"8F-, "1"1C- and "1"3N-labeled radiopharmaceuticals exploiting fast and efficient microfluidic labeling systems.

18F-Labelled catecholamine type radiopharmaceuticals in the diagnosis of neurodegenerative diseases and neuroendocrine tumours: approaches to synthesis and development prospects

Science.gov (United States)

Vatsadze, S. Z.; Eremina, O. E.; Veselova, I. A.; Kalmykov, S. N.; Nenajdenko, V. G.

2018-04-01

The pathogenesis of many socially significant diseases such as neurodegenerative dementias and neuroendocrine tumours involves imbalance of neurotransmitters. Among the known neuroimaging methods, positron emission tomography (PET) is the most perfect and informative technique for diagnosing these diseases. The potential of PET is largely determined by the inventory of available radiopharmaceuticals, that is, biologically active molecules containing short-lived nuclides with positron decay. This review gives a systematic account of the application of fluorine-18-labelled catecholamine type radiopharmaceuticals in clinical investigations of the sympathetic and central nervous systems. The methods for the synthesis of these agents and existing problems are considered. The material is arranged according to the mechanisms of reactions that underlie the synthetic approaches: electrophilic, nucleophilic and metal-catalyzed reactions. The bibliography includes 198 references.

Proposals for implementation of methodological aspects in the use of {sup 18}F-FDG in the Positron Emission Tomography; Propostas de implementações de aspectos metodológicos na utilização do {sup 18}F-FDG na Tomografia Por Emissão de Pósitron

Energy Technology Data Exchange (ETDEWEB)

Oliveira, Cássio Miri

2013-07-01

This work covered three objectives: to evaluate and implement methods for in vivo internal occupational monitoring of individuals involved during the {sup 18}F-FDG process production; to suggest a national Diagnostic Reference Level (DRL) for {sup 18}F-FDGPET oncologic procedures; and to obtain the 'Recovery Coefficients' (RCs) factors used to correct the radiopharmaceutical uptake in region of interest for a better quantification and evaluation of images. The methodology of internal monitoring was implemented in the radiopharmaceuticals production centers of Nuclear Technology Development Center (CDTN) in Belo Horizonte - MG and the Nuclear Science Regional Center, North-East (CRCN-NE) in Recife, PE, Brazil. The results demonstrated that the developed methodology was efficient to evaluate {sup 18}F-FDG incorporations in both centers; additionally, the methodology showed that there was possibility of {sup 18}F incorporation in the form of {sup 18}F-FDG during non-routine actions performed in the radiopharmaceutical production process. DRLs were suggested based on a questionnaire that was used for the survey of {sup 18}F-FDG administered activity in 72 Brazilian clinics currently licensed by the National Nuclear Energy Commission (CNEN). The results reported by 41 (57%) of the {sup 18}F-FDG-PET clinics showed variations up to 100% in the administered activities among clinics for the same procedure. The calculated DRL from the third quartile was 5.54 MBq/kg or 387.7 MBq (for a 70 kg standard patient). For image analysis, two phantoms were used for obtaining the RCs, the NEMA/IEC Body Phantom, which has spherical capture areas and the modified Jaszczak, which has cylindrical capitation capture areas. Both phantoms were tested for different lesion:BG activity ratios, in the amount of 4:1 and 10:1; for different acquisition time. RCs obtained according to NEMA and IEC standards were applied to the SUVmax and SUVmed semi quantification tools. Values of SUVmed

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.)

[18F]F15599, a novel 5-HT1A receptor agonist, as a radioligand for PET neuroimaging

International Nuclear Information System (INIS)

Lemoine, Laetitia; Verdurand, Mathieu; Vacher, Bernard; Blanc, Elodie; Newman-Tancredi, Adrian; Le Bars, Didier; Zimmer, Luc

2010-01-01

The serotonin-1A (5-HT 1A ) receptor is implicated in the pathophysiology of major neuropsychiatric disorders. Thus, the functional imaging of 5-HT 1A receptors by positron emission tomography (PET) may contribute to the understanding of its role in those pathologies and their therapeutics. These receptors exist in high- and low-affinity states and it is proposed that agonists bind preferentially to the high-affinity state of the receptor and therefore could provide a measure of the functional 5-HT 1A receptors. Since all clinical PET 5-HT 1A radiopharmaceuticals are antagonists, it is of great interest to develop a 18 F labelled agonist. F15599 (3-chloro-4-fluorophenyl-(4-fluoro-4{ [(5-methyl-pyrimidin-2-ylmethyl)-amino]-methyl}-piperidin-1-yl)-methanone) is a novel ligand with high affinity and selectivity for 5-HT 1A receptors and is currently tested as an antidepressant. In pharmacological tests in rat, it exhibits preferential agonist activity at post-synaptic 5-HT 1A receptors in cortical brain regions. Here, its nitro-precursor was synthesised and radiolabelled via a fluoronucleophilic substitution. Radiopharmacological evaluations included in vitro and ex vivo autoradiography in rat brain and PET scans on rats and cats. Results were compared with simultaneous studies using [ 18 F]MPPF, a validated 5-HT 1A antagonist radiopharmaceutical. The chemical and radiochemical purities of [ 18 F]F15599 were >98%. In vitro [ 18 F ]F15599 binding was consistent with the known 5-HT 1A receptors distribution (hippocampus, dorsal raphe nucleus, and notably cortical areas) and addition of Gpp(NH)p inhibited [ 18 F ]F15599 binding, consistent with a specific binding to G protein-coupled receptors. In vitro binding of [ 18 F]F15599 was blocked by WAY100635 and 8-OH-DPAT, respectively, prototypical 5-HT 1A antagonist and agonist. The ex vivo and in vivo studies demonstrated that the radiotracer readily entered the rat and the cat brain and generated few brain radioactive

[18F]F15599, a novel 5-HT1A receptor agonist, as a radioligand for PET neuroimaging.

Science.gov (United States)

Lemoine, Laëtitia; Verdurand, Mathieu; Vacher, Bernard; Blanc, Elodie; Le Bars, Didier; Newman-Tancredi, Adrian; Zimmer, Luc

2010-03-01

The serotonin-1A (5-HT(1A)) receptor is implicated in the pathophysiology of major neuropsychiatric disorders. Thus, the functional imaging of 5-HT(1A) receptors by positron emission tomography (PET) may contribute to the understanding of its role in those pathologies and their therapeutics. These receptors exist in high- and low-affinity states and it is proposed that agonists bind preferentially to the high-affinity state of the receptor and therefore could provide a measure of the functional 5-HT(1A) receptors. Since all clinical PET 5-HT(1A) radiopharmaceuticals are antagonists, it is of great interest to develop a( 18)F labelled agonist. F15599 (3-chloro-4-fluorophenyl-(4-fluoro-4{[(5-methyl-pyrimidin-2-ylmethyl)-amino]-methyl}-piperidin-1-yl)-methanone) is a novel ligand with high affinity and selectivity for 5-HT(1A) receptors and is currently tested as an antidepressant. In pharmacological tests in rat, it exhibits preferential agonist activity at post-synaptic 5-HT(1A) receptors in cortical brain regions. Here, its nitro-precursor was synthesised and radiolabelled via a fluoronucleophilic substitution. Radiopharmacological evaluations included in vitro and ex vivo autoradiography in rat brain and PET scans on rats and cats. Results were compared with simultaneous studies using [(18)F]MPPF, a validated 5-HT(1A) antagonist radiopharmaceutical. The chemical and radiochemical purities of [(18)F]F15599 were >98%. In vitro [(18)F]F15599 binding was consistent with the known 5-HT(1A) receptors distribution (hippocampus, dorsal raphe nucleus, and notably cortical areas) and addition of Gpp(NH)p inhibited [(18)F]F15599 binding, consistent with a specific binding to G protein-coupled receptors. In vitro binding of [(18)F]F15599 was blocked by WAY100635 and 8-OH-DPAT, respectively, prototypical 5-HT(1A) antagonist and agonist. The ex vivo and in vivo studies demonstrated that the radiotracer readily entered the rat and the cat brain and generated few brain

Developments in radioisotope production and labelling of radiopharmaceuticals

International Nuclear Information System (INIS)

Lambrecht, R.M.

1998-01-01

Recent developments in both reactor and accelerator production of radioisotopes finding applications in nuclear medicine and in biomedical research are summarised. The priorities for the production of 48 different cyclotron radioisotopes; and for 42 reactor produced radioisotopes finding biomedical applications are identified. Each includes 5 generator systems. The rapid expansion of cyclotron based radioisotope production and automated synthesis of short-lived radiopharmaceuticals with the position-emitting radionuclides continues to gain momentum. Recent feasibility studies of the cyclotron production of 186 Re, 99m Tc and of 99 Mo are cited as examples of motivation to develop accelerator alternatives to use of nuclear reactors for medical radioisotope production. Examples of SPET and PET radiopharmaceuticals labelled with 131 I, 123 I, 124 I, 18 F, and with therapeutic radionuclides are highlighted. (author)

An Unusual Case of Plasmablastic Lymphoma Presenting as Paravertebral Mass Evaluated by {sup 18}F-FDG PET/CT

Energy Technology Data Exchange (ETDEWEB)

Treglia, Giorgio; Paone, Gaetano; Stathis, Anastasios; Ceriani, Luca; Giovanella, Luca [Oncology Institute of Southern Switzerland, Bellinzona (Switzerland)

2014-03-15

A 60-year-old man underwent radiological investigations due to the onset of back pain. Computed tomography (CT) and magnetic resonance imaging (MRI) showed the presence of a paravertebral mass located ahead the body of the third thoracic vertebra. Based on these findings the patient underwent biopsy of the paravertebral mass, which showed the presence of a plasmablastic lymphoma. Therefore, the patient underwent fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography ({sup 18}F-FDG PET/CT) for staging. Before {sup 18}F-FDG injection, the patient had fasted for at least 6 h; at the time of the radiopharmaceutical injection he presented glucose blood levels corresponding to 98 mg/dl. Images were acquired 1 h after intravenous injection of 280 MBq of {sup 18}F-FDG according to the body mass index. PET images were interpreted visually and semiquantitatively by using the maximal standardized uptake value (SUVmax). {sup 18}F-FDG PET/CT showed moderate radiopharmaceutical uptake corresponding to the paravertebral lesion (SUVmax 3.3) and diffuse uptake in the skeleton suspicious for bone marrow neoplastic involvement, with more evident hypermetabolic areas in the left scapula (SUVmax 3.7), right sixth rib (SUVmax 3.5), and left iliac bone (SUVmax 3.4) (Fig. 1). Subsequent bone marrow biopsy confirmed the bone marrow infiltration by plasmablastic cells. Based on these findings, a final diagnosis of plasmablastic lymphoma with bone marrow involvement was performed and the patient was addressed to chemotherapy. Plasmablastic lymphoma is a rare CD20-negative large-cell lymphoma with plasmablastic features occurring primarily in HIV or Epstein-Barr virus positive individuals. Distinguishing this tumor from myeloma could be challenging. The most frequent site of presentation is the oral cavity, whereas extraoral localizations of plasmablastic lymphoma are considered to be very rare and they should be differentiated from extraosseous localization of

Long-circulating liposomes radiolabeled with [18F]fluorodipalmitin ([18F]FDP)

International Nuclear Information System (INIS)

Marik, Jan; Tartis, Michaelann S.; Zhang, Hua; Fung, Jennifer Y.; Kheirolomoom, Azadeh; Sutcliffe, Julie L.; Ferrara, Katherine W.

2007-01-01

Synthesis of a radiolabeled diglyceride, 3-[ 18 F]fluoro-1,2-dipalmitoylglycerol [[ 18 F]fluorodipalmitin ([ 18 F]FDP)], and its potential as a reagent for radiolabeling long-circulating liposomes were investigated. The incorporation of 18 F into the lipid molecule was accomplished by nucleophilic substitution of the p-toluenesulfonyl moiety with a decay-corrected yield of 43±10% (n=12). Radiolabeled, long-circulating polyethylene-glycol-coated liposomes were prepared using a mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, cholesterol, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N- [methoxy(polyethyleneglycol)-2000] ammonium salt (61:30:9) and [ 18 F]FDP with a decay-corrected yield of 70±8% (n=4). PET imaging and biodistribution studies were performed with free [ 18 F]FDP and liposome-incorporated [ 18 F]FDP. Freely injected [ 18 F]FDP had the highest uptake in the liver, spleen and lungs. Liposomal [ 18 F]FDP remained in blood circulation at near-constant levels for at least 90 min, with a peak concentration near 2.5%ID/cc. Since [ 18 F]FDP was incorporated into the phospholipid bilayer, it could potentially be used for radiolabeling a variety of lipid-based drug carriers

Quantitative analysis of 18F-NaF dynamic PET/CT cannot differentiate malignant from benign lesions in multiple myeloma.

Science.gov (United States)

Sachpekidis, Christos; Hillengass, Jens; Goldschmidt, Hartmut; Anwar, Hoda; Haberkorn, Uwe; Dimitrakopoulou-Strauss, Antonia

2017-01-01

A renewed interest has been recently developed for the highly sensitive bone-seeking radiopharmaceutical 18 F-NaF. Aim of the present study is to evaluate the potential utility of quantitative analysis of 18 F-NaF dynamic PET/CT data in differentiating malignant from benign degenerative lesions in multiple myeloma (MM). 80 MM patients underwent whole-body PET/CT and dynamic PET/CT scanning of the pelvis with 18 F-NaF. PET/CT data evaluation was based on visual (qualitative) assessment, semi-quantitative (SUV) calculations, and absolute quantitative estimations after application of a 2-tissue compartment model and a non-compartmental approach leading to the extraction of fractal dimension (FD). In total 263 MM lesions were demonstrated on 18 F-NaF PET/CT. Semi-quantitative and quantitative evaluations were performed for 25 MM lesions as well as for 25 benign, degenerative and traumatic lesions. Mean SUV average for MM lesions was 11.9 and mean SUV max was 23.2. Respectively, SUV average and SUV max for degenerative lesions were 13.5 and 20.2. Kinetic analysis of 18 F-NaF revealed the following mean values for MM lesions: K 1 = 0.248 (1/min), k 3 = 0.359 (1/min), influx (K i ) = 0.107 (1/min), FD = 1.382, while the respective values for degenerative lesions were: K 1 = 0.169 (1/min), k 3 = 0.422 (1/min), influx (K i ) = 0.095 (1/min), FD = 1. 411. No statistically significant differences between MM and benign degenerative disease regarding SUV average , SUV max , K 1 , k 3 and influx (K i ) were demonstrated. FD was significantly higher in degenerative than in malignant lesions. The present findings show that quantitative analysis of 18 F-NaF PET data cannot differentiate malignant from benign degenerative lesions in MM patients, supporting previously published results, which reflect the limited role of 18 F-NaF PET/CT in the diagnostic workup of MM.

Development of methodologies for internal exposure assessment due to the radiopharmaceutical 18FDG

International Nuclear Information System (INIS)

Lacerda, Isabelle Viviane Batista de

2013-01-01

The production of 18 F has increased in the last decade. It is produced basically for the synthesis of 18 F- fluorodeoxyglucose ( 18 FDG), the main radiopharmaceutical used in PET (Positron Emission Tomography) scans. The growth in the frequency of these tests resulted in rise of the number of occupationally exposed individuals (OEI) to the radionuclide 18 F as 18 FDG, increasing thereby the probability of its accidental incorporation. This study aimed to implement optimized techniques for assessing internal exposures of individuals occupationally exposed through both in vivo and in vitro bioassay methods during production and handling of 18 FDG at the Divisao de Producao de Radiofarmacos (DIPRA), Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN). The in vivo monitoring was conducted at the Laboratorio de Dosimetria Interna, Divisao de Laboratorios Tecnico-Cientificos (DILAB). For this bioassay method, measurements were done with a 3x3' NaI(Tl) scintillation detector coupled to Genie 2000 software. The calibration of the system was performed with a brain phantom containing a standard liquid source of 22 Na to simulate a contaminated individual. The calibration of the HPGe coaxial detector for in vitro monitoring was performed at the Laboratorio de Medidas de Atividade de Radionuclideos (DIPRA/CRCN-NE/CNEN) with a standard source of 22 Na. Base on the calibration factors, it was possible to determine the minimum detectable activities (MDA) for the systems by using direct measurements and simulation of uncontaminated urine. Then, through the biokinetic models published by ICRP 106 and edited by the AIDE software (version 6.0), it was possible to estimate the minimum detectable effective dose (MDED), which evaluates the detection sensitivity of the techniques developed. The MDED was estimated for in vivo and in vitro measurements performed 2.4 hours after the occurrence of incorporation by ingestion, since this is the period of higher retention fraction

Setting up an apparatus for routine preparation of [18F]FDG

International Nuclear Information System (INIS)

Fuechtner, F.; Steinbach, J.; Loesel, E.; Luecke, R.

1994-01-01

The most widely used radiopharmaceutical in positron emission tomography (PET) studies is 2-[ 18 F]fluoro-2-deoxy-D-glucose ([ 18 F]FDG). The [ 18 F]FDG-preparation device consists of two main parts, the processing unit, situated inside the hot cell and its control unit. A pump, the radiation monitors and a recorder are additionally used. All parts of the processing unit, such as the reaction vessel, purification columns, electro-magnetic and electric stream selection valves, fittings, tubes, a waste absorber, electrical and tube connectors, conductivity cells, radioactivity monitors (Geiger-Mueller tubes, 70034, VacuTec) and the manometer, are mounted on a stainless steel housing. The processing unit is remote controlled by the control unit via a common 24-wire cabel. The tubes for the target gas, the compressed N 2 (for delivering the liquids), and the vessels containing the liquids needed for the synthesis, are connected to the synthesis unit by PTFE tubing and luer adapters. (orig./EF)

Development of 18F-FDG ([F-18]-2-fluoro-2-deoxy-D-glucose) injection for imaging of tumor reflecting glucose metabolism. Results of preclinical studies

International Nuclear Information System (INIS)

Ino, Sento; Shimada, Takayuki; Kanagawa, Masaru; Suzuki, Noriaki; Kondo, Susumu; Shirakami, Yoshifumi; Ito, Osamu; Kato-Azuma, Makoto

1999-01-01

Fluorine-18-2-fluoro-2-deoxy-D-glucose ( 18 F-FDG) injection was prepared by a modification of a method originally developed by Hamacher et al. The dosage form is the injectable solution (2 ml) containing 185 MBq of 18 F-FDG at a calibration time. Preclinical studies of the agent were performed. Its radiochemical purity is more than 95% and expiration time is 4 hours after the calibration time at ambient temperature. No toxicity was observed with up to 200 mg/kg and 100 mg/kg of non-radioactive FDG intravenously injected to rats and dogs in single dose toxicity tests, respectively. Biodistribution studies demonstrated that the radioactivity was mainly distributed into brain (3.0 to 3.3% I.D./Organ at 30 minutes) and heart (4.2 to 5.8% I.D./Organ at 1 to 3 hours) after intravenous injection of the agent to normal rats. In a tumor transplanted mouse model (colon 26), tumor uptake was 10.9±3.5% I.D./g at 1 hr after intravenous injection of the agent, the radioactivity was retained until 3 hours. The radiation absorbed dose was estimated according to the MIRD Pamphlet based on the biodistribution data both in humans reported by Mejia et al. and rats described in this report. The radiation absorbed dose was not higher than those of commercially available radiopharmaceuticals. In conclusion, the 18 F-FDG injection is expected to be useful for further clinical application. (author)

Recent advances in radiopharmaceuticals

International Nuclear Information System (INIS)

Smith, S.

2000-01-01

Full text: Radiopharmaceuticals in Nuclear Medicine may be divided into diagnostic and therapeutic agents. The diagnostic area is perceived to be mature, while the therapeutic side of nuclear medicine is still evolving. There are over 100 diagnostic radiopharmaceutical products available, the greatest number applied in cardiology followed by oncology and neurology. The greatest success in therapeutic nuclear medicine has been achieved in thyroid cancer, hyperthyroidism and bone pain palliation. Those in the field believe the future of nuclear medicine resides in the growth potential of the emerging therapeutic market, hence much of the recent research has been focussed in the development of therapeutic agents for targeting cancers. Radiopharmaceuticals under development or in clinical trials involve the use of radionuclides such as Y-90, Pd-103, Ir-192, Re-188, I-131, Sm-153, Sn-114, Sr-90, Cu-64 and In-111. Advances in cyclotron and camera technology as well as automation has enhanced and widened the potential use of positron emitting radiopharmaceuticals such as F-18 Fluorodeoxyglucose (FDG). However the relationship between FDG uptake and glucose consumption in normal and diseased tissue is still to be defined. Many challenges remain for the nuclear medicine community to apply new knowledge of human biochemistry in the development of new radiopharmaceuticals. A better understanding of effects of radiation and its role in the design of therapeutic agents is undoubtedly pivotal for advancing therapeutic Nuclear Medicine into the future

Nucleophilic Fluorination Reactions in Novel Reaction Media for 18F-Fluorine Labeling Method

International Nuclear Information System (INIS)

Kim, Dong Wook; Jeong, Hwan Jeong; Lim, Seok Tae; Sohn, Myung Hee

2009-01-01

Noninvasive imaging of molecular and biological processes in living subjects with positron emission tomography (PET) provides exciting opportunities to monitor metabolism and detect diseases in humans. Measuring these processes with PET requires the preparation of specific molecular imaging probes labeled with 18F-fluorine. In this review we describe recent methods and novel trends for the introduction of 18 F-fluorine into molecules which in turn are intended to serve as imaging agents for PET study. Nucleophilic 18 F-fluorination of some halo- and mesyloxyalkanes to the corresponding 18 F-fluoroalkanes with 18 F-fluoride obtained from an 18 O(p,n) 18 F reaction, using novel reaction media system such as an ionic liquidor tert-alcohol, has been studied as a new method for 18 F-fluorine labeling. Ionic liquid method is rapid and particularly convenient because 18 F-fluoride in H 2 O can be added directly to the reaction media, obviating the careful drying that is typically required for currently used radiofluorination methods. The nonpolar protic tert-alcohol enhances the nucleophilicity of the fluoride ion dramatically in the absence of any kind of catalyst, greatly increasing the rate of the nucleophilic fluorination and reducing formation of byproducts compared with conventional methods using dipolar aprotic solvents. The great efficacy of this method is a particular advantage in labeling radiopharmaceuticals with 18 F-fluorine for PET imaging, and it is illustrated by the synthesis of 18 F-fluoride radiolabeled molecular imaging probes, such as 18 F-FDG, 18 F-FLT, 18 F-FP-CIT, and 18 F-FMISO, in high yield and purity and in shorter times compared to conventional syntheses

New radiosynthesis of 2-deoxy-2-[18F]fluoroacetamido-D-glucopyranose and its evaluation as a bacterial infections imaging agent

International Nuclear Information System (INIS)

Martinez, Miguel E.; Kiyono, Yasushi; Noriki, Sakon; Inai, Kunihiro; Mandap, Katheryn S.; Kobayashi, Masato; Mori, Tetsuya; Tokunaga, Yuji; Tiwari, Vijay N.; Okazawa, Hidehiko; Fujibayashi, Yasuhisa; Ido, Tatsuo

2011-01-01

Introduction: The diagnosis of infection and the ability to distinguish bacterial infection from nonbacterial inflammation by positron emission tomography (PET) have gained interest in recent years, but still few specific radiopharmaceuticals are available for use. In this study, we developed a new radiosynthesis method of 2-deoxy-2-[ 18 F]fluoroacetamido-D-glucopyranose ([ 18 F]FAG) by applying microwave irradiation and demonstrated that [ 18 F]FAG could be a potential radiopharmaceutical to distinguish bacterial infection from nonbacterial inflammation. Methods: 1,3,4,6-Tetra-O-acetyl-2-deoxy-2-bromoacetamido-D-glucopyranose was used as precursor, and labeling was performed under microwave irradiation conditions followed by alkaline hydrolysis and high-performance liquid chromatography (HPLC) purification. In vitro uptake of [ 18 F]FAG by Escherichia coli was performed. Tissue biodistribution of [ 18 F]FAG was performed in mice. Moreover, PET imaging acquisition of E. coli infection and nonbacterial inflammation models was performed in rats. Tissue radiotracer-accumulated sites were analyzed by hematoxylin and eosin staining and anti-E.coli immunostaining. Results: The radiosynthesis of [ 18 F]FAG was achieved with microwave irradiation, and the radiochemical yield was 9.7%±2.8% end of bombardment (EOB); the radiochemical purity was more than 98%, and the total synthesis time was 62 min. Compared with control group, in vitro uptake of [ 18 F]FAG by E. coli was significantly decrease in inhibition group (P 18 F]FAG from the animal body. [ 18 F]FAG clearly visualized the infection areas but not nonbacterial inflammation areas in PET studies. Quantitative analysis revealed that the uptake of [ 18 F]FAG into infection areas was significantly higher than that of [ 18 F]FAG into inflammation areas (P 18 F]FAG. Conclusions: Using 1,3,4,6-tetra-O-acetyl-2-deoxy-2-bromoacetamido-D-glucopyranose as a precursor, the new radiosynthesis method of [ 18 F]FAG was achieved in

Biologically stable [18F]-labeled benzylfluoride derivatives

International Nuclear Information System (INIS)

Magata, Yasuhiro; Lang, Lixin; Kiesewetter, Dale O.; Jagoda, Elaine M.; Channing, Michael A.; Eckelman, William C.

2000-01-01

Use of the [ 18 F]-fluoromethyl phenyl group is an attractive alternative to direct fluorination of phenyl groups because the fluorination of the methyl group takes place under milder reaction conditions. However, we have found that 4-FMeBWAY showed femur uptake equal to that of fluoride up to 30 min in rat whereas 4-FMeQNB had a significantly lower percent injected dose per gram in femur up to 120 min. For these and other benzylfluoride derivatives, there was no clear in vivo structure-defluorination relationship. Because benzylchlorides (BzCls) are known alkylating agents, benzylfluorides may be alkylating agents as well, which may be the mechanism of defluorination. On this basis, the effects of substitution on chemical stability were evaluated by the 4-(4-nitro-benzyl)-pyridine (NBP) test, which is used to estimate alkylating activity with NBP. The effect of substitution on the alkylating activity was evaluated for nine BzCl derivatives: BzCl; 3- or 4-methoxy (electron donation) substituted BzCl; 2-, 3-, or 4-nitro (electron withdrawing) substituted BzCl; and 2-, 3-, or 4-chloro (electron withdrawing) substituted BzCl. Taken together, the alkylating reactivity of 3-chloro-BzCl was the weakest. This result was then applied to [ 18 F]-benzylfluoride derivatives and in vivo and in vitro stability were evaluated. Consequently, 3-chloro-[ 18 F]-benzylfluoride showed a 70-80% decrease of defluorination in both experiments in comparison with [ 18 F]-benzylfluoride, as expected. Moreover, a good linear relationship between in vivo femur uptake and in vitro hepatocyte metabolism was observed with seven 18 F-labeled radiopharmaceuticals, which were benzylfluorides, alkylfluorides, and arylfluorides. Apparently, the [ 18 F]-fluoride ion is released by metabolism in the liver in vivo. In conclusion, 3-chloro substituted BzCls are the most stable, which suggests that 3-chloro benzylfluorides will be the most chemically stable compound. This result should be important in

Validation of the FDG (18F) radiochemical purity assay by thin layer chromatography

International Nuclear Information System (INIS)

Leao, R.L.C.; Oliveira, M.L.; Nascimento, J.E.; Nascimento, N.C.E.S.

2013-01-01

All methodologies utilized in radiopharmaceutical industry should be validated in order to prove that they meet the requirements of analytical applications, ensuring the reliability of the results. At a radiopharmaceutical industry there is one challenge aspect: sometimes it is not possible use a stable standard to perform the validation analysis. In order to overcome this difficulty, the objective of this study was to suggest a validation protocol for these methodologies, based on the recommendations of RE n° 899/Agencia Nacional de Vigilancia Sanitaria (ANVISA), and prove its efficiency, performing the radiochemical purity validation test of FDG (18F), by TLC. To obtain the calibration curve, we suggested that the theoretical activity values should be determined using a dose calibrator, simultaneously of each analysis performed by TLC, for 5 hours. The method was linear (R 2 of 0.996), precise (CV% <5%) and accurate (96.85% < accuracy < 102.56%). In relation to the robustness test, our experiments evaluated the influence of the distance travelled by mobile phase, variations at mobile phase concentration and type of chromatographic plate (silica gel on glass or aluminium plates). The detection and quantification limits were determined (321.9 and 1065.6 kBq, respectively). As expected, this methodology was nonspecific, showing a slight spot corresponding to the FDM. The proposed protocol was efficient and the methodology tested was effective to determine the radiochemical purity of FDG (18F), in accordance to the limits recommended by ANVISA. (author)

Distribution of 18F-5-fluorouracil in tumor-bearing mice and rats

International Nuclear Information System (INIS)

Shani, J.; Wolf, W.; Schlesinger, T.

1978-01-01

Extensive distribution studies of 18 F-5-fluorouracil ( 18 F-5-FU) in control and tumor-bearing mice (seven lines) and rats (eight lines) that have been shown or suspected to be responsive to 5-FU treatment were investigated with 18 F-5-FU. Studies were performed as a function of time, loading dose of 5-FU, and after a pretreatment regimen of 5-FU. Following the parenteral administration of 18 F-5-FU to tumor-bearing mice and rats there was slight preferential uptake by some of the tumor types, particularly subcutaneous leukemic tumors and breast adenocarcinomas. The degree of concentration in tumor tissue in comparison with surrounding tissues (blood, Muscle) was not such as to consider the radiopharmaceutical suitable for tumor localization. However, sufficient amounts of radioactivity localized in some tumors so that it might be possible to determine if a correlation exists between tumor uptake and anti-tumor effect of 5-fluorouracil. Another possible area of use might be in regulating the method of administration of the chemotherapeutic agent. (author)

Current status of PET imaging of neuroendocrine tumours ([18F]FDOPA, [68Ga]traces, [11C/[18F]-HTP)

International Nuclear Information System (INIS)

Ambrosini, A.; Morgini, J.J.; Nanni, C.; Castellucci, P.; Fanti, S.

2015-01-01

Neuroendocrine neoplasms (NEN) functional imaging is an evolving field that witnessed major advances in the past two decades. The routine use of PET/CT with an array of new radiotracers to specifically study NEN resulted in an increase in lesions detection. Currently, PET radiopharmaceuticals for NEN imaging include both metabolic ([18F]DOPA, [18F]FDG, [11C]/[18F]-HTP) and receptor-mediated compounds ([68Ga]DOTA-peptides). Discussion is still on-going regarding the clinical setting that may benefit the most from the use of one tracer over the other. [68Ga]DOTA-peptides are accurate for the detection of well differentiated NEN and are increasingly employed. Moreover, providing data on somatostatin receptors expression on NEN cells, they represent a fundamental procedure to be performed before starting therapy, as well as to guide treatment, with either hot or cold somatostatin analogues. The easy and economic synthesis process also favours their clinical employment even in centres without an on-site cyclotron. [18F]DOPA is accurate for studying well differentiated tumours however the difficult and expensive synthesis have limited its clinical employment. It currently can be successfully used for imaging tumours with variable to low expression of SSR (medullary thyroid carcinoma, neuroblastoma, pheocromocytoma), that cannot be accurately studied with [68Ga]DOTA-peptides. [11C]/[18F]-HTP has also been proposed to image well differentiated NEN, on the basis of serotonin pathway activity, for which [11C]/[18F]-HTP can be used as precursor. However, although preliminary data are encouraging, the feasibility of its widespread clinical use is still under discussion, mainly limited by a complex synthesis process and more proven advantages over other currently employed compounds. This review aims to provide an overview of the current status and clinical application of PET tracers to image well differentiated NEN and to focus on the still open-issues of debate

Consequences of radiopharmaceutical extravasation and therapeutic interventions: a systematic review

Energy Technology Data Exchange (ETDEWEB)

Pol, Jochem van der; Voeoe, Stefan [Maastricht University Medical Centre (MUMC+), Department of Radiology and Nuclear Medicine, Postbox 5800, Maastricht (Netherlands); Bucerius, Jan; Mottaghy, Felix M. [Maastricht University Medical Centre (MUMC+), Department of Radiology and Nuclear Medicine, Postbox 5800, Maastricht (Netherlands); University Hospital, RWTH Aachen University, Department of Nuclear Medicine, Aachen (Germany)

2017-07-15

Radiopharmaceutical extravasation can potentially lead to severe soft tissue damage, but little is known about incidence, medical consequences, possible interventions, and effectiveness of these. The aims of this study are to estimate the incidence of extravasation of diagnostic and therapeutic radiopharmaceuticals, to evaluate medical consequences, and to evaluate medical treatment applied subsequently to those incidents. A sensitive and elaborate literature search was performed in Embase and PubMed using the keywords ''misadministration'', ''extravasation'', ''paravascular infiltration'', combined with ''tracer'', ''radionuclide'', ''radiopharmaceutical'', and a list of keywords referring to clinically used tracers (i.e. ''Technetium-99m'', ''Yttrium-90''). Reported data on radiopharmaceutical extravasation and applied interventions was extracted and summarised. Thirty-seven publications reported 3016 cases of diagnostic radiopharmaceutical extravasation, of which three cases reported symptoms after extravasation. Eight publications reported 10 cases of therapeutic tracer extravasation. The most severe symptom was ulceration. Thirty-four different intervention and prevention strategies were performed or proposed in literature. Extravasation of diagnostic radiopharmaceuticals is common. {sup 99m}Tc, {sup 123}I, {sup 18}F, and {sup 68}Ga labelled tracers do not require specific intervention. Extravasation of therapeutic radiopharmaceuticals can give severe soft tissue lesions. Although not evidence based, surgical intervention should be considered. Furthermore, dispersive intervention, dosimetry and follow up is advised. Pharmaceutical intervention has no place yet in the immediate care of radiopharmaceutical extravasation. (orig.)

Influence of P-Glycoprotein Inhibition or Deficiency at the Blood-Brain Barrier on (18)F-2-Fluoro-2-Deoxy-D-glucose ( (18)F-FDG) Brain Kinetics.

Science.gov (United States)

Tournier, Nicolas; Saba, Wadad; Goutal, Sébastien; Gervais, Philippe; Valette, Héric; Scherrmann, Jean-Michel; Bottlaender, Michel; Cisternino, Salvatore

2015-05-01

The fluorinated D-glucose analog (18)F-2-fluoro-2-deoxy-D-glucose ((18)F-FDG) is the most prevalent radiopharmaceutical for positron emission tomography (PET) imaging. P-Glycoprotein's (P-gp, MDR1, and ABCB1) function in various cancer cell lines and tumors was shown to impact (18)F-FDG incorporation, suggesting that P-gp function at the blood-brain barrier may also modulate (18)F-FDG brain kinetics. We tested the influence of P-gp inhibition using the cyclosporine analog valspodar (PSC833; 5 μM) on the uptake of (18)F-FDG in standardized human P-gp-overexpressing cells (MDCKII-MDR1). Consequences for (18)F-FDG brain kinetics were then assessed using (i) (18)F-FDG PET imaging and suitable kinetic modelling in baboons without or with P-gp inhibition by intravenous cyclosporine infusion (15 mg kg(-1) h(-1)) and (ii) in situ brain perfusion in wild-type and P-gp/Bcrp (breast cancer resistance protein) knockout mice and controlled D-glucose exposure to the brain. In vitro, the time course of (18)F-FDG uptake in MDR1 cells was influenced by the presence of valspodar in the absence of D-glucose but not in the presence of high D-glucose concentration. PET analysis revealed that P-gp inhibition had no significant impact on estimated brain kinetics parameters K 1, k 2, k 3, V T , and CMRGlc. The lack of P-gp effect on in vivo (18)F-FDG brain distribution was confirmed in P-gp/Bcrp-deficient mice. P-gp inhibition indirectly modulates (18)F-FDG uptake into P-gp-overexpressing cells, possibly through differences in the energetic cell level state. (18)F-FDG is not a P-gp substrate at the BBB and (18)F-FDG brain kinetics as well as estimated brain glucose metabolism are influenced by neither P-gp inhibition nor P-gp/Bcrp deficiencies in baboon and mice, respectively.

Development of {sup 18}F-FDG ([F-18]-2-fluoro-2-deoxy-D-glucose) injection for imaging of tumor reflecting glucose metabolism. Results of preclinical studies

Energy Technology Data Exchange (ETDEWEB)

Ino, Sento; Shimada, Takayuki; Kanagawa, Masaru; Suzuki, Noriaki; Kondo, Susumu; Shirakami, Yoshifumi; Ito, Osamu; Kato-Azuma, Makoto [Nihon Medi-Physics Co., Ltd., Sodegaura, Chiba (Japan). Research Center

1999-07-01

Fluorine-18-2-fluoro-2-deoxy-D-glucose ({sup 18}F-FDG) injection was prepared by a modification of a method originally developed by Hamacher et al. The dosage form is the injectable solution (2 ml) containing 185 MBq of {sup 18}F-FDG at a calibration time. Preclinical studies of the agent were performed. Its radiochemical purity is more than 95% and expiration time is 4 hours after the calibration time at ambient temperature. No toxicity was observed with up to 200 mg/kg and 100 mg/kg of non-radioactive FDG intravenously injected to rats and dogs in single dose toxicity tests, respectively. Biodistribution studies demonstrated that the radioactivity was mainly distributed into brain (3.0 to 3.3% I.D./Organ at 30 minutes) and heart (4.2 to 5.8% I.D./Organ at 1 to 3 hours) after intravenous injection of the agent to normal rats. In a tumor transplanted mouse model (colon 26), tumor uptake was 10.9{+-}3.5% I.D./g at 1 hr after intravenous injection of the agent, the radioactivity was retained until 3 hours. The radiation absorbed dose was estimated according to the MIRD Pamphlet based on the biodistribution data both in humans reported by Mejia et al. and rats described in this report. The radiation absorbed dose was not higher than those of commercially available radiopharmaceuticals. In conclusion, the {sup 18}F-FDG injection is expected to be useful for further clinical application. (author)

Increasing feasibility and utility of 18F-FDOPA PET for the management of glioma

International Nuclear Information System (INIS)

Bell, Christopher; Dowson, Nicholas; Puttick, Simon; Gal, Yaniv; Thomas, Paul; Fay, Mike; Smith, Jye; Rose, Stephen

2015-01-01

Introduction: Despite radical treatment therapies, glioma continues to carry with it a uniformly poor prognosis. Patients diagnosed with WHO Grade IV glioma (glioblastomas; GBM) generally succumb within two years, even those with WHO Grade III anaplastic gliomas and WHO Grade II gliomas carry prognoses of 2–5 and 2 years, respectively. PET imaging with 18 F-FDOPA allows in vivo assessment of the metabolism of glioma relative to surrounding tissues. The high sensitivity of 18 F-DOPA imaging grants utility for a number of clinical applications. Methods: A collection of published work about 18 F-FDOPA PET was made and a critical review was discussed and written. Results: A number of research papers have been published demonstrating that in conjunction with MRI, 18 F-FDOPA PET provides greater sensitivity and specificity than these modalities in detection, grading, prognosis and validation of treatment success in both primary and recurrent gliomas. In further comparisons with 11 C-MET, 18 F-FLT, 18 F-FET and MRI, 18 F-FDOPA has shown similar or better efficacy. Recently synthesis cassettes have become available, making 18 F-FDOPA more accessible. Conclusions: According to the available data, 18 F-FDOPA PET is a viable radiotracer for imaging and treatment planning of gliomas. Advances in knowledge and implication for patient care: 18 F-FDOPA PET appears to be a viable radiopharmaceutical for the diagnosis and treatment planning of gliomas cases, improving on that of MRI and 18 F-FDG PET

Development of an HPLC method for the radiochemical purity evaluation of [18F]Fluoroestradiol

International Nuclear Information System (INIS)

Bispo, Ana Carolina de A.; Nascimento, Leonardo T.C. do; Costa, Flávia M.; Silva, Juliana B. da; Mamede, Marcelo

2017-01-01

18 F-Fluoroestradiol ([ 18 F]FES), an estrogen analog, is a radiopharmaceutical used in Positron Emission Tomography (PET) that allows evaluating the tumor cell receptor profile and the best therapy strategy, the staging, the prognosis and the response to therapy in several breast cancer cases. As there is not any pharmacopoeia's monograph of [ 18 F]FES to standardize its quality control criteria, this work presents a new HPCL's method to perform the [ 18 F]FES radiochemical purity. A liquid chromatograph was used with radioactivity and ultraviolet detectors. Three concentrations of fluoroestradiol standard solution were used along the test. Their retention time was compared to its relative radiolabelled analogue to confirm its identity. Several mobile phases with acetonitrile and two mobile phase flows were tested to optimize the runs. Peaks symmetry, retention time, theoretical plates and resolution were analyzed to choose the best conditions. The mean retention time of both standard Fluoroestradiol and [ 18 F]FES solutions were the same, demonstrating that [ 18 F]FES formulation did not interfere with [ 18 F]FES analysis. The best conditions were 1.2 mL/min and isocratic 40% V/V acetonitrile in water, which gave [ 18 F]FES peak resolution greater than 6 and symmetry factor of 1. Thus, the developed method is ready to be validated and implemented in [ 18 F]FES quality control routine in CDTN/Brazil. (author)

Preparation of 16α[18F] fluoro-17β-fluoroestradiol on domestic synthesis module

International Nuclear Information System (INIS)

Sun Chuanjin; Zhu Hong; Fang Keyuan

2012-01-01

To investigate the synthesis method of 16α-[ 18 F] fluoro-17β-fluoroestradiol on domestic synthesizing module, the automated synthesis was carried out through the reaction of 3-O-(methoxymethyl) -16,17-O-sulfuryl-16-epiestriol (MMSE, 1 mg) as precursor with 18 F- at 105 ℃ for 15 min in sealed system on domestic synthesizer, then 0.8 mL 1 mol/L HC1 dissolved in 7.2 mL acetonetrile was added in three parts to the reaction vessel for hydrolysis and hydrolysis reaction was performed at 105 ℃ for 6 min. The final reaction solution was purified by HPLC to give 18 F-FES. Preparation of 18 F-FES on domestic synthesis module was in the uncorrected synthesis yield of 8.2% (corrected synthesis yield 12.8%). Total synthesis time was about 70 min and radiochemical purity was higher than 98%. The product had good stability at room temperature. 18 F-FES injection can be prepared on domes- tic synthesis module and the quality can meet the requirements of radiopharmaceuticals for clinical use, (authors)

HPLC-MS technique for radiopharmaceuticals analysis and quality control

International Nuclear Information System (INIS)

Macasek, F.; Buriova, E.; Bruder, P.; Vera-Ruiz, H.

2003-01-01

Potentialities of liquid chromatography with mass spectrometric detector (MSD) were investigated with the objective of quality control of radiopharmaceuticals; 2-deoxy-2-[ 18 F]fluoro-D-glucose (FDG) being an example. Screening of suitable MSD analytical lines is presented. Mass-spectrometric monitoring of acetonitrile-aqueous ammonium formate eluant by negatively charged FDG.HCO 2 - ions enables isotope analysis (specific activity) of the radiopharmaceutical at m/z 227 and 226. Kryptofix 222 provides an intense MSD signal of the positive ion associated with NH 4 + at m/z 394. Expired FDG injection samples contain decomposition products from which at least one labelled by 18 F and characterised by signal of negative ions at m/z 207 does not correspond to FDG fragments but to C5 decomposition products. A glucose chromatographic peak, characterised by m/z 225 negative ion is accompanied by a tail of a component giving a signal of m/z 227, which can belong to [ 18 O]glucose; isobaric sorbitol signals were excluded but FDG-glucose association occurs in the co-elution of separation of model mixtures. The latter can actually lead to a convoluted chromatographic peak, but the absence of 18 F makes this inconsistent. Quantification and validation of the FDG component analysis is under way. (author)

Production and use of {sup 18}F by TRIGA nuclear reactor: a first report

Energy Technology Data Exchange (ETDEWEB)

Burgio, N.; Ciavola, C.; Festinesi, A.; Capannesi, G. [ENEA, Centro Ricerche Casaccia, Rome (Italy). Dipt. Innovazione

1999-02-01

The irradiation and radiochemical facilities at public research centre can contribute to the start up of the regional PET centre. In particular, the TRIGA reactor of Casaccia Research Centre could produce a sufficient amount of {sup 18}F to start up a PET centre and successively integrated the cyclotron production. This report establishes, in the light of the preliminary experimental works, a guideline to the reactor`s production and extraction of {sup 18}F in a convenient form for the synthesis of the most representative PET radiopharmaceutical: {sup 18}F-FDG. [Italiano] Le facilities di irraggiamento e i laboratori Radiochimici dei Centri Statali di Ricerca possono contribuire allo sviluppo di centri regionali PET (Tomografia ed Emissione Positronica). In particolare, il reattore TRIGA del Centro Ricerca Casaccia potrebbe produrre un quantitativo di {sup 18}F sufficiente alle attivita` formative propedeutiche al centro PET che, successivamente sarebbe in grado di avviare una propria produzione da ciclotrone. Questo rapporto stabilisce le linee guida sperimentali per la produzione del {sup 18}F da reattore nucleare e la sua successiva estrazione in una forma conveniente per la sintesi del piu` rappresentativo dei radiofarmaci PET: il {sup 18}F-FDG.

Load unload system optimization on H218O irradiation target used for 18F- production at the cyclotron cyclone 30 from IPEN-CNEN/SP

International Nuclear Information System (INIS)

Costa, Osvaldo Luiz da

2009-01-01

The demand growing in Brazil by the radiopharmaceutical [ 18 F]FDG in positron emission tomography (PET-CT) and the 109,7 minutes half life claim special attention to the productive chain of this radiopharmaceutical. Since the [ 18 O]water irradiation until the tomograph patient scanning, in sequential procedures that may spent about six hours, all the productive chain stages must be as reliable as possible, because any stage failed will be perceived in productive chain extremity. The position indication absence from Load and Unload 18 F- Target System valve in Cyclotron Accelerators Center resulted in 18 F- production loss, Irradiation Room contamination and the increase workers' dose responsible by operation and maintenance of irradiation systems. This study tested the behaviour of three types of position sensors (micro switch, reed switch and inductive sensor), into Irradiation Room 1.2 environment of the Cyclotron Accelerators Center, where there are high gamma radiation and neutrons rates because the routine 18 F- and 1 '2 3 I production, through this test was possible to discover the fitter position sensor to run on 18 F- Target, and after rewriting the programmable logic controller software was possible avoid this type of fail at 18 F- production time in Cyclotron Accelerators Center, and to grow up the reliability on [ 18 F]FDG productive chain. (author)

Performance of the RI exhaust filter at Chosun university cyclotron facility and {sup 18}F emission reduction

Energy Technology Data Exchange (ETDEWEB)

Jeong, Cheol Ki; Jang, Han; Lee, Goung Jin [Dept. of Nuclear Engineering, Chosun University, Gwangju (Korea, Republic of)

2017-03-15

Recently, the number of PET cyclotrons has increased in Korea. A cyclotron mainly produces {sup 18}F, which is used for the production of [{sup 18}F]FDG, a cancer diagnostic radiopharmaceutical. For radiation protection, the discharge control standard under the Nuclear Safety Act limits the radioactive concentration of {sup 18}F in the exhaust discharged from a nuclear power utilization facility to below 2,000 Bq m-3. However, the radioactive concentration of 18F discharged during [18F]FDG production at the cyclotron facility at Chosun University is maintained at about 1,500 Bq m{sup -3} on average, which is 75% of the concentration limit of the discharge control standard, and temporarily exceeds the standard as per the real-time monitoring results. This study evaluated the performance of the exhaust flter unit of the cyclotron facility at Chosun University by assessing the concentration of {sup 18}F in the exhaust, and an experiment was conducted on the discharge reduction, where {sup 18}F is discharged without reacting with the FDG precursors during [{sup 18}F]FDG synthesis and is immediately captured by the [{sup 18}F]FDG automatic synthesis unit. Based on the performance evaluation results of the exhaust flter at the cyclotron facility of Chosun University, the measured capture effciency before and after the flter was found to be 92%. Furthermore, the results of the discharge reduction experiment, where the exhaust {sup 18}F was immediately captured by the [{sup 18}F]FDG synthesizer, showed a very satisfactory 94.3% reduction in the concentration of discharge compared to the existing discharge concentration.

Automated synthesis with HPLC purification of 18F-FMISO as specific molecular imaging probe of tumor hypoxia

International Nuclear Information System (INIS)

Wang Mingwei; Zhang Yingjian; Zhang Yongping

2012-01-01

An improved automated synthesis of 1-H-1-(3-[ 18 F] fluoro-2-hydroxypropyl)-2-nitro-imidazole ( 18 F-FMISO), a specific molecular imaging probe of tumor hypoxia, was developed using an upgraded Explora GN module integrated with Explora LC for HPLC purification in this study. The radiochemical synthesis of 18 F-FMISO was started with precursor 1-( 2'-nitro-1'-imidazolyl)-2-O-tetrahydropyranyl-3-O-tosyl-propanediol (NITTP) and included nucleophilic [ 18 F] radio-fluorination at 120℃ for 5 min and hydrolysis at 130℃ for 8 min. The automated synthesis of 18 F-FMISO, presenting fast, reliable and multi-run features, could be completed with the total synthesis time of less than 65 min and radiochemical yield of 25%∼35% (without decay correction). The quality control of 18 F-FMISO was identical with the radiopharmaceutical requirements, especially the radiochemical purity of greater than 99% and high chemical purity and specific activity own to HPLC purification. (authors)

Labeling of complex molecules with 18F, 13N, and 11C

International Nuclear Information System (INIS)

Brownell, G.L.; Elmaleh, D.R.

1980-01-01

The overall objective during the period covered by this report was to develop a broad spectrum of radiopharmaceuticals labeled with short-lived cyclotron positron emitters, 11 C, 13 N and 18 F. The goals of the program during the last year were: (1) to complete the modular automated system for important precursor production - formaldehyde, methyliodide, cyanide; (2) to perform animal studies with the 18 F-glucose analogues 2FDG and 3FDG and measure the constants for both agents in different animals; and (3) to initiate the development of new fatty acid analogues for the myocardial imaging and metabolism. As part of a collaboration with other groups seeking new agents for myocardium and brain, 9-/sup 123m/Te-telluriumheptadecanoic acid as a myocardial imaging agent was studied. This compound could be used for designing new fatty acid analogues labeled with 11 C and 18 F that stay in the myocardium because of metabolic inhibition

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.

Radiopharmaceuticals in China. Current status and prospects

Energy Technology Data Exchange (ETDEWEB)

Jia, Hong-Mei; Liu, Bo-Li [Beijing Normal Univ. (China). Key Laboratory of Radiopharmaceuticals

2014-04-01

The review provides an overview of the current status of radiopharmaceuticals in China for in vivo clinical use and also describes some important advances in the past three decades. Development of the diagnostic and therapeutic radiopharmaceuticals as well as basic research on radiopharmaceutical chemistry are being introduced. The radiotracers developed in China include: (1) Brain perfusion imaging agents and CNS radiotracers for β-amyloid plaques, σ{sub 1} receptors, and dopamine D{sub 2} or D{sub 4} receptors; (2) {sup 99m}Tc- and {sup 18}F-labeled myocardial perfusion imaging agents; (3) tumor imaging agents including integrin-targeting radiotracer, novel sentinel lymph node imaging agents, hypoxia imaging agents, {sup 99m}Tc-labeled glucose derivatives, σ{sub 2} receptor imaging agents, folate receptor imaging agents, and potential radiotracers for imaging of human telomerase reverse transcriptase expression; (4) Potential infection imaging agents; (5) Potential asialoglycoprotein receptor imaging agents; (6) Other imaging agents. Moreover, some prospects of research and development of radiopharmaceuticals in the near future are discussed. (orig.)

{sup 11}C- and {sup 18}F Production at TPC RK2 Laboratory

Energy Technology Data Exchange (ETDEWEB)

Solin, O.; Johansson, S.; Eriksson, P-O.; Rajander, J.; Kokkomäki, E.; Helin, S.; Arponen, E.; Aromaa, J.; Savisto, N.; Bergman, J.; Heselius, S-J. [Turku PET Centre, Radiopharmaceutical Chemistry Laboratory and Accelerator Laboratory, Porthaninkatu 3, 20500 Turku (Finland)

2009-07-01

Four gas targets for production of [{sup 11}C]CO{sub 2} and [{sup 11}C]CH{sub 4} as well as static and one circulating water target for [{sup 18}F]fluoride production have been installed on the external beam line of the CC18/9 cyclotron (Efremov Institute for Electrophysical Apparatuses, St. Petersburg, Russia) at TPC. The cyclotron is capable of accelerating 18 MeV protons (9 MeV deuterons) at particle beam intensities in excess of 100 μA. The aim with these radionuclide production systems is high yield, high specific radioactivity precursor production for PET radiopharmaceuticals.

Positron emitting nuclides and their synthetic incorporation in radiopharmaceuticals

International Nuclear Information System (INIS)

Fowler, J.S.

1976-01-01

11 C, 13 N, and 15 O has potential applicability to the study of metabolism in humans. Problems in the synthesis of radiopharmaceuticals labeled with 11 C, 13 N, and 18 F are described: quality control, radiation exposure, carboxylic acids, glucose, amines, amino acids, nitrosources, fluoroethanol. 54 references

Radiopharmaceuticals for diagnosis. Final report

Energy Technology Data Exchange (ETDEWEB)

1994-03-01

In the period 1969-1986, this project was directed to the evolution of target-specific labeled chemicals useful for nuclear medical imaging, especially radioactive indicators suited to tracing adrenal functions and localizing tumors in the neuroendocrine system. Since 1986, this project research has focused on the chemistry of positron emission tomography (PET) ligands. This project has involved the evaluation of methods for radiochemical syntheses with fluorine-18, as well as the development and preliminary evaluation of new radiopharmaceuticals for positron emission tomography. In the radiochemistry area, the ability to predict fluorine-18 labeling yields for aromatic substitution reactions through the use of carbon-13 NMR analysis was studied. Radiochemical yields can be predicted for some structurally analogous aromatic compounds, but this correlation could not be generally applied to aromatic substrates for this reaction, particularly with changes in ring substituents or leaving groups. Importantly, certain aryl ring substituents, particularly methyl groups, appeared to have a negative effect on fluorination reactions. These observations are important in the future design of syntheses of complicated organic radiopharmaceuticals. In the radiopharmaceutical area, this project has supported the development of a new class of radiopharmaceuticals based on the monoamine vesicular uptake systems. The new radioligands, based on the tetrabenazine structure, offer a new approach to the quantification of monoaminergic neurons in the brain. Preliminary primate imaging studies support further development of these radioligands for PET studies in humans. If successful, such radiopharmaceuticals will find application in studies of the causes and treatment of neurodegenerative disorders such as Parkinson`s disease.

Load and unload system optimization on H218 O irradiation target used for 18F- production at the cyclotron cyclone 30 from IPEN-CNEN/SP, Brazil

International Nuclear Information System (INIS)

Costa, Osvaldo Luiz da

2009-01-01

The demand growing in Brazil by the radiopharmaceutical [ 18 F] FDG in positron emission tomography (PET-CT) and the 109,7 minutes half life claim special attention to the productive chain of this radiopharmaceutical. Since the [ 18 O]water irradiation until the tomograph patient scanning, in sequential procedures that may spent about six hours, all the productive chain stages must be as reliable as possible, because any stage failed will be perceived in productive chain extremity. The position indication absence from Load and Unload 18 F - Target System valve in Cyclotron Accelerators Center resulted in 18 F - production loss, Irradiation Room contamination and the increase workers dose responsible by operation and maintenance of irradiation systems. This study tested the behaviour of three types of position sensors (micro switch, reed switch and inductive sensor), into Irradiation Room 1.2 environment of the Cyclotron Accelerators Center, where there are high gamma radiation and neutrons rates because the routine 18 F - and 123 I production, through this test was possible to discover the fitter position sensor to run on 18 F - Target, and after rewriting the programmable logic controller software was possible avoid this type of fail at 18 F - production time in Cyclotron Accelerators Center, and to grow up the reliability on [ 18 F]FDG productive chain. (author)

Routinely automated production of 3'-deoxy-3'-[18F] fluorothymidine as a specific molecular imaging probe of tumor cell proliferation

International Nuclear Information System (INIS)

Wang Mingwei; Zhang Yingjian; Zhang Yongping

2011-01-01

This work was aimed at developing a routine for automated production of 3'-deoxy-3'-[ 18 F]fluorothymidine ( 18 F-FLT), a specific molecular imaging probe of tumor cell proliferation, using one-pot two-step strategy and an upgraded Explora GN module integrated with a semi-preparative HPLC system. Firstly, the nucleophilic [ 18 F] radiofluorination of precursor BDNT with activated 18 F ion was carried out at 120 degree C for 5 min to yield the labeled intermediate 18 F-BDFT. Secondly, the acidic hydrolysis of 18 F-BDFT was run at 110 degree C for 5 min to produce 18 F-FLT after addition of HCl, and 18 F-FLT was purified by HPLC. This automated production of 18 F-FLT is of fast, reliable and multi-run features, being completed within 65 min with radiochemical yield of 15%-25% (without decay correction). The quality control of 18 F-FLT was identical with the radiopharmaceutical requirements, especiallly the radiochemical purity of greater than 99% and high chemical purity and specific activity own to HPLC purification. (authors)

[{sup 18}F]F15599, a novel 5-HT{sub 1A} receptor agonist, as a radioligand for PET neuroimaging

Energy Technology Data Exchange (ETDEWEB)

Lemoine, Laetitia; Verdurand, Mathieu [Universite de Lyon, Laboratory of Neuropharmacology, Lyon (France); CERMEP - Imagerie du Vivant, PET Department, Lyon (France); Vacher, Bernard; Blanc, Elodie; Newman-Tancredi, Adrian [Centre de Recherches Pierre Fabre, Castres (France); Le Bars, Didier [CERMEP - Imagerie du Vivant, PET Department, Lyon (France); Zimmer, Luc [Universite de Lyon, Laboratory of Neuropharmacology, Lyon (France); CERMEP - Imagerie du Vivant, PET Department, Lyon (France); CERMEP - Imagerie du Vivant, ANIMAGE Department, Lyon (France)

2010-03-15

The serotonin-1A (5-HT{sub 1A}) receptor is implicated in the pathophysiology of major neuropsychiatric disorders. Thus, the functional imaging of 5-HT{sub 1A} receptors by positron emission tomography (PET) may contribute to the understanding of its role in those pathologies and their therapeutics. These receptors exist in high- and low-affinity states and it is proposed that agonists bind preferentially to the high-affinity state of the receptor and therefore could provide a measure of the functional 5-HT{sub 1A} receptors. Since all clinical PET 5-HT{sub 1A} radiopharmaceuticals are antagonists, it is of great interest to develop a{sup 18}F labelled agonist. F15599 (3-chloro-4-fluorophenyl-(4-fluoro-4{l_brace}[(5-methyl-pyrimidin-2-ylmethyl)-amino]-methyl{r_brace}-piperidin-1-yl)-methanone) is a novel ligand with high affinity and selectivity for 5-HT{sub 1A} receptors and is currently tested as an antidepressant. In pharmacological tests in rat, it exhibits preferential agonist activity at post-synaptic 5-HT{sub 1A} receptors in cortical brain regions. Here, its nitro-precursor was synthesised and radiolabelled via a fluoronucleophilic substitution. Radiopharmacological evaluations included in vitro and ex vivo autoradiography in rat brain and PET scans on rats and cats. Results were compared with simultaneous studies using [{sup 18}F]MPPF, a validated 5-HT{sub 1A} antagonist radiopharmaceutical. The chemical and radiochemical purities of [{sup 18}F]F15599 were >98%. In vitro [{sup 18}F ]F15599 binding was consistent with the known 5-HT{sub 1A} receptors distribution (hippocampus, dorsal raphe nucleus, and notably cortical areas) and addition of Gpp(NH)p inhibited [{sup 18}F ]F15599 binding, consistent with a specific binding to G protein-coupled receptors. In vitro binding of [{sup 18}F]F15599 was blocked by WAY100635 and 8-OH-DPAT, respectively, prototypical 5-HT{sub 1A} antagonist and agonist. The ex vivo and in vivo studies demonstrated that the radiotracer

Efficiency calibration of a HPGe detector for [18F] FDG activity measurements

International Nuclear Information System (INIS)

Fragoso, Maria da Conceicao de Farias; Lacerda, Isabelle Viviane Batista de; Albuquerque, Antonio Morais de Sa

2013-01-01

The radionuclide 18 F, in the form of flurodeoxyglucose (FDG), is the most used radiopharmaceutical for Positron Emission Tomography (PET). Due to [ 18 F]FDG increasing demand, it is important to ensure high quality activity measurements in the nuclear medicine practice. Therefore, standardized reference sources are necessary to calibrate of 18 F measuring systems. Usually, the activity measurements are performed in re-entrant ionization chambers, also known as radionuclide calibrators. Among the existing alternatives for the standardization of radioactive sources, the method known as gamma spectrometry is widely used for short-lived radionuclides, since it is essential to minimize source preparation time. The purpose of this work was to perform the standardization of the [ 18 F]FDG solution by gamma spectrometry. In addition, the reference sources calibrated by this method can be used to calibrate and test the radionuclide calibrators from the Divisao de Producao de Radiofarmacos (DIPRA) of the Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE). Standard sources of 152 Eu, 137 Cs and 68 Ge were used for the efficiency calibration of the spectrometer system. As a result, the efficiency curve as a function of energy was determined in wide energy range from 122 to 1408 keV. Reference sources obtained by this method can be used in [ 18 F]FDG activity measurements comparison programs for PET services localized in the Brazilian Northeast region. (author)

A report of the automated radiosynthesis of the tau positron emission tomography radiopharmaceutical, [18 F]-THK-5351.

Science.gov (United States)

Neelamegam, Ramesh; Yokell, Daniel L; Rice, Peter A; Furumoto, Shozo; Kudo, Yukitsuka; Okamura, Nobuyuki; El Fakhri, Georges

2017-02-01

The radiotracer, [ 18 F]-THK-5351, is a highly selective and high-binding affinity PET imaging agent for aggregates of hyper-phosphorylated tau protein. Our report is a simplified 1-pot, 2-step radiosynthesis of [ 18 F]-THK-5351. This report is broadly applicable for routine clinical production and multi-center trials on account of favorable half-life of flourine-18 and the use of a commercially available radiosynthesis module, the GE TRACERlab™ FX FN . First, the O-THP protected tosyl precursor underwent nucleophilic fluorinating reaction with potassium cryptand fluoride ([ 18 F] fluoride (K[ 18 F]/K 222 )) in Dimethyl sulfoxide at 110°C for 10 minutes followed by O-THP removal by using diluted hydrochloric acid (HCl) at same temperature. [ 18 F]-THK-5351 was purified via semi-preparative high-performance liquid chromatography and formulated by using 10% EtOH, United States Pharmacopeia (USP) in 0.9% sodium chloride for injection, USP and an uncorrected radiochemical yield of 21 ± 3.5%, with a specific activity of 153.11 ± 25.9 GBq/μmol (4138 ± 700 mCi/μmol) at the end of synthesis (63 minutes; n = 3). Copyright © 2016 John Wiley & Sons, Ltd.

18F-FDG positron autoradiography with a particle counting silicon pixel detector.

Science.gov (United States)

Russo, P; Lauria, A; Mettivier, G; Montesi, M C; Marotta, M; Aloj, L; Lastoria, S

2008-11-07

We report on tests of a room-temperature particle counting silicon pixel detector of the Medipix2 series as the detector unit of a positron autoradiography (AR) system, for samples labelled with (18)F-FDG radiopharmaceutical used in PET studies. The silicon detector (1.98 cm(2) sensitive area, 300 microm thick) has high intrinsic resolution (55 microm pitch) and works by counting all hits in a pixel above a certain energy threshold. The present work extends the detector characterization with (18)F-FDG of a previous paper. We analysed the system's linearity, dynamic range, sensitivity, background count rate, noise, and its imaging performance on biological samples. Tests have been performed in the laboratory with (18)F-FDG drops (37-37 000 Bq initial activity) and ex vivo in a rat injected with 88.8 MBq of (18)F-FDG. Particles interacting in the detector volume produced a hit in a cluster of pixels whose mean size was 4.3 pixels/event at 11 keV threshold and 2.2 pixels/event at 37 keV threshold. Results show a sensitivity for beta(+) of 0.377 cps Bq(-1), a dynamic range of at least five orders of magnitude and a lower detection limit of 0.0015 Bq mm(-2). Real-time (18)F-FDG positron AR images have been obtained in 500-1000 s exposure time of thin (10-20 microm) slices of a rat brain and compared with 20 h film autoradiography of adjacent slices. The analysis of the image contrast and signal-to-noise ratio in a rat brain slice indicated that Poisson noise-limited imaging can be approached in short (e.g. 100 s) exposures, with approximately 100 Bq slice activity, and that the silicon pixel detector produced a higher image quality than film-based AR.

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.)

Development of an HPLC method for the radiochemical purity evaluation of [{sup 18}F]Fluoroestradiol

Energy Technology Data Exchange (ETDEWEB)

Bispo, Ana Carolina de A.; Nascimento, Leonardo T.C. do; Costa, Flávia M.; Silva, Juliana B. da, E-mail: anacarollbispo@gmail.com [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Unidade de Pesquisa e Produção de Radiofármacos; Mamede, Marcelo, E-mail: mamede.mm@gmail.com [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento de Anatomia e Imagem

2017-07-01

{sup 18}F-Fluoroestradiol ([{sup 18}F]FES), an estrogen analog, is a radiopharmaceutical used in Positron Emission Tomography (PET) that allows evaluating the tumor cell receptor profile and the best therapy strategy, the staging, the prognosis and the response to therapy in several breast cancer cases. As there is not any pharmacopoeia's monograph of [{sup 18}F]FES to standardize its quality control criteria, this work presents a new HPCL's method to perform the [{sup 18}F]FES radiochemical purity. A liquid chromatograph was used with radioactivity and ultraviolet detectors. Three concentrations of fluoroestradiol standard solution were used along the test. Their retention time was compared to its relative radiolabelled analogue to confirm its identity. Several mobile phases with acetonitrile and two mobile phase flows were tested to optimize the runs. Peaks symmetry, retention time, theoretical plates and resolution were analyzed to choose the best conditions. The mean retention time of both standard Fluoroestradiol and [{sup 18}F]FES solutions were the same, demonstrating that [{sup 18}F]FES formulation did not interfere with [{sup 18}F]FES analysis. The best conditions were 1.2 mL/min and isocratic 40% V/V acetonitrile in water, which gave [{sup 18}F]FES peak resolution greater than 6 and symmetry factor of 1. Thus, the developed method is ready to be validated and implemented in [{sup 18}F]FES quality control routine in CDTN/Brazil. (author)

18F-labelling of oligonucleotides using succinimido 4-[18F]fluorobenzoat

International Nuclear Information System (INIS)

Hedberg, Elisabeth; Laangstroem, Bengt

1998-01-01

A general method for the labelling of oligodeoxynucleotide and oligonucleoside phosphorothioates in the 5'-position with the positron-emitting radionuclide 18 F (t 1/2 = 110 min) is described. The label was incorporated by the reaction of succinimido 4 -[ 18 F]fluorobenzoate 4 with oligonucleotides (18- and 20-mers) modified in the 5'-position with a hexylamine linker. Oligodeoxynucleotides 5'-GCT,AAG,CGA,TGC,CTC,CGT-3' (MTCa) and 5'-GAA,CCT,CTG,AGA,GTT,CAT,CT-3' (CROa) were labelled in 20±3 % (MTCa) and 13±3 % (CROa) radiochemical yields (non-isolated, decay-corrected and based on 4). Oligonucleoside phosphorotioates MTCa (S-MTCa) and CROa (S-CROa) were labelled in 9 and 7% isolated radiochemical yield, respectively (decay-corrected and based on 4). Labelled oligonucleotides and phosphorothioate analogues were separated from their unlabelled counterparts using reversed-phase perfusion chromatography. The molecular mass of a labelled oligonucleotide CROa was determined by ESI-MS after a mixed 18 F/ 19 F fluorobenzoate labelling experiment and corresponded with the expected structure. (au)

(18)F-labeled rhodamines as potential myocardial perfusion agents: comparison of pharmacokinetic properties of several rhodamines.

Science.gov (United States)

Bartholomä, Mark D; Zhang, Shaohui; Akurathi, Vamsidhar; Pacak, Christina A; Dunning, Patricia; Fahey, Frederic H; Cowan, Douglas B; Treves, S Ted; Packard, Alan B

2015-10-01

We recently reported the development of the [(18)F]fluorodiethylene glycol ester of rhodamine B as a potential positron emission tomography (PET) tracer for myocardial perfusion imaging (MPI). This compound was developed by optimizing the ester moiety on the rhodamine B core, and its pharmacokinetic properties were found to be superior to those of the prototype ethyl ester. The goal of the present study was to optimize the rhodamine core while retaining the fluorodiethyleneglycol ester prosthetic group. A series of different rhodamine cores (rhodamine 6G, rhodamine 101, and tetramethylrhodamine) were labeled with (18)F using the corresponding rhodamine lactones as the precursors and [(18)F]fluorodiethylene glycol ester as the prosthetic group. The compounds were purified by semipreparative HPLC, and their biodistribution was measured in rats. Additionally, the uptake of the compounds was evaluated in isolated rat cardiomyocytes. As was the case with the different prosthetic groups, we found that the rhodamine core has a significant effect on the in vitro and in vivo properties of this series of compounds. Of the rhodamines evaluated to date, the pharmacologic properties of the (18)F-labeled diethylene glycol ester of rhodamine 6G are superior to those of the (18)F-labeled diethylene glycol esters of rhodamine B, rhodamine 101, and tetramethylrhodamine. As with (18)F-labeled rhodamine B, [(18)F]rhodamine 6G was observed to localize in the mitochondria of isolated rat cardiomyocytes. Based on these results, the (18)F-labeled diethylene glycol ester of rhodamine 6G is the most promising potential PET MPI radiopharmaceutical of those that have evaluated to date, and we are now preparing to carry out first-in-human clinical studies with this compound. Copyright © 2015 Elsevier Inc. All rights reserved.

18F-labeled rhodamines as potential myocardial perfusion agents: comparison of pharmacokinetic properties of several rhodamines

International Nuclear Information System (INIS)

Bartholomä, Mark D.; Zhang, Shaohui; Akurathi, Vamsidhar; Pacak, Christina A.; Dunning, Patricia; Fahey, Frederic H.; Cowan, Douglas B.; Ted Treves, S.; Packard, Alan B.

2015-01-01

Introduction: We recently reported the development of the [ 18 F]fluorodiethylene glycol ester of rhodamine B as a potential positron emission tomography (PET) tracer for myocardial perfusion imaging (MPI). This compound was developed by optimizing the ester moiety on the rhodamine B core, and its pharmacokinetic properties were found to be superior to those of the prototype ethyl ester. The goal of the present study was to optimize the rhodamine core while retaining the fluorodiethyleneglycol ester prosthetic group. Methods: A series of different rhodamine cores (rhodamine 6G, rhodamine 101, and tetramethylrhodamine) were labeled with 18 F using the corresponding rhodamine lactones as the precursors and [ 18 F]fluorodiethylene glycol ester as the prosthetic group. The compounds were purified by semipreparative HPLC, and their biodistribution was measured in rats. Additionally, the uptake of the compounds was evaluated in isolated rat cardiomyocytes. Results: As was the case with the different prosthetic groups, we found that the rhodamine core has a significant effect on the in vitro and in vivo properties of this series of compounds. Of the rhodamines evaluated to date, the pharmacologic properties of the 18 F-labeled diethylene glycol ester of rhodamine 6G are superior to those of the 18 F-labeled diethylene glycol esters of rhodamine B, rhodamine 101, and tetramethylrhodamine. As with 18 F-labeled rhodamine B, [ 18 F]rhodamine 6G was observed to localize in the mitochondria of isolated rat cardiomyocytes. Conclusions: Based on these results, the 18 F-labeled diethylene glycol ester of rhodamine 6G is the most promising potential PET MPI radiopharmaceutical of those that have evaluated to date, and we are now preparing to carry out first-in-human clinical studies with this compound

18F-labeled Rhodamines as Potential Myocardial Perfusion Agents: Comparison of Pharmacokinetic Properties of Several Rhodamines

Science.gov (United States)

Bartholoma, Mark D.; Zhang, Shaohui; Akurathi, Vamsidhar; Pacak, Christina A.; Dunning, Patricia; Fahey, Frederic H.; Cowan, Douglas B.; Treves, S. Ted; Packard, Alan B.

2015-01-01

Introduction We recently reported the development of the [18F]fluorodiethylene glycol ester of rhodamine B as a potential positron emission tomography (PET) tracer for myocardial perfusion imaging (MPI). This compound was developed by optimizing the ester moiety on the rhodamine B core, and its pharmacokinetic properties were found to be superior to those of the prototype ethyl ester. The goal of the present study was to optimize the rhodamine core while retaining the fluorodiethyleneglycol ester prosthetic group. Methods A series of different rhodamine cores (rhodamine 6G, rhodamine 101, and tetramethylrhodamine) were labeled with 18F using the corresponding rhodamine lactones as the precursors and [18F]fluorodiethylene glycol ester as the prosthetic group. The compounds were purified by semipreparative HPLC, and their biodistribution was measured in rats. Additionally, the uptake of the compounds was evaluated in isolated rat cardiomyocytes. Results As was the case with the different prosthetic groups, we found that the rhodamine core has a significant effect on the in vitro and in vivo properties of this series of compounds. Of the rhodamines evaluated to date, the pharmacologic properties of the 18F-labeled diethylene glycol ester of rhodamine 6G are superior to those of the 18F-labeled diethylene glycol esters of rhodamine B, rhodamine 101, and tetramethylrhodamine. As with 18F-labeled rhodamine B, [18F]rhodamine 6G was observed to localize in the mitochondria of isolated rat cardiomyocytes. Conclusions Based on these results, the 18F-labeled diethylene glycol ester of rhodamine 6G is the most promising potential PET MPI radiopharmaceutical of those that have been evaluated to date, and we are now preparing to carry out first-in-human clinical studies with this compound. PMID:26205075

Permeability of gloves used in nuclear medicine departments to [(99m)Tc]-pertechnetate and [(18)F]-fluorodeoxyglucose: radiation protection considerations.

Science.gov (United States)

Ridone, S; Matheoud, R; Valzano, S; Di Martino, R; Vigna, L; Brambilla, M

2013-09-01

In order to evaluate the safety of the individual protection devices, the permeability of four different types of disposable gloves, commonly used in hospitals, was tested in relation to [(99m)Tc]-pertechnetate and to [(18)F]-fluorodeoxyglucose ([(18)F]-FDG). From these radiopharmaceutical solutions, a drop was deposited on the external surface of the glove which was opened and stretched with the external surface placed upward. The smear test technique permitted to evaluate the activity onto the inner surface of the glove at different times. The smear tests were measured in a well sodium iodide detector calibrated in efficiency for (99m)Tc and (18)F. The permeability was tested on ten samples of each type of gloves and was expressed as the ratio of the activity onto the inner surface at each time interval to the activity deposited on the external surface of the glove. For each type of gloves and for each sampling time, mean value, standard deviation and percentage coefficient of variation of permeability were evaluated. One type of gloves showed a low resistance to permeation of both radiopharmaceuticals, while another one only to pertechnetate. The other gloves were good performers. The results of this study suggest to test permeability for gloves used for handling radiopharmaceuticals, before their adoption in the clinical routine. This practice will provide a more careful service of radiation protection for nuclear medicine department staff. Copyright © 2013 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Recent progress in fluorine-18 labelled peptide radiopharmaceuticals

Energy Technology Data Exchange (ETDEWEB)

Okarvi, S.M. [Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Centre, Riyadh (Saudi Arabia)

2001-07-01

The application of biologically active peptides labelled with positron-emitting nuclides has emerged as a useful and interesting field in nuclear medicine. Small synthetic receptor-binding peptides are currently the preferred agents over proteins and antibodies for diagnostic imaging of various tumours. Due to the smaller size of peptides, both higher target-to-background ratios and rapid blood clearance can often be achieved with radiolabelled peptides. Hence, short-lived positron emission tomography (PET) isotopes are potential candidates for labelling peptides. Among a number of positron-emitting nuclides, fluorine-18 appears to be the best candidate for labelling bioactive peptides by virtue of its favourable physical and nuclear characteristics. The major disadvantage of labelling peptides with {sup 18}F is the laborious and time-consuming preparation of the {sup 18}F labelling agents. In recent years, various techniques have been developed which allow efficient labelling of peptides with {sup 18}F without affecting their receptor-binding properties. Moreover, the development of a variety of prosthetic groups has facilitated the efficient and site-specific labelling of peptides with {sup 18}F. The {sup 18}F-labelled peptides hold enormous clinical potential owing to their ability to quantitatively detect and characterise a wide variety of human diseases when using PET. Recently, a number of {sup 18}F-labelled bioactive peptides have shown great promise as diagnostic imaging agents. This review presents the recent developments in {sup 18}F-labelled biologically active peptides used in PET. (orig.)

Recent progress in fluorine-18 labelled peptide radiopharmaceuticals

International Nuclear Information System (INIS)

Okarvi, S.M.

2001-01-01

The application of biologically active peptides labelled with positron-emitting nuclides has emerged as a useful and interesting field in nuclear medicine. Small synthetic receptor-binding peptides are currently the preferred agents over proteins and antibodies for diagnostic imaging of various tumours. Due to the smaller size of peptides, both higher target-to-background ratios and rapid blood clearance can often be achieved with radiolabelled peptides. Hence, short-lived positron emission tomography (PET) isotopes are potential candidates for labelling peptides. Among a number of positron-emitting nuclides, fluorine-18 appears to be the best candidate for labelling bioactive peptides by virtue of its favourable physical and nuclear characteristics. The major disadvantage of labelling peptides with 18 F is the laborious and time-consuming preparation of the 18 F labelling agents. In recent years, various techniques have been developed which allow efficient labelling of peptides with 18 F without affecting their receptor-binding properties. Moreover, the development of a variety of prosthetic groups has facilitated the efficient and site-specific labelling of peptides with 18 F. The 18 F-labelled peptides hold enormous clinical potential owing to their ability to quantitatively detect and characterise a wide variety of human diseases when using PET. Recently, a number of 18 F-labelled bioactive peptides have shown great promise as diagnostic imaging agents. This review presents the recent developments in 18 F-labelled biologically active peptides used in PET. (orig.)

APPLICATION OF LIQUID-CHROMATOGRAPHY COMBINED WITH MASS-SPECTROMETRY (LC-MS) TO ESTABLISH IDENTITY AND PURITY OF PET-RADIOPHARMACEUTICALS

NARCIS (Netherlands)

FRANSSEN, EJF; LUURTSEMA, G; MEDEMA, J; VISSER, GM; JERONISMUSSHALINGH, CM; BRUINS, AP; VAALBURG, W

This article describes the application of liquid chromatography combined with mass-spectrometry (LC-MS) as a new quality control tool for PET-radiopharmaceuticals. The final step in the production of 2-[F-18]fluoro-2-deoxy-D-glucose (F-18-FDG) is a purification by HPLC. This procedure was validated

International symposium on trends in radiopharmaceuticals (ISTR-2005). Book of extended synopses

International Nuclear Information System (INIS)

2005-01-01

Radiopharmaceuticals, along with imaging instrumentation, are the pillars that support the edifice of clinical nuclear medicine and the former is the major driver enabling investigations of molecular phenomena for better understanding of human disease and developing effective treatments. The growth of nuclear medicine has been intimately linked to availability of new radioisotopes and the discovery of new radiopharmaceuticals. The field of radiopharmaceuticals has witnessed continuous evolution thanks to the immense contributions of scientists from diverse disciplines such as radiochemistry, inorganic chemistry, organic chemistry, biochemistry, physiology and pharmacology. Several milestones can be cited in the trajectory of this growth, which include continuing development of a plethora of 99 mTc radiopharmaceuticals, automated synthesis of 18 F labelled compounds, labelled peptides for accurate mapping of metastasis and the advances in radionuclide therapy. The International Symposium on Trends in Radiopharmaceuticals, ISTR-2005, under the auspices of International Atomic Energy Agency, will provide scientists and professionals working in the field of radiopharmaceuticals and related sciences an opportunity to review the exciting developments in the field. The International Atomic Energy Agency has been organizing such Symposia on Radiopharmaceuticals since 1973 and the last one was held in Lisbon, Portugal, in 1998

International symposium on trends in radiopharmaceuticals (ISTR-2005). Book of extended synopses

Energy Technology Data Exchange (ETDEWEB)

NONE

2005-07-01

Radiopharmaceuticals, along with imaging instrumentation, are the pillars that support the edifice of clinical nuclear medicine and the former is the major driver enabling investigations of molecular phenomena for better understanding of human disease and developing effective treatments. The growth of nuclear medicine has been intimately linked to availability of new radioisotopes and the discovery of new radiopharmaceuticals. The field of radiopharmaceuticals has witnessed continuous evolution thanks to the immense contributions of scientists from diverse disciplines such as radiochemistry, inorganic chemistry, organic chemistry, biochemistry, physiology and pharmacology. Several milestones can be cited in the trajectory of this growth, which include continuing development of a plethora of {sup 99}mTc radiopharmaceuticals, automated synthesis of {sup 18}F labelled compounds, labelled peptides for accurate mapping of metastasis and the advances in radionuclide therapy. The International Symposium on Trends in Radiopharmaceuticals, ISTR-2005, under the auspices of International Atomic Energy Agency, will provide scientists and professionals working in the field of radiopharmaceuticals and related sciences an opportunity to review the exciting developments in the field. The International Atomic Energy Agency has been organizing such Symposia on Radiopharmaceuticals since 1973 and the last one was held in Lisbon, Portugal, in 1998.

HPLC-MS technique for radiopharmaceuticals research and control

International Nuclear Information System (INIS)

Macasek, F.; Bruder, P.; Buriova, E.

2002-01-01

A liquid chromatography/refractive index detector/radiometric detector/ mass spectrometric detector combination (Agilent 1100 HPLC/RAD/DAD/RID/MSD system) is used as a complex technique for quality assessment of radiopharmaceuticals such as 2-deoxy-2-[ 18 F]fluoro-D-glucose (FDG). Optimisation of HPLC/MS analysis was performed investigating the electrospray ionisation (ESI) analytical signal of the mass spectrometer as a function of solvent composition. The anion-exchange eluents applied as specified by the pharmacopoeia are not suitable for ESI detection due to high ion concentrations. Therefore, solutions of glucose in methanol/water and acetonitrile/water solutions of various semi-volatile electrolytes (ammonium chloride, formic acid, ammonium formate) were analysed by flow injection analysis (FIA) and chromatographically. The best analytical response was obtained with acetonitrile : 0.25% ammonium formate = 80:20 solutions. The most intense MSD signals of FDG in ammonium formate were obtained for the following complex ions: (i) positive ions: fdg.NH 4 + , fdg.Na + and (fdg 2 -CH 3 O).Na + (m/z = 200, 205 and 344); (ii) negative ions: fdg.Cl - and fdg.HCOO - (m/z= 217 and 227). The HPLC-MS analysis with Zorbax C-18 and Asahipak-NH2P50 columns gave evidence of admixtures and radiolytic formation of deoxyglucose, deoxychloro-glucose, erythrose, erythritol, gluconic acid, lactose, raffinose, saccharic acid, sorbitol/[ 19 F]FDG, sorbitol/[ 19 F]FDG, xylitol, and other compounds. However, radiometric analysis of expired samples of [ 18 F]FDG gave evidence of a very high radiation stability of its water-ethanol solutions at the point of output of radioactive products. Remarkable is the exceedingly high complexity of the mass spectra of FDG as compared to glucose. Therefore, further research concerns the influence of sodium chloride, linearity of signal response, impurities (mannitol, mannose etc.) interference, and robustness of the MS analysis, with special attention

HPLC-MS technique for radiopharmaceuticals research and control

Energy Technology Data Exchange (ETDEWEB)

Macasek, F; Bruder, P [Department of Nuclear Chemistry, Faculty of Natural Sciences, Comenius University, Bratislava (Slovakia); Buriova, E [Cyclotron Centre of the Slovak Republic, Slovak Office of Standards, Metrology and Testing, Bratislava (Slovakia)

2002-03-01

A liquid chromatography/refractive index detector/radiometric detector/ mass spectrometric detector combination (Agilent 1100 HPLC/RAD/DAD/RID/MSD system) is used as a complex technique for quality assessment of radiopharmaceuticals such as 2-deoxy-2-[{sup 18}F]fluoro-D-glucose (FDG). Optimisation of HPLC/MS analysis was performed investigating the electrospray ionisation (ESI) analytical signal of the mass spectrometer as a function of solvent composition. The anion-exchange eluents applied as specified by the pharmacopoeia are not suitable for ESI detection due to high ion concentrations. Therefore, solutions of glucose in methanol/water and acetonitrile/water solutions of various semi-volatile electrolytes (ammonium chloride, formic acid, ammonium formate) were analysed by flow injection analysis (FIA) and chromatographically. The best analytical response was obtained with acetonitrile : 0.25% ammonium formate = 80:20 solutions. The most intense MSD signals of FDG in ammonium formate were obtained for the following complex ions: (i) positive ions: fdg.NH{sub 4}{sup +}, fdg.Na{sup +} and (fdg{sub 2}-CH{sub 3}O).Na{sup +} (m/z = 200, 205 and 344); (ii) negative ions: fdg.Cl{sup -} and fdg.HCOO{sup -} (m/z= 217 and 227). The HPLC-MS analysis with Zorbax C-18 and Asahipak-NH2P50 columns gave evidence of admixtures and radiolytic formation of deoxyglucose, deoxychloro-glucose, erythrose, erythritol, gluconic acid, lactose, raffinose, saccharic acid, sorbitol/[{sup 19}F]FDG, sorbitol/[{sup 19}F]FDG, xylitol, and other compounds. However, radiometric analysis of expired samples of [{sup 18}F]FDG gave evidence of a very high radiation stability of its water-ethanol solutions at the point of output of radioactive products. Remarkable is the exceedingly high complexity of the mass spectra of FDG as compared to glucose. Therefore, further research concerns the influence of sodium chloride, linearity of signal response, impurities (mannitol, mannose etc.) interference, and

Test and implementation of position sensors on load and unload [18O]H2O control valve of the target used in 18F - production by proton irradiation

International Nuclear Information System (INIS)

Costa, Osvaldo L. da; Sciani, Valdir

2009-01-01

The radionuclide 18 F used to produce the radiopharmaceutical [ 18 F]FDG has 109.7 min of half-life, becoming your productive chain so peculiar, because since the beginning of [ 18 O]H 2 O irradiation until the PET-CT exam there is a period about six hours, and any procedure fail in the productive chain will result in a delay to the PET CT exam. The absence of the position signs from [ 18 O]H 2 O load and unload valve of the target may result in 18 F production loss and even area contamination around the target. In this paper, three types of position sensors, into cyclotron radionuclides production environment in Cyclotron Accelerator Center from IPEN-CNEN/SP were tested. The tests were an indicative to discover the fitter sensor to the [ 18 O]H 2 O load and unload valve from target used in [ 18 F]fluoride production. After finding the fitter sensor, it was implemented in 18 F- target, supplying the correct position from [ 18 O]H 2 O load and unload valve to programmable logic controller, that had the software modified, respecting in this way the valve position. By this way, it was possible to reduce the incidence of fails, increasing the reliability in [ 18 F]FDG productive chain. (author)

Estimation of absorbed and effective dose in {sup 18}F-FDG em PET- CT exams for diagnosis of lung cancer; Estimativa de dose absorvida e efetiva em exames de {sup 18}F-FDG em PET- CT para diagnostico de cancer de pulmao

Energy Technology Data Exchange (ETDEWEB)

Carvalho, Guilherme Neto de Pinho; Santana, Priscila do Carmo, E-mail: guinpc1@ufmg.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Departamento de Anatomia e Imagem; Oliveira, Paulo Marcio Campos de; Reis, Lucas Paixao dos [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

2015-04-15

This paper presents an evaluation of tissues and organs absorbed doses as well as the effective dose resulting from PET-CT scans performed with {sup 18}F-FDG radiopharmaceutical for lung cancer diagnosis in whole body scans. The ICRP-106 biokinetic model was used to estimate the absorbed and effective doses from the radiopharmaceutical for both male and female patient according to the characteristics of anthropomorphic Alderson Rando® simulators. Computer Tomography doses were evaluated using thermoluminescent detectors inserted in the same anthropomorphic simulators. Optimization protocols for image acquisition and the use of automatic exposure control were used in order to reduce patient doses, taking into account the equipment model and its system. The effective dose in female patients was 5.8 mSv. The effective dose in male patients was 8.4 mSv. The dose values estimated for the {sup 18}F-FDG PET-CT scan are below the values described in the literature. This is because the CT was not used for diagnostic but for morphological mapping. (author)

Optimization of internal monitoring methodology of {sup 18}F in the form of {sup 18}FDG at the CRCN-NE, Recife, Pernambuco, Brazil; Otimizacao da metodologia de monitoracao interna de {sup 18}F na forma de {sup 18}FDG no CRCN-NE

Energy Technology Data Exchange (ETDEWEB)

Lacerda, Isabelle V.B.; Xavier, Aline C.S.; Lima, Fabiana F.; Oliveira, Mercia L., E-mail: fflima@cnen.gov.b, E-mail: mercial@cnen.gov.b, E-mail: falima@cnen.gov.b [Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN-PE), Recife, PE (Brazil); Oliveira, Cassio M., E-mail: cmo@cdtn.b [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil); Silva, Tania V. da; Alonso, Thessa C.; Silva, Teogenes A. da, E-mail: silvatv@cdtn.b, E-mail: alonso@cdtn.b, E-mail: silvata@cdtn.b [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN), Belo Horizonte, MG (Brazil)

2011-07-01

The work aims to optimize and improve the efficiency of the internal monitoring technique developed at Centro Regional de Ciencias Nucleares do Nordeste for F-18 in form of F-18DG radiopharmaceuticals. It was performed two assays for the methodology developed. The first was performed in a makeshift room, while the second was performed in a room with walls reinforced with concrete. The detection system was a NaI (Tl) 3{sup x} 3{sup s}cintillation detector, coupled with the software Genie 2000. In order to obtain the calibration factor, a brain phantom containing {sup 22}Na liquid source was measured. The interpretation of the bioassay data was performed using the biokinetic models provided by the ICRP 53 and edited by software AIDE-version 6, which gives the fraction of activity retained in the organs as a function of time. The sensitivities of detection were similar, resulting in a minimum detectable dose below 1 mSv, as recommended by the IAEA. (author)

A comparison of [/sup 18/F]spiroperidol, [/sup 18/F]benperidol and [/sup 18/F] haloperidol kinetics in baboon brain

International Nuclear Information System (INIS)

Arnett, C.D.; Shiue, C.Y.; Wolf, A.P.; Fowler, J.S.; Logan, J.

1984-01-01

Neuroleptic receptor ligands, spiroperidol, benperidol and haloperidol were labeled with fluorine-18 by a nucleophilic aromatic substitution reaction of p-nitrobenzo-nitrile with /sup 18/F/sup -/ to produce p-[/sup 18/F]fluorobenzonitrile which was converted to p-[/sup 18/F]fluoro-y-chlorobutyrophenone and then alkylated with the appropriate amine to give [/sup 18/F]spiroperidol ([/sup 18/F]SP), [/sup 18/F]benperidol ([/sup 18/F]BEN), or [/sup 18/F]haloperidol ([/sup 18/F]HAL). Specific activity ranged from 3 to 6 Ci/μmol. Anesthetized baboons were injected with 6-17 mCi of [/sup 18/F]-labeled tracer. Kinetic curves (striatum and cerebellum) were obtained from PETT scans up to 4 hr with each drug; [/sup 18/F]SP was studied to 8 hr. [/sup 18/F]SP and [/sup 18/F]BEN exhibited similar kinetics in striatum, with radioactivity concentration plateauing by 30 min after injection and remaining constant for the remainder of the study. These two compounds cleared rapidly from the cerebellum. [/sup 18/F]HAL showed a much different kinetic pattern in the striatum. Although it reached a higher striatal concentration (≅0.07% per ml vs. ≅ 0.02% per ml for [/sup 18/F]SP or [/sup 18/F]BEN), a peak occurred at 30 min after injection, followed by a decline almost as rapid as that in the cerebellum. Plasma analyses for [/sup 18/F]SP showed > 90% unchanged drug up to 5 min and ≅ 30% metabolites at 20 min after injection. Pretreatment with (+)-butaclamol abolished the selective distribution of [/sup 18/F]SP to the striatum in the four animals studied. Both [/sup 18/F]SP and [/sup 18/F]BEN may be suitable for PETT studies of neuroleptic receptors, but the in vivo kinetics of these compounds are markedly different from their in vitro receptor binding kinetics

Evaluation of Prostate Cancer Bone Metastases with 18F-NaF and 18F-Fluorocholine PET/CT.

Science.gov (United States)

Beheshti, Mohsen; Rezaee, Alireza; Geinitz, Hans; Loidl, Wolfgang; Pirich, Christian; Langsteger, Werner

2016-10-01

18 F-fluorocholine is a specific promising agent for imaging tumor cell proliferation, particularly in prostate cancer, using PET/CT. It is a beneficial tool in the early detection of marrow-based metastases because it excludes distant metastases and evaluates the response to hormone therapy. In addition, 18 F-fluorocholine has the potential to differentiate between degenerative and malignant osseous abnormalities because degenerative changes are not choline-avid; however, the agent may accumulate in recent traumatic bony lesions. On the other hand, 18 F-NaF PET/CT can indicate increased bone turnover and is generally used in the assessment of primary and secondary osseous malignancies, the evaluation of response to treatment, and the clarification of abnormalities on other imaging modalities or clinical data. 18 F-NaF PET/CT is a highly sensitive method in the evaluation of bone metastases from prostate cancer, but it has problematic specificity, mainly because of tracer accumulation in degenerative and inflammatory bone diseases. In summary, 18 F-NaF PET/CT is a highly sensitive method, but 18 F-fluorocholine PET/CT can detect early bone marrow metastases and provide greater specificity in the detection of bone metastases in patients with prostate cancer. However, the difference seems not to be significant. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Long-term quality assurance of [(18)F]-fluorodeoxyglucose (FDG) manufacturing.

Science.gov (United States)

Gaspar, Ludovit; Reich, Michal; Kassai, Zoltan; Macasek, Fedor; Rodrigo, Luis; Kruzliak, Peter; Kovac, Peter

2016-01-01

Nine years of experience with 2286 commercial synthesis allowed us to deliver comprehensive information on the quality of (18)F-FDG production. Semi-automated FDG production line using Cyclone 18/9 machine (IBA Belgium), TRACERLab MXFDG synthesiser (GE Health, USA) using alkalic hydrolysis, grade "A" isolator with dispensing robotic unit (Tema Sinergie, Italy), and automatic control system under GAMP5 (minus2, Slovakia) was assessed by TQM tools as highly reliable aseptic production line, fully compliant with Good Manufacturing Practice and just-in-time delivery of FDG radiopharmaceutical. Fluoride-18 is received in steady yield and of very high radioactive purity. Synthesis yields exhibited high variance connected probably with quality of disposable cassettes and chemicals sets. Most performance non-conformities within the manufacturing cycle occur at mechanical nodes of dispensing unit. The long-term monitoring of 2286 commercial synthesis indicated high reliability of automatic synthesizers. Shewhart chart and ANOVA analysis showed that minor non-compliances occurred were mostly caused by the declinations of less experienced staff from standard operation procedures, and also by quality of automatic cassettes. Only 15 syntheses were found unfinished and in 4 cases the product was out-of-specification of European Pharmacopoeia. Most vulnerable step of manufacturing was dispensing and filling in grade "A" isolator. Its cleanliness and sterility was fully controlled under the investigated period by applying hydrogen peroxide vapours (VHP). Our experience with quality assurance in the production of [(18)F]-fluorodeoxyglucose (FDG) at production facility of BIONT based on TRACERlab MXFDG production module can be used for bench-marking of the emerging manufacturing and automated manufacturing systems.

In vivo quantification of {sup 18}F-Fdg uptake in human placenta during early pregnancy

Energy Technology Data Exchange (ETDEWEB)

Zanotti-Fregonara, P.; Jan, S.; Trebossen, R.; Maroy, R. [CEA, DSV, I2BM, SHFJ, F-91401 Orsay (France); Champion, C. [Univ Paul Verlaine Metz, Lab Phys Mol et Collis, Inst Phys, Metz (France); Hindie, E. [Hop St Antoine, AP-HP, F-75571 Paris (France); Hindie, E. [Univ Paris 07, IMDCT, IUH, Ecole Doctorale B2T, F-75221 Paris (France)

2008-07-01

{sup 18}F-FDG is the most widely used PET radiopharmaceutical. Nevertheless, no data for {sup 18}F-FDG uptake in the human placenta have been reported. We recently reported on embryo dosimetry in a woman who underwent an {sup 18}F-FDG PET/CT scan during early pregnancy. In the present work we attempt an in vivo quantification of the {sup 18}F-FDG uptake by the placenta. The 27-y-old woman received 320 MBq of {sup 18}F-FDG for a follow-up study for Hodgkin's lymphoma and was later discovered to be pregnant (embryo age 8 wk). Imaging started 1 h after injection. The maximum placental tissue uptake (SUVmax) was 2.5. This value was conservatively attributed to the entire placental volume, i.e., 45 mL, a value representative of the average dimensions of a normal placenta at 8 wk. On the basis of these measurements, placenta {sup 18}F-FDG uptake in our patient was 0.19% of the injected activity. A Monte Carlo simulation was used to derive the photon dose to the embryo from the placenta (0.022 * 10{sup -2} mGy per MBq of injected {sup 18}F-FDG) and from the surrounding amniotic fluid (0.017 * 10{sup -2} mGy MBq{sup -1}). This increases our previously calculated dose (3.3 * 10{sup -2} mGy MBq{sup -1}) by only a small fraction (1.18%), which does not justify modifying the previous estimate given the overall uncertainties. (authors)

Imaging of accidental contamination with F-18-solution; a quick trouble-shooting procedure

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Kalevi Kairemo

2016-01-01

Full Text Available To the best of our knowledge, imaging of accidental exposure to radioactive fluorine-18 (F-18 due to liquid spill has not been described earlier in the scientific literature. The short half-life of F-18 (t½=110 min, current radiation safety requirements, and Good Manufacturing Practice (GMP regulations on radiopharmaceuticals have restrained the occurrence of these incidents. The possibility of investigating this type of incidents by gamma and positron imaging is also quite limited. Additionally, a quick and precise analysis of radiochemical contamination is cumbersome and sometimes challenging if the spills of radioactive materials are low in activity. Herein, we report a case of accidental F-18 contamination in a service person during a routine cyclotron maintenance procedure. During target replacement, liquid F-18 was spilled on the person responsible for the maintenance. The activities of spills were immediately measured using contamination detectors, and the photon spectrum of contaminated clothes was assessed through gamma spectroscopy. Despite protective clothing, some skin areas were contaminated, which were then thoroughly washed. Later on, these areas were imaged, using positron emission tomography (PET, and a gamma camera (including spectroscopy. Two contaminated skin areas were located on the hand (9.7 and 14.7 cm2, respectively, which showed very low activities (19.0 and 22.8 kBq respectively at the time of incident. Based on the photon spectra, F-18 was confirmed as the main present radionuclide. PET imaging demonstrated the shape of these contaminated hot spots. However, the measured activities were very low due to the use of protective clothing. With prompt action and use of proper equipments at the time of incident, minimal radionuclide activities and their locations could be thoroughly analyzed. The cumulative skin doses of the contaminated regions were calculated at 1.52 and 2.00 mSv, respectively. In the follow-up, no skin

Estimation of patient dose in 18 F-FDG and 18 F-FDOPA PET/CT examinations

Directory of Open Access Journals (Sweden)

Aruna Kaushik

2013-01-01

Full Text Available Purpose: To estimate specific organ and effective doses to patients resulting from the 18 F-FDG ( 18 F-2-deoxy-D-glucose and 18 F-FDOPA (6-fluoro-( 18 F-L-3, 4-dihydroxyphenylalanine PET/CT examinations for whole body and brain. Materials and Methods: Three protocols for whole body and three for brain PET/CT were used. The CTDI values were measured using standard head and body CT phantoms and also computed using a software CT-Expo for dose evaluation from the CT component. OLINDA software based on MIRD method was used for estimating doses from the PET component of the PET/CT examination. Results: The organ doses from 18 F-FDG and 18 F-FDOPA whole body and brain PET/CT studies were estimated. The total effective dose from a typical protocol of whole body PET/CT examination was 14.4 mSv for females and 11.8 mSv for male patients from 18 F-FDG, whereas it was 11 mSv for female and 9.1 mSv for male patients from 18 F-FDOPA. The total effective doses from a typical protocol for PET/CT studies of brain was 6.5 mSv for females and 5.1 mSv for males from 18 F-FDG whereas it was 3.7 mSv for females and 2.8 mSv for males from 18 F-FDOPA. Conclusions: The effective radiation doses from whole body PET/CT examination was approximately 4-8 times higher than the background radiation dose from both 18 F-FDG and 18 F-FDOPA scans, while it was 1-3 times the background radiation dose from PET/CT scans of brain.

Re-thinking the role of radiometal isotopes: Towards a future concept for theranostic radiopharmaceuticals.

Science.gov (United States)

Notni, Johannes; Wester, Hans-Jürgen

2018-03-01

The potential and future role of certain metal radionuclides, for example, 44 Sc, 89 Zr, 86 Y, 64 Cu, 68 Ga, 177 Lu, 225 Ac, and 213 Bi, and several terbium isotopes has been controversially discussed in the past decades. Furthermore, the possible benefits of "matched pairs" of isotopes for tandem applications of diagnostics and therapeutics (theranostics) have been emphasized, while such approaches still have not made their way into routine clinical practice. Analysis of bibliographical data illustrates how popularity of certain nuclides has been promoted by cycles of availability and applications. We furthermore discuss the different practical requirements for diagnostic and therapeutic radiopharmaceuticals and the resulting consequences for efficient development of clinically useful pairs of radionuclide theranostics, with particular emphasis on the underlying economical factors. Based on an exemplary assessment of overall production costs for 68 Ga and 18 F radiopharmaceuticals, we venture a look into the future of theranostics and predict that high-throughput PET applications, that is, diagnosis of frequent conditions, will ultimately rely on 18 F tracers. PET radiometals will occupy a niche in the clinical low-throughput sector (diagnosis of rare diseases), but above all, dominate preclinical research and clinical translation. Matched isotope pairs will be of lesser relevance for theranostics but may become important for future PET-based therapeutic dosimetry. Copyright © 2017 John Wiley & Sons, Ltd.

Intelligent control of liquid transfer for the automated synthesis of positron emitting radiopharmaceuticals

International Nuclear Information System (INIS)

Iwata, Ren; Ido, Tatsuo; Yamazaki, Shigeki

1990-01-01

A method for the intelligent control of liquid transfer, developed for automated synthesis of 2-deoxy-2-[ 18 F]fluoro-D-glucose from [ 18 F]fluoride, is described. A thermal mass flow controller coupled to a personal computer is used to monitor conditions for transferring or passing liquid through a tube or a column. Using this sensor a computer can detect completion of liquid transfer, dispense a stock solution and check the setup conditions of the system. The present feedback control can be readily adapted to other automated syntheses of positron emitting radiopharmaceuticals. (author)

Evaluation of steam sterilization conditions for [18F]fludeoxyglucose

International Nuclear Information System (INIS)

Santos, Priscilla F.; Nascimento, Leonardo T.; Valente, Eduardo S.; Silva, Juliana B.; Silveira, Marina B.; Ferreira, Soraya Z.

2011-01-01

[ 18 F]Flu deoxyglucose ( 18 FDG) is the most commonly used radiopharmaceutical for positron emission tomography. Sterile filtration of the final product into sterile vials using 0.22 μm filter membrane is usually adopted for 18 FDG. However, Good Manufacturing Practice (GMP) guidelines recommend heat sterilization as the method of choice to ensure sterility of pharmaceutical preparations. The aim of this study was to essay different steam sterilization conditions in order to choose the best one for 18 FDG. Three different sterilization conditions were essayed. The first one at 121 deg C for 15 minutes, the second one at 135 deg C for 3.5 minutes and the third one at 133 deg C for 2 minutes. 18 FDG pH-formulation was kept around 6.0. At the end of autoclave cycles, 18 FDG sterility was evaluated by direct inoculation of 18 FDG in culture media and radiochemical purity was determined by TLC and HPLC. Results demonstrated that all essayed conditions were able to ensure 18 FDG sterility, but caused a decrease in radiochemical purity of 18 FDG. Autoclave cycle at 133 deg C for 2 minutes was the best essayed condition for 18 FDG terminal sterilization, once it provided the greater radiochemical purity value and took less time. 18 FDG was able to meet specifications after autoclave cycles, what supports the application of steam sterilization in routine 18 FDG production, in compliance with GMP. (author)

Effect of blood activity on dosimetric calculations for radiopharmaceuticals

Science.gov (United States)

Zvereva, Alexandra; Petoussi-Henss, Nina; Li, Wei Bo; Schlattl, Helmut; Oeh, Uwe; Zankl, Maria; Graner, Frank Philipp; Hoeschen, Christoph; Nekolla, Stephan G.; Parodi, Katia; Schwaiger, Markus

2016-11-01

The objective of this work was to investigate the influence of the definition of blood as a distinct source on organ doses, associated with the administration of a novel radiopharmaceutical for positron emission tomography-computed tomography (PET/CT) imaging—(S)-4-(3-18F-fluoropropyl)-L-glutamic acid (18F-FSPG). Personalised pharmacokinetic models were constructed based on clinical PET/CT images from five healthy volunteers and blood samples from four of them. Following an identifiability analysis of the developed compartmental models, person-specific model parameters were estimated using the commercial program SAAM II. Organ doses were calculated in accordance to the formalism promulgated by the Committee on Medical Internal Radiation Dose (MIRD) and the International Commission on Radiological Protection (ICRP) using specific absorbed fractions for photons and electrons previously derived for the ICRP reference adult computational voxel phantoms. Organ doses for two concepts were compared: source organ activities in organs parenchyma with blood as a separate source (concept-1); aggregate activities in perfused source organs without blood as a distinct source (concept-2). Aggregate activities comprise the activities of organs parenchyma and the activity in the regional blood volumes (RBV). Concept-1 resulted in notably higher absorbed doses for most organs, especially non-source organs with substantial blood contents, e.g. lungs (92% maximum difference). Consequently, effective doses increased in concept-1 compared to concept-2 by 3-10%. Not considering the blood as a distinct source region leads to an underestimation of the organ absorbed doses and effective doses. The pronounced influence of the blood even for a radiopharmaceutical with a rapid clearance from the blood, such as 18F-FSPG, suggests that blood should be introduced as a separate compartment in most compartmental pharmacokinetic models and blood should be considered as a distinct source in

Optimization of internal monitoring methodology of 18F in the form of 18FDG at the CRCN-NE, Recife, Pernambuco, Brazil

International Nuclear Information System (INIS)

Lacerda, Isabelle V.B.; Xavier, Aline C.S.; Lima, Fabiana F.; Oliveira, Mercia L.; Oliveira, Cassio M.; Silva, Tania V. da; Alonso, Thessa C.; Silva, Teogenes A. da

2011-01-01

The work aims to optimize and improve the efficiency of the internal monitoring technique developed at Centro Regional de Ciencias Nucleares do Nordeste for F-18 in form of F-18DG radiopharmaceuticals. It was performed two assays for the methodology developed. The first was performed in a makeshift room, while the second was performed in a room with walls reinforced with concrete. The detection system was a NaI (Tl) 3 x 3 s cintillation detector, coupled with the software Genie 2000. In order to obtain the calibration factor, a brain phantom containing 22 Na liquid source was measured. The interpretation of the bioassay data was performed using the biokinetic models provided by the ICRP 53 and edited by software AIDE-version 6, which gives the fraction of activity retained in the organs as a function of time. The sensitivities of detection were similar, resulting in a minimum detectable dose below 1 mSv, as recommended by the IAEA. (author)

Synthesis and evaluation of 7α-(3-[18F]fluoropropyl) estradiol

International Nuclear Information System (INIS)

Okamoto, Mayumi; Naka, Kyosuke; Kitagawa, Yuya; Ishiwata, Kiichi; Yoshimoto, Mitsuyoshi; Shimizu, Isao; Toyohara, Jun

2015-01-01

Introduction: Several lines of evidence suggest that C-7α-substituted estradiol derivatives are well tolerated by estrogen receptor (ER). In line with this hypothesis, we are interested in the design and synthesis of C-7α-substituted estrogens as molecular probes to visualize ER function. Methods: We have synthesized 7α-(3-[ 18 F]fluoropropyl) estradiol (C3-7α-[ 18 F]FES) as a potential radiopharmaceutical for ER imaging by positron emission tomography (PET). In vitro receptor binding and in vivo biodistribution and blocking studies in mature female mice, and in vivo metabolite analysis were carried out. Furthermore, in vivo ER-selective uptake was confirmed using ER-positive T-47D and ER-negative MDA-MB-231 tumor-bearing mice. We also compared the in vivo biodistribution of C3-7α-[ 18 F]FES with 16α-[ 18 F]FES. Results: C3-7α-[ 18 F]FES was produced in moderate yields (30.7% ± 15.1%, decay corrected) with specific activity of 32.0 ± 18.1 GBq/μmol (EOS). The in vitro binding affinity of C3-7α-FES to the ERα isoform was sufficient and equivalent to that of estradiol. C3-7α-[ 18 F]FES showed selective uptake in ER-rich tissues, such as the uterus (4.7%ID/g ± 1.2%ID/g at 15 minutes) and ovary (4.0%ID/g ± 1.0%ID/g at 5 minutes). The tissue time activity curves of these organs showed reversible kinetics, indicating suitability for quantitative analysis. The highest contrast was obtained at 120 minutes after injection of C3-7α-[ 18 F]FES in the uterus (uterus/blood = 18, uterus/muscle = 17.3) and ovary (ovary/blood = 6.3, ovary/muscle = 6.0). However, the level of selective uptake of C3-7α-[ 18 F]FES was significantly lower than that of 16α-[ 18 F]FES. Most radioactivity in the uterus was detected in unchanged form, although peripherally C3-7α-[ 18 F]FES was rapidly degraded to hydrophilic metabolites. In accordance with this peripheral metabolism, gradual increases in bone radioactivity were observed, indicating defluorination. Coinjection with

Current evaluation of the clinical utility of fluoromethyl choline-(18F) PET/CT in prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Talbot, Jean-Noel [Hopital Tenon AP-HP, Paris (France); Universite Pierre et Marie Curie, Paris (France); E-mail: jean-noel.talbot@tnn.ap-hop-paris.fr; Chevalme, Yanna-Marina [Agence Francaise de Securite Sanitaire des Produits de Sante (AFSSAPS), St Denis (France)

2008-12-15

This short review is dedicated to the current status of the assessment of a new PET radiopharmaceutical, fluoromethylcholine-(18F) or FCH, which is taken-up by prostate cancer tissue, in contrary to fluorodeoxyglucose- (18F) or FDG. It seems that FCH could become 'the FDG of prostate cancer', with the same type of achievements (detection of distant metastases and of occult recurrences, restaging prior to invasive treatments), and the same drawbacks (false negative results in case of small lesions, in particular lymph nodes metastases, and false positive results in case of infection/inflammation, in particular prostatitis). Current evidence is summarised and discussed for each of the potential settings of FCH PET/CT imaging in prostate cancer. The perspectives for granting a marketing authorisation to a FCH preparation are briefly analysed. (author)

Validation of a new analytical procedure for determination of residual solvents in [18F]FDG by gas chromatography

International Nuclear Information System (INIS)

Costa, Flávia M.; Costa, Cassiano L.S.; Silva, Juliana B.; Ferreira, Soraya M.Z.M.D.

2017-01-01

Fludeoxyglucose F 18 ([ 18 F]FDG) is the most used radiopharmaceutical for positron emission tomography, especially on oncology. Organic solvents such as ether, ethanol and acetonitrile might be used in the synthesis of [ 18 F]FDG; however, they might not be completely removed during purification steps. The determination of residual solvents in [ 18 F]FDG is required in the European Pharmacopoeia (EP) and the United States Pharmacopeia (USP) monographs. While the procedure described in the EP is quite general, the one described in the USP requires a long runtime (about 13 minutes). In this work a simple and fast (4-minute) analytical procedure was developed and validated for determination of residual solvents in [ 18 F]FDG. Analyses were carried out in a Perkin Elmer gas chromatograph equipped with a flame ionization detector. The separation was obtained on a 0.53-mm x 30 m fused-silica column. Validation included the evaluation of various parameters, such as: specificity, linearity and range, limits of detection and quantitation, precision (repeatability and intermediate precision), accuracy, and robustness. Results were found to be within acceptable limits, indicating the developed procedure is suitable for its intended application. Considering the short half-life of fluorine-18 (109.7 minutes), this new method could be a valuable alternative for routine quality control of [ 18 F]FDG. (author)

Impact on estrogen receptor binding and target tissue uptake of [18F]fluorine substitution at the 16α-position of fulvestrant (faslodex; ICI 182,780)

International Nuclear Information System (INIS)

Seimbille, Yann; Benard, Francois; Rousseau, Jacques; Pepin, Emilie; Aliaga, Antonio; Tessier, Guillaume; Lier, Johan E. van

2004-01-01

Fulvestrant (Faslodex; ICI 182,780) is a pure estrogen receptor (ER) antagonist recently approved for the treatment of hormone-sensitive breast cancer in post-menopausal women with disease progression following antiestrogen therapy. Fulvestrant strongly binds to the ER and its mode of action consists of inhibition of ER dimerization leading to a down regulation of ER protein cellular levels. With the aim to develop a probe for positron emission tomography (PET) imaging capable of predicting the potential therapeutic efficacy of selective ER modulators (SERM), we prepared three new 16α-[ 18 F]fluoro-fulvestrant derivatives. These new radiopharmaceuticals were evaluated for their binding affinity to the human ERα and for their target tissue uptake in immature female rats. Substitution of one of the side-chain F-atoms of fulvestrant for 18 F would have led to a product of low specific activity; instead we selected the 16α-position for 18 F-labeling, which at least in the case of estradiol (ES) is well tolerated by the ER. Radiochemical synthesis proceeds by stereoselective introduction of the [ 18 F]fluoride at the 16- 18 F-position of fulvestrant via opening of an intermediate O-cyclic sulfate followed by hydrolysis of the protecting methoxymethyl (MOM) ether and sulfate groups. Three analogs with different oxidation states of the side chain sulfur, i.e. sulfide, sulfone or sulfoxide (fulvestrant) were prepared. Introduction of the 16 18 F-fluorine led to a dramatic decrease of the apparent binding affinity for ER, as reported by Wakeling et al. (Cancer Res. 1991;51:3867-73). Likewise, in vivo ER-mediated uterus uptake values in immature female rats were disappointing. Overall, our findings suggest that these new PET radiopharmaceuticals are not suitable as tracers to predict ER(+) breast cancer response to hormonal therapy with selective ER modulators

The fluorodediazonation - a method for n.c.a.-18F-labelling of aromatic substrates

International Nuclear Information System (INIS)

Zwernemann, O.

1991-06-01

For the positron emission tomography (PET) applications, radiopharmaceuticals are required that are labelled with short-lived positron emitters. Fluorine-18 has become the leading radionuclide used for PET, due to its favourable physical properties. However, the labelling of aromatic substances with fluorine-18 with the methods available presents problems not encountered with aliphatic compounds. The decomposition of aromatic diazonium salts opens up feasible ways of preparing a broad range of labelled compounds. The dissertation investigated the possibilities of labelling with fluorine-18 by way of dediazonation on the standard substrate p-Toluidyl diazonium ion. The results reported show that the method of fluorodediazonation is an interesting further method for F-18 labelling of aromatic substrates in addition to the hitherto applied techniques. It allows carrier-free labelling of a large group of substances which cannot be fluorinated via direct nucleophilicity. (BBR) [de

The Effect of the Prosthetic Group on the Pharmacologic Properties of 18F-labeled Rhodamine B, a Potential Myocardial Perfusion Agent for PET

Science.gov (United States)

Bartholomä, Mark D.; Gottumukkala, Vijay; Zhang, Shaohui; Baker, Amanda; Dunning, Patricia; Fahey, Frederic H.; Treves, S. Ted; Packard, Alan B.

2013-01-01

We recently reported the development of the 2-[18F]fluoroethyl ester of rhodamine B as a potential positron emission tomography (PET) tracer for myocardial perfusion imaging. This compound, which was prepared using a [18F]fluoroethyl prosthetic group, has significant uptake in the myocardium in rats, but also demonstrates relatively high liver uptake and is rapidly hydrolyzed in vivo in mice. We have now prepared 18F-labeled rhodamine B using three additional prosthetic groups (propyl, diethylene glycol, and triethylene glycol) and found that the prosthetic group has a significant effect on the in vitro and in vivo properties of these compounds. Of the esters prepared to date, the diethylene glycol ester is superior in terms of in vitro stability and pharmacokinetics. These observations suggest that the prosthetic group plays a significant role in determining the pharmacological properties of 18F-labeled compounds. They also support the value of continued investigation of 18F-labeled rhodamines as PET radiopharmaceuticals for myocardial perfusion imaging. PMID:23210516

Tritium in [18O]water containing [18F]fluoride for [18F]FDG synthesis

International Nuclear Information System (INIS)

Ito, Shigeki; Saze, Takuya; Sakane, Hitoshi; Ito, Satoshi; Ito, Shinichi; Nishizawa, Kunihide

2004-01-01

The presence of tritium in enriched [ 18 O]water irradiated with 9.6 MeV protons used to produce [ 18 F]fluoride by the 18 O(p, n) 18 F reaction was inferred from the cross sections and threshold energies of the 18 O(p, t) 16 O reaction, and the existence of tritium was confirmed experimentally. Tritium was also detected in both [ 18 O]water recovered for recycling and waste acetonitrile solutions. The purified [ 18 F]FDG was not contaminated with 3 H. The amount of 3 H discharged into the air was far less than the International Basic Safety Standard Level

Difficulties and aspects to take into account in the production, use and distribution of new radiopharmaceuticals PET

International Nuclear Information System (INIS)

Sanchez, R.; Rayo, J.I.; Serrano, J.; Infante, J.; Luz Dominguez, M.; Garcia, L.; Duran, C.

2008-01-01

This article seeks to describe the requirements, legal and technical, for the production, distribution and use of new radiopharmaceuticals PET (other than the 18 F.D.G.), describing the legislative framework in which we find ourselves, the characteristics of a production and types of synthesis and existing modules. A list of susceptible radiopharmaceuticals is presented that are being currently used in nuclear medicine by specifying the real possibilities of their production and use and which are the difficulties we face

Syntheses of 2-nitroimidazole derivatives conjugated with 1,4,7-triazacyclononane-N,N'-diacetic acid labeled with F-18 using an aluminum complex method for hypoxia imaging.

Science.gov (United States)

Hoigebazar, Lathika; Jeong, Jae Min; Lee, Ji-Youn; Shetty, Dinesh; Yang, Bo Yeun; Lee, Yun-Sang; Lee, Dong Soo; Chung, June-Key; Lee, Myung Chul

2012-04-12

Hypoxia imaging is important for diagnosis of ischemic diseases, and thus various (18)F-labeled radiopharmaceuticals have been developed. However, (18)F-labeling requires multistep procedures including azeotropic distillation, which is complicated and difficult to automate. Recently, (18)F-labeling method using Al-F complex in aqueous solution was devised that offered a straightforward (18)F-labeling procedure. We synthesized nitroimidazole derivatives conjugated with 1,4,7-triazacyclononane-1,4-diacetic acid (NODA) that can be labeled with (18)F using Al-F complex and examined their radiochemistries, in vitro and in vivo biological properties, and animal PET imaging characteristics. We found that the synthesized derivatives have excellent (18)F-labeling efficiencies, high stabilities, specific uptakes in cultured hypoxic tumor cells, and high tumor to nontumor ratios in xenografted mice. Furthermore, the derivatives were labeled with (18)F in a straightforward manner within 15 min at high labeling efficiencies and radiochemical purities. In conclusion, (18)F-labeled NODA-nitroimidazole conjugates were developed and proved to be promising hypoxia PET agents. © 2012 American Chemical Society

PET/CT with 18F-choline: Physiological whole bio-distribution in male and female subjects and diagnostic pitfalls on 1000 prostate cancer patients: 18F-choline PET/CT bio-distribution and pitfalls. A southern Italian experience.

Science.gov (United States)

Calabria, Ferdinando; Chiaravalloti, Agostino; Cicciò, Carmelo; Gangemi, Vincenzo; Gullà, Domenico; Rocca, Federico; Gallo, Gianpasquale; Cascini, Giuseppe Lucio; Schillaci, Orazio

2017-08-01

The 11 C/ 18 F-choline is a PET/CT radiopharmaceutical useful in detecting tumors with high lipogenesis. 11 C/ 18 F-choline uptake can occur in physiological conditions or tumors. The knowledge of its bio-distribution is essential to recognize physiologic variants or diagnostic pitfalls. Moreover, few information are available on the bio-distribution of this tracer in female patients. Our aim was to discuss some documented 18 F-choline PET/CT pitfalls in prostate cancer patients. Our secondary aim was to describe the 18 F-choline bio-distribution in the female body. We collected diagnostic pitfalls in three PET centers examining 1000 prostate cancer by 18 F-choline PET/CT. All pitfalls were ensured by follow-up, imaging and/or histology. We also performed whole body 18 F-choline PET/CT in 5 female patients. 169/1000 (16.9%) patients showed pitfalls not owing to prostate cancer. These findings were due to inflammation, benign tumors while, in 1% of examined patients, a concomitant neoplasm was found. In the female body, the breast showed low physiological uptake. The accurate knowledge of 18 F-choline PET/CT bio-distribution and diagnostic pitfalls is essential. Correlative imaging and histological exam are often necessary to depict pitfalls. In women, the uptake in the breast is due to the physiological gradient of 18 F-choline uptake in the exocrine glands. Our results confirm the possibility of 18 F-choline uptake in several diseases other than prostate cancer. However, our experience was acquired on a large population and shows that a conspicuous amount of 18 F-choline diagnostic pitfalls are easily recognizable and attributable to inflammation. A new advance in knowledge is the minimal difference in terms of physiological tracer bio-distribution between male and female patients. The knowledge of the physiological bio-distribution and of the potential pitfalls linked of a tracer could help physicians to choose the best diagnostic and therapeutic approaches for a

Impact on estrogen receptor binding and target tissue uptake of [{sup 18}F]fluorine substitution at the 16{alpha}-position of fulvestrant (faslodex; ICI 182,780)

Energy Technology Data Exchange (ETDEWEB)

Seimbille, Yann; Benard, Francois E-mail: francois.benard@USherbrooke.ca; Rousseau, Jacques; Pepin, Emilie; Aliaga, Antonio; Tessier, Guillaume; Lier, Johan E. van

2004-08-01

Fulvestrant (Faslodex; ICI 182,780) is a pure estrogen receptor (ER) antagonist recently approved for the treatment of hormone-sensitive breast cancer in post-menopausal women with disease progression following antiestrogen therapy. Fulvestrant strongly binds to the ER and its mode of action consists of inhibition of ER dimerization leading to a down regulation of ER protein cellular levels. With the aim to develop a probe for positron emission tomography (PET) imaging capable of predicting the potential therapeutic efficacy of selective ER modulators (SERM), we prepared three new 16{alpha}-[{sup 18}F]fluoro-fulvestrant derivatives. These new radiopharmaceuticals were evaluated for their binding affinity to the human ER{alpha} and for their target tissue uptake in immature female rats. Substitution of one of the side-chain F-atoms of fulvestrant for {sup 18}F would have led to a product of low specific activity; instead we selected the 16{alpha}-position for {sup 18}F-labeling, which at least in the case of estradiol (ES) is well tolerated by the ER. Radiochemical synthesis proceeds by stereoselective introduction of the [{sup 18}F]fluoride at the 16-{sup 18}F-position of fulvestrant via opening of an intermediate O-cyclic sulfate followed by hydrolysis of the protecting methoxymethyl (MOM) ether and sulfate groups. Three analogs with different oxidation states of the side chain sulfur, i.e. sulfide, sulfone or sulfoxide (fulvestrant) were prepared. Introduction of the 16{sup 18}F-fluorine led to a dramatic decrease of the apparent binding affinity for ER, as reported by Wakeling et al. (Cancer Res. 1991;51:3867-73). Likewise, in vivo ER-mediated uterus uptake values in immature female rats were disappointing. Overall, our findings suggest that these new PET radiopharmaceuticals are not suitable as tracers to predict ER(+) breast cancer response to hormonal therapy with selective ER modulators.

MCNPX dosimetry and radiation-induced cancer risk estimation from 18F-FDG pediatric PET at Brazilian population

International Nuclear Information System (INIS)

Mendes, Bruno M.; Fonseca, Telma C.F.; Campos, Tarcisio P.R.

2017-01-01

Positron emission tomography (PET) using 18 F-FDG has increased significantly in pediatric patients. PET with 18 F-FDG has often been applied in oncology. Cancer induction is one of the main stochastic risk from exposure to ionizing radiation of 18 F-FDG. Radiation-induced cancer risk estimation due to medical exposures is an important tool for risk/benefit assessing. The objective was to perform dosimetry and estimate the risk of cancer induction due to pediatric use of 18 F-FDG. MCNPX Computational dosimetry was performed to estimate organ absorbed doses resulting from 18 F-FDG pediatric use. Two voxelized phantoms, kindly provided by the GSF - Helmholtz Zentrum, were used: 'Child' - 7 years child and 'Baby' 8-week-old infant. ICRP-128 publication provided the radiopharmaceutical biodistribution of F-18. Tables containing organ absorbed dose and effective dose per unit of injected activity for the two phantoms were obtained. The injected activities were estimated according to data provided in the literature. Images of the absorbed dose distribution were generated from both models. The BEIR VII methodology was used to calculate the risk of cancer induction. The risk of cancer induction (per imaging procedure) for the seven-year-old child was (0.09% ♂ and 0.15% ♀) and for the eight-week old baby was (0.11% ♂ and 0.21% ♀). The 18 F-FDG absorbed dose distribution in the children and infants showed some divergences in comparison to adult data. Probably, the biokinetic data used to children and infants is the main reason for this disconnection. (author)

Validation of a new analytical procedure for determination of residual solvents in [{sup 18}F]FDG by gas chromatography

Energy Technology Data Exchange (ETDEWEB)

Costa, Flávia M.; Costa, Cassiano L.S.; Silva, Juliana B.; Ferreira, Soraya M.Z.M.D., E-mail: flaviabiomedica@yahoo.com.br [Centro de Desenvolvimento da Tecnologia Nuclear (UPPR/CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Unidade de Pesquisa e Produção de Radiofármacos

2017-07-01

Fludeoxyglucose F 18 ([{sup 18}F]FDG) is the most used radiopharmaceutical for positron emission tomography, especially on oncology. Organic solvents such as ether, ethanol and acetonitrile might be used in the synthesis of [{sup 18}F]FDG; however, they might not be completely removed during purification steps. The determination of residual solvents in [{sup 18}F]FDG is required in the European Pharmacopoeia (EP) and the United States Pharmacopeia (USP) monographs. While the procedure described in the EP is quite general, the one described in the USP requires a long runtime (about 13 minutes). In this work a simple and fast (4-minute) analytical procedure was developed and validated for determination of residual solvents in [{sup 18}F]FDG. Analyses were carried out in a Perkin Elmer gas chromatograph equipped with a flame ionization detector. The separation was obtained on a 0.53-mm x 30 m fused-silica column. Validation included the evaluation of various parameters, such as: specificity, linearity and range, limits of detection and quantitation, precision (repeatability and intermediate precision), accuracy, and robustness. Results were found to be within acceptable limits, indicating the developed procedure is suitable for its intended application. Considering the short half-life of fluorine-18 (109.7 minutes), this new method could be a valuable alternative for routine quality control of [{sup 18}F]FDG. (author)

PET/CT comparing 68Ga-DOTATATE and other radiopharmaceuticals and in comparison with CT/MRI for the localization of sporadic metastatic pheochromocytoma and paraganglioma

International Nuclear Information System (INIS)

Janssen, Ingo; Chen, Clara C.; Millo, Corina M.; Herscovitch, Peter; Ling, Alexander; Taieb, David; Lin, Frank I.; Adams, Karen T.; Wolf, Katherine I.; Pacak, Karel; Fojo, Antonio T.; Buchmann, Inga; Kebebew, Electron

2016-01-01

Pheochromocytomas/paragangliomas (PPGLs) and their metastases are tumors that predominantly express somatostatin receptor 2 (SSR2). 68 Ga-DOTA(0)-Tyr(3)-octreotate ( 68 Ga-DOTATATE) is a PET radiopharmaceutical with both high and selective affinity for SSRs. The purpose of this study was to evaluate the utility of 68 Ga-DOTATATE in comparison with other specific and nonspecific radiopharmaceuticals recommended in the current guidelines for the localization of metastatic sporadic PPGL by PET/CT. This prospective study included 22 patients (15 men, 7 women; aged 50.0 ± 13.9 years) with confirmed metastatic PPGL, a negative family history for PPGL, and negative genetic testing, who underwent 68 Ga-DOTATATE, 18 F-fluoro-2-deoxy-D-glucose ( 18 F-FDG) PET/CT, and CT/MRI. Only 12 patients underwent an additional 18 F-fluorodihydroxyphenylalanine ( 18 F-FDOPA) PET/CT scan and only 11 patients underwent an additional 18 F-fluorodopamine ( 18 F-FDA) PET/CT scan. The rates of detection of metastatic lesions were compared among all the imaging studies. A composite of all functional and anatomical imaging studies served as the imaging comparator. 68 Ga-DOTATATE PET/CT showed a lesion-based detection rate of 97.6 % (95 % confidence interval, CI, 95.8 - 98.7 %). 18 F-FDG PET/CT, 18 F-FDOPA PET/CT, 18 F-FDA PET/CT, and CT/MRI showed detection rates of 49.2 % (CI 44.5 - 53.6 %; p < 0.01), 74.8 % (CI 69.0 - 79.9 %; p < 0.01), 77.7 % (CI 71.5 - 82.8 %; p < 0.01), and 81.6 % (CI 77.8 - 84.8 %; p < 0.01), respectively. The results of this study demonstrate the superiority of 68 Ga-DOTATATE PET/CT in the localization of sporadic metastatic PPGLs compared to all other functional and anatomical imaging modalities, and suggest modification of future guidelines towards this new imaging modality. (orig.)

On the synthesis of radiofluorinated amino acids by isotope exchange based on the example of 6-[{sup 18}F]Fluor-L-DOPA; Zur Synthese radiofluorierter aromatischer Aminosaeuren mittels Isotopenaustausch am Beispiel von 6-[{sup 18}F]Fluor-L-DOPA

Energy Technology Data Exchange (ETDEWEB)

Wagner, F M

2008-06-15

In nuclear medical diagnosis, 6-[{sup 18}F]fluoro-L-3,4-dihydroxyphenylalanine (6-[{sup 18}F]fluoro-LDOPA), an analogue of L-DOPA, is one of the few established radiopharmaceuticals used for the in vivo investigation of the presynaptic dopaminergic metabolism and of some kind of tumours via Positron Emission Tomography (PET). The presently used method of preparation of the radiotracer by electrophilic labelling is limited to low amounts of activity at high costs. Known nucleophilic syntheses, however, result either in insufficient enantiomeric purity or the known multi-step syntheses are hard to automate, due to their complexity. During this work a novel, easy to automate alternative for the preparation of 6-[{sup 18}F]fluoro-L-DOPA, was developed and evaluated, using a direct nucleophilic {sup 18}F-fluorination of a protected amino acid derivative. The resulting product has a very high enantiomeric purity. At first, the general suitability of the (S)-BOC-BMI-derivatives for the synthesis of {sup 18}F-labelled amino acids, used in this work, was investigated using a less complex precursor, which resulted in the amino acid 6-[{sup 18}F]fluoro-L-m-tyrosin via acidic hydrolysis. The preparation of a useful precursor for the nucleophilic {sup 18}F-isotope substitution, namely the (2S,5S)-tert.-butyl- 5-(2-fluoro-5-formylbenzyl)-2-tert.-butyl-3-methyl-4-oxoimidazolidine-1-carboxylate, was investigated in three general different ways. At first it was tried to obtain this product via formylation after coupling with the BOC-BMI, secondly via {alpha},{beta}-dehydro amino acid derivatives and finally via a systematic multi-step synthesis. Only the last mentioned way resulted in a precursor with sufficient purity that could be labelled. The radiochemical yield of the isotopic exchange was about 60 %. In the next step, the presented concept was modified to synthesize a precursor for the preparation of 6-[{sup 18}F]fluoro-L-DOPA. Only a combination of the protecting groups

Computational chemistry and metal-based radiopharmaceuticals

International Nuclear Information System (INIS)

Neves, M.; Fausto, R.

1998-01-01

Computer-assisted techniques have found extensive use in the design of organic pharmaceuticals but have not been widely applied on metal complexes, particularly on radiopharmaceuticals. Some examples of computer generated structures of complexes of In, Ga and Tc with N, S, O and P donor ligands are referred. Besides parameters directly related with molecular geometries, molecular properties of the predicted structures, as ionic charges or dipole moments, are considered to be related with biodistribution studies. The structure of a series of oxo neutral Tc-biguanide complexes are predicted by molecular mechanics calculations, and their interactions with water molecules or peptide chains correlated with experimental data of partition coefficients and percentage of human protein binding. The results stress the interest of using molecular modelling to predict molecular properties of metal-based radiopharmaceuticals, which can be successfully correlated with results of in vitro studies. (author)

Recoil 18F-chemistry in fluoroalkanes

International Nuclear Information System (INIS)

Linde, K.D. van der.

1982-01-01

This thesis describes the study of the chemical reactions of recoil 18 F-atoms in gaseous fluoromethanes and fluoroethanes. A brief survey of the organic hot atom chemistry is given in Chapter I. Chapter II deals with the experimental procedures used in this investigation. The irradiation facilities, the vapour phase radio-chromatography and the identification, including the synthesis of some fluorocarbons, are described in detail. Chapter III consists of a study on the applicability of perfluoropropene, C 3 F 6 , as scavenger for thermal 18 F-atoms and radicals. Chapters IV, V, VI and VII deal with 18 F-recoil chemistry in gaseous fluoroethanes, using H 2 S as scavenger. Chapter VIII is a short discussion on the hot 18 F-atom based production of 18 F-labeled organic compounds via decay of the intermediate 18 Ne. A target system is proposed for production of this isotope in high energy and ultra high flux particle beams, which possibly would become available in fast breeders and fusion reactors. (Auth.)

Current status of PET imaging of differentiated thyroid cancer with second generation radiopharmaceuticals

International Nuclear Information System (INIS)

Lauri, C.; Di Traglia, S.; Galli, F.; Pizzichini, P.; Signore, A.

2015-01-01

Although the prognosis of differentiated thyroid cancer (DTC) is favorable, some histotypes show worst clinical outcome and higher risk of recurrence. Serum thyroglobulin (Tg) levels and 131 I-whole-body-scan (WBS), together with neck ultrasound (US), represent the golden standard for DTC follow-up. Nevertheless, the relatively high frequency of patients with high Tg levels and negative WBS requires further investigations by using new imaging modalities. The availability of whole body positron emission tomography (PET) methods, in parallel with the advances in radiochemistry, offer a wide substrate for many solutions. To this day 18 F-fluoro-deoxy-glucose ( 18 F-FDG) PET/CT still represents the imaging of choice in follow-up of patients with high serum Tg and negative 131 I-WBS but in the last decades the research has focused on finding “second generation” radiopharmaceuticals for PET imaging, with both diagnostic and prognostic purposes, aiming to change the way to image thyroid cancer. Moreover, the use of various PET radiopharmaceuticals, that offer the possibility to explore different pathways involved in thyroid cancer, could find important applications in the near future for clinical decision making in order to program tailored treatments and follow-up. It would be desirable to use the same radiopharmaceutical for both imaging and dosimetric purpose to achieve a tailored therapy. Many efforts are focused in this direction and 124 I-PET/CT is now emerging as a valid tool in restaging and therapy management of DTC with promising results. Although the preliminary data available in literature require a confirmation in larger studies with longer follow-up, we think that in next future 124 -PET/CT could gain an important role for management of DTC. The aim of this review was to perform a systematic analysis of literature describing the state of art of “second generation” PET-radiopharmaceuticals for imaging DTC. Discussion is focused on the utility of 124 I

Radiochemical syntheses further radiopharmaceuticals for positron emission tomography and new strategies for their production

CERN Document Server

Kilbourn, Michael R; Kilbourn, Michael R

2015-01-01

This book describes methods and procedures for preparing PET radiopharmaceuticals, and highlights new methods for conducting radiochemical reactions with carbon-11 (C11) and fluorine-18 (F18), which are two of the most commonly used radionuclides in positron emission tomography (PET) imaging.     Provides reliable methods for radiochemical syntheses and reactions, including all essential information to duplicate the procedure     Eliminates the time-consuming process of searching journal articles and extracting pertinent details from lengthy experimental sections or supporting information     Focuses on an emerging and important area for pharmaceutical and medical applications     Encompasses technical, regulatory, and application aspects     Includes solid-phase radiochemistry, transition-metal catalyzed radiochemistry, microfluidics, click chemistry, green radiochemistry and new strategies for radiopharmaceutical quality control.

Labeling of complex molecules with 18F, 13N, and 11C. Progress report, March 1, 1981-February 28, 1982

International Nuclear Information System (INIS)

Brownell, G.L.; Elmaleh, D.R.

1981-09-01

The overall objective during the period covered by this report was to develop a broad spectrum of radiopharmaceuticals labeled with short-lived cyclotron produced positron emitters, 11 C, 13 N and 18 F. The progress report of this year will summarize work done in the last three years. The goals of the program during the last three years were: to build and complete the transport system to Nuclear Medicine; to complete the modular automated system for important precursor production: formaldehyde, methyliodide, cyanide; to perform animal studies with the 18 F-glucose analogs 2FDG and 3FDG and measure the rate constants and glucose metabolic rates derived from the Sokoloff model for both agents in different animal species; to initiate the development of new fatty acid analogs for myocardial imaging and metabolism; and to develop syntheses for 18 F and 11 C sugar analogs

On the synthesis of radiofluorinated amino acids by isotope exchange based on the example of 6-[18F]Fluor-L-DOPA

International Nuclear Information System (INIS)

Wagner, F.M.

2008-06-01

In nuclear medical diagnosis, 6-[ 18 F]fluoro-L-3,4-dihydroxyphenylalanine (6-[ 18 F]fluoro-LDOPA), an analogue of L-DOPA, is one of the few established radiopharmaceuticals used for the in vivo investigation of the presynaptic dopaminergic metabolism and of some kind of tumours via Positron Emission Tomography (PET). The presently used method of preparation of the radiotracer by electrophilic labelling is limited to low amounts of activity at high costs. Known nucleophilic syntheses, however, result either in insufficient enantiomeric purity or the known multi-step syntheses are hard to automate, due to their complexity. During this work a novel, easy to automate alternative for the preparation of 6-[ 18 F]fluoro-L-DOPA, was developed and evaluated, using a direct nucleophilic 18 F-fluorination of a protected amino acid derivative. The resulting product has a very high enantiomeric purity. At first, the general suitability of the (S)-BOC-BMI-derivatives for the synthesis of 18 F-labelled amino acids, used in this work, was investigated using a less complex precursor, which resulted in the amino acid 6-[ 18 F]fluoro-L-m-tyrosin via acidic hydrolysis. The preparation of a useful precursor for the nucleophilic 18 F-isotope substitution, namely the (2S,5S)-tert.-butyl- 5-(2-fluoro-5-formylbenzyl)-2-tert. -butyl-3-methyl-4-oxoimidazolidine-1-carbox= yl ate, was investigated in three general different ways. At first it was tried to obtain this product via formylation after coupling with the BOC-BMI, secondly via α,β-dehydro amino acid derivatives and finally via a systematic multi-step synthesis. Only the last mentioned way resulted in a precursor with sufficient purity that could be labelled. The radiochemical yield of the isotopic exchange was about 60 %. In the next step, the presented concept was modified to synthesize a precursor for the preparation of 6-[ 18 F]fluoro-L-DOPA. Only a combination of the protecting groups benzyl and THP resulted in the useful

Effect of the prosthetic group on the pharmacologic properties of 18F-labeled rhodamine B, a potential myocardial perfusion agent for positron emission tomography (PET).

Science.gov (United States)

Bartholomä, Mark D; Gottumukkala, Vijay; Zhang, Shaohui; Baker, Amanda; Dunning, Patricia; Fahey, Frederic H; Treves, S Ted; Packard, Alan B

2012-12-27

We recently reported the development of the 2-[(18)F]fluoroethyl ester of rhodamine B as a potential positron emission tomography (PET) tracer for myocardial perfusion imaging. This compound, which was prepared using a [(18)F]fluoroethyl prosthetic group, has significant uptake in the myocardium in rats but also demonstrates relatively high liver uptake and is rapidly hydrolyzed in vivo in mice. We have now prepared (18)F-labeled rhodamine B using three additional prosthetic groups (propyl, diethylene glycol, and triethylene glycol) and found that the prosthetic group has a significant effect on the in vitro and in vivo properties of these compounds. Of the esters prepared to date, the diethylene glycol ester is superior in terms of in vitro stability and pharmacokinetics. These observations suggest that the prosthetic group plays a significant role in determining the pharmacological properties of (18)F-labeled compounds. They also support the value of continued investigation of (18)F-labeled rhodamines as PET radiopharmaceuticals for myocardial perfusion imaging.

PET/CT studies of multiple myeloma using {sup 18}F-FDG and {sup 18}F-NaF: comparison of distribution patterns and tracers' pharmacokinetics

Energy Technology Data Exchange (ETDEWEB)

Sachpekidis, Christos [Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg (Germany); German Cancer Research Center, Medical PET Group - Biological Imaging Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Goldschmidt, Hartmut; Hose, Dirk [University of Heidelberg, Medical Clinic V, Heidelberg (Germany); National Center for Tumor Diseases Heidelberg, Heidelberg (Germany); Pan, Leyun; Cheng, Caixia; Dimitrakopoulou-Strauss, Antonia [Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg (Germany); Kopka, Klaus [German Cancer Research Center, Division of Radiopharmaceutical Chemistry, Heidelberg (Germany); Haberkorn, Uwe [Clinical Cooperation Unit Nuclear Medicine, German Cancer Research Center, Heidelberg (Germany); University of Heidelberg, Division of Nuclear Medicine, Heidelberg (Germany)

2014-07-15

The aim of this prospective study is to evaluate the combined use of fluorine-18 fluorodeoxyglucose ({sup 18}F-FDG) and fluorine-18 sodium fluoride ({sup 18}F-NaF) PET/CT in the skeletal assessment of patients with multiple myeloma (MM) and to compare the efficacy of these two PET tracers regarding detection of myeloma-indicative osseous lesions. The study includes 60 patients with multiple myeloma (MM) diagnosed according to standard criteria. All patients underwent dynamic (dPET/CT) scanning of the pelvis as well as whole body PET/CT studies with both tracers. The interval between the two exams was one day. Sites of focal increased {sup 18}F-FDG uptake were considered as highly suspicious of myelomatous involvement. The lesions detected on the {sup 18}F-NaF PET/CT scans were then correlated with those detected on {sup 18}F-FDG PET/CT, which served as a reference. Moreover, the {sup 18}F-FDG PET/CT results were also correlated with the low-dose CT findings. The evaluation of dPET/CT studies was based on qualitative evaluation, SUV calculation, and quantitative analysis based on a 2-tissue compartment model and a non-compartmental approach. Whole body {sup 18}F-FDG PET/CT revealed approximately 343 focal lesions while {sup 18}F-NaF PET/CT revealed 135 MM-indicative lesions (39 % correlation). CT demonstrated 150 lesions that correlated with those in {sup 18}F-FDG PET/CT (44 % correlation). Six patients demonstrated a diffuse pattern of disease with {sup 18}F-FDG, while 15 of them had a mixed (diffuse and focal) pattern of skeletal {sup 18}F-FDG uptake. A high number of degenerative, traumatic and arthritic disease lesions were detected with {sup 18}F-NaF PET/CT. In three patients with multiple focal {sup 18}F-FDG-uptake, {sup 18}F-NaF PET/CT failed to demonstrate any bone lesion. The dPET/CT scanning of the pelvic area with {sup 18}F-FDG and {sup 18}F-NaF revealed 77 and 24 MM-indicative lesions, respectively. Kinetic analysis of {sup 18}F-FDG revealed the

Development of O-18 stable isotope separation technology using membrane

Energy Technology Data Exchange (ETDEWEB)

Kim, Jae Woo; Kim, Taek Soo; Choi, Hwa Rim; Park, Sung Hee; Lee, Ki Tae; Chang, Dae Shik

2006-06-15

The ultimate goal of this investigation is to develop the separation technology for O-18 oxygen stable isotope used in a cyclotron as a target for production of radioisotope F-18. F-18 is a base material for synthesis of [F-18]FDG radio-pharmaceutical, which is one of the most important tumor diagnostic agent used in PET (Positron Emission Tomography). More specifically, this investigation is focused on three categories as follow, 1) development of the membrane distillation isotope separation process to re-enrich O-18 stable isotope whose isotopic concentration is reduced after used in a cyclotron, 2) development of organic impurity purification technology to remove acetone, methanol, ethanol, and acetonitrile contained in a used cyclotron O-18 enriched target water, and 3) development of a laser absorption spectroscopic system for analyzing oxygen isotopic concentration in water.

Comparison of {sup 18}F-FET and {sup 18}F-FDG PET in brain tumors

Energy Technology Data Exchange (ETDEWEB)

Pauleit, Dirk; Stoffels, Gabriele [Institute of Neuroscience and Medicine, Forschungszentrum Juelich, D-52425 Juelich (Germany); Bachofner, Ansgar [Clinic of Nuclear Medicine, Heinrich-Heine-University, D-40001 Duesseldorf (Germany); Floeth, Frank W.; Sabel, Michael [Department of Neurosurgery, Heinrich-Heine-University, D-40001 Duesseldorf (Germany); Herzog, Hans; Tellmann, Lutz [Institute of Neuroscience and Medicine, Forschungszentrum Juelich, D-52425 Juelich (Germany); Jansen, Paul [Institute of Advanced Simulation, Forschungszentrum Juelich, D-52425 Juelich (Germany); Reifenberger, Guido [Department of Neuropathology, Heinrich-Heine-University, D-40001 Duesseldorf (Germany); Hamacher, Kurt; Coenen, Heinz H. [Institute of Neuroscience and Medicine, Forschungszentrum Juelich, D-52425 Juelich (Germany); Langen, Karl-Josef [Institute of Neuroscience and Medicine, Forschungszentrum Juelich, D-52425 Juelich (Germany)], E-mail: k.j.langen@fz-juelich.de

2009-10-15

The purpose of this study was to compare the diagnostic value of positron emission tomography (PET) using [{sup 18}F]-fluorodeoxyglucose ({sup 18}F-FDG) and O-(2-[{sup 18}F]fluoroethyl)-L-tyrosine ({sup 18}F-FET) in patients with brain lesions suspicious of cerebral gliomas. Methods: Fifty-two patients with suspicion of cerebral glioma were included in this study. From 30 to 50 min after injection of 180 MBq {sup 18}F-FET, a first PET scan ({sup 18}F-FET scan) was performed. Thereafter, 240 MBq {sup 18}F-FDG was injected and a second PET scan was acquired from 30 to 60 min after the second injection ({sup 18}F-FET/{sup 18}F-FDG scan). The cerebral accumulation of {sup 18}F-FDG was calculated by decay corrected subtraction of the {sup 18}F-FET scan from the {sup 18}F-FET/{sup 18}F-FDG scan. Tracer uptake was evaluated by visual scoring and by lesion-to-background (L/B) ratios. The imaging results were compared with the histological results and prognosis. Results: Histology revealed 24 low-grade gliomas (LGG) of World Health Organization (WHO) Grade II and 19 high-grade gliomas (HGG) of WHO Grade III or IV, as well as nine others, mainly benign histologies. The gliomas showed increased {sup 18}F-FET uptake (>normal brain) in 86% and increased {sup 18}F-FDG uptake (>white matter) in 35%. {sup 18}F-FET PET provided diagnostically useful delineation of tumor extent while this was impractical with {sup 18}F-FDG due to high tracer uptake in the gray matter. A local maximum in the tumor area for biopsy guidance could be identified with {sup 18}F-FET in 76% and with {sup 18}F-FDG in 28%. The L/B ratios showed significant differences between LGG and HGG for both tracers but considerable overlap so that reliable preoperative grading was not possible. A significant correlation of tracer uptake with overall survival was found with {sup 18}F-FDG only. In some benign lesions like abscesses, increased uptake was observed for both tracers indicating a limited specificity of both

18F-fluorination by crown ether-metal fluoride

International Nuclear Information System (INIS)

Irie, T.; Fukushi, K.; Ido, T.; Kasida, Y.; Nozaki, T.

1982-01-01

18 F-Fluorination by ''naked'' 18 F - anion produced by complexing anhydrous K 18 F, which was prepared from aqueous 18 F, with 18 -Crown-6 was described for preparing 18 F-21-fluoroprogesterone. In order to find out optimum conditions in this labelling method, various factors were investigated such as the solubility of KF in organic solvents containing 18 -Crown-6 and its reactivity for the nucleophilic displacement of 21-mesylate of progesterone. Chloroform was a good solvent in solubilization of KF and its reactivity. Problems in this labelling procedure were also examined, such as a supporter for transferring the labelled anhydrous K 18 F and reaction vessels. Use of a Teflon reaction vessel resulted in a good radiochemical yield based on the starting activity of $ 18 water. (author)

In vitro study of tumor seeking radiopharmaceutical uptake by human breast cancer cell line MCF-7 after paclitaxel treatment

International Nuclear Information System (INIS)

Choi, Joon Young; Choi, Yong; Choe, Yearn Seong; Lee, Kyung Han; Kim, Byung Tae

2007-01-01

This study was designed to investigate the cellular uptake of various tumor imaging radiopharmaceuticals in human breast cancer cells before and after paclitaxel exposure considering viable cell number. F-18-fluorodeoxyglucose, C-11-methionine. TI-201, Tc-99m-MIBI, and Tc-99m-tetrofosmin were used to evaluate the cellular uptake in MCF-7 cells. MCF-7 cells were cultured in multi-well plates. Wells were divided into DMSO exposure control group, and paclitaxel exposure group. The exposure durations of paclitaxel with 10 nM or 100 nM were 2 h, 6 h, 12 h, 24 h, and 48 h. Viable cell fraction was reduced as the concentration and exposure time of paclitaxel increased. After 10 nM paclitaxel exposure, the cellular uptake of all 5 radiopharmaceuticals was not reduced significantly, irrespective of exposure time and viable cell fraction. After 100 nM paclitaxel exposure, the cellular uptake of all 5 radiopharmaceuticals was enhanced significantly irrespective of viable cell fraction. The peak uptake was observed in experimental groups with paclitaxel exposure for 6 to 48 h according the type of radiopharmaceutical. When the cellular uptake was adjusted for the viable cell fraction and cell count, the peak cellular uptake was observed in experimental groups with paclitaxel exposure for 48 h, irrespective of the type of radiopharmaceutical. The cellular uptake of F-18-fluorodeoxyglucose, C-11-methionine, TI-201, Tc-99m-MIBI, and Tc-99m-tetrofosmin did not reflect viable cell number in MCF-7 cells after paclitaxel exposure for up to 48 h

Radiosynthesis of [18F]FEt-Tyr-urea-Glu ([18F]FEtTUG) as a new PSMA ligand

International Nuclear Information System (INIS)

Al-Momani, E.; Malik, N.; Machulla, H.J.; Reske, S.N.; Solbach, C.

2013-01-01

An efficient radiosynthesis of [ 18 F]FEt-Tyr-urea-Glu ([ 18 F]FEtTUG) as a new ligand for prostate specific membrane antigen (PSMA) was developed by use of [ 18 F]fluoroethyltosylate as labeling precursor. The corresponding fluoroethyl-tyrosine-urea-glutamate peptide was prepared as reference standard for HPLC control and identified and characterized by standard procedures (MS, NMR). The labeling conditions were optimized with respect to reaction time, reaction temperature, base and solvent. The maximal radiochemical yield of [ 18 F]FEtTUG (77 ± 0.8 %) was obtained within a reaction time of 15 min at a reaction temperature of 80 deg C using 10 M NaOH (18 equiv. related to precursor) in 80 % aqueous acetonitrile. The total preparation time including radiosynthesis, hydrolysis, HPLC purification and formulation was 70 min (EOB). The radiochemical purity was ≥98 %. (author)

Characterization of membrane potential-dependent uptake of the novel PET tracer 18F-fluorobenzyl triphenylphosphonium cation

International Nuclear Information System (INIS)

Madar, Igal; Ravert, Hayden; Abro, Masroor; Pomper, Martin; Dannals, Robert; Frost, James J.; Nelkin, Barry

2007-01-01

Mitochondrial dysfunction has been attributed a critical role in the etiology and pathogenesis of numerous diseases, and is manifested by alterations of the organelle's membrane potential (Δψ m ). This suggests that Δψ m measurement can be highly useful for diagnostic purposes. In the current study, we characterized the capability of the novel PET agent 18 F-fluorobenzyl triphenylphosphonium ( 18 F-FBnTP) to assess Δψ m , compared with the well-established voltage sensor 3 H-tetraphenylphosphonium ( 3 H-TPP). 18 F-FBnTP and 3 H-TPP uptake under conditions known to alter Δψ m and plasma membrane potential (Δψ p ) was assayed in the H345 lung carcinoma cell line. 18 F-FBnTP biodistribution was assessed in CD1 mice using dynamic PET and ex vivo gamma well counting. 18 F-FBnTP and 3 H-TPP demonstrated similar uptake kinetics and plateau concentrations in H345 cells. Stepwise membrane depolarization resulted in a linear decrease in 18 F-FBnTP cellular uptake, with a slope (-0.58±0.06) and correlation coefficient (0.94±0.07) similar (p>0.17) to those measured for 3 H-TPP (-0.63±0.06 and 0.96±0.05, respectively). Selective collapse of Δψ m caused a substantial decrease in cellular uptake for 18 F-FBnTP (81.6±8.1%) and 3 H-TPP (85.4±6.7%), compared with control. Exposure to the proapoptotic staurosporine, known to collapse Δψ m , resulted in a decrease of 68.7±10.1% and 71.5±8.4% in 18 F-FBnTP and 3 H-TPP cellular uptake, respectively. 18 F-FBnTP accumulated mainly in kidney, heart and liver. 18 F-FBnTP is a mitochondria-targeting PET radiopharmaceutical responsive to alterations in membrane potential with voltage-dependent performance similar to that of 3 H-TPP. 18 F-FBnTP is a promising new voltage sensor for detection of physiological and pathological processes associated with mitochondrial dysfunction, such as apoptosis, using PET. (orig.)

Development of methodologies for internal exposure assessment due to the radiopharmaceutical {sup 18}FDG; Desenvolvimento de metodologias para avaliacao da exposicao ocupational interna devido ao radiofarmaco {sup 18}FDG

Energy Technology Data Exchange (ETDEWEB)

Lacerda, Isabelle Viviane Batista de

2013-07-01

The production of {sup 18}F has increased in the last decade. It is produced basically for the synthesis of {sup 18}F- fluorodeoxyglucose ({sup 18}FDG), the main radiopharmaceutical used in PET (Positron Emission Tomography) scans. The growth in the frequency of these tests resulted in rise of the number of occupationally exposed individuals (OEI) to the radionuclide {sup 18}F as {sup 18}FDG, increasing thereby the probability of its accidental incorporation. This study aimed to implement optimized techniques for assessing internal exposures of individuals occupationally exposed through both in vivo and in vitro bioassay methods during production and handling of {sup 18}FDG at the Divisao de Producao de Radiofarmacos (DIPRA), Centro Regional de Ciencias Nucleares do Nordeste (CRCN-NE/CNEN). The in vivo monitoring was conducted at the Laboratorio de Dosimetria Interna, Divisao de Laboratorios Tecnico-Cientificos (DILAB). For this bioassay method, measurements were done with a 3x3' NaI(Tl) scintillation detector coupled to Genie 2000 software. The calibration of the system was performed with a brain phantom containing a standard liquid source of {sup 22}Na to simulate a contaminated individual. The calibration of the HPGe coaxial detector for in vitro monitoring was performed at the Laboratorio de Medidas de Atividade de Radionuclideos (DIPRA/CRCN-NE/CNEN) with a standard source of {sup 22}Na. Base on the calibration factors, it was possible to determine the minimum detectable activities (MDA) for the systems by using direct measurements and simulation of uncontaminated urine. Then, through the biokinetic models published by ICRP 106 and edited by the AIDE software (version 6.0), it was possible to estimate the minimum detectable effective dose (MDED), which evaluates the detection sensitivity of the techniques developed. The MDED was estimated for in vivo and in vitro measurements performed 2.4 hours after the occurrence of incorporation by ingestion, since

Demand of radiopharmaceutical Fluoride 18-FDG (fluorodeoxyglucose) in the Sao Paulo State metropolitan area

International Nuclear Information System (INIS)

Sato, Renato C.; Zouain, Desiree M.

2005-01-01

This research presents partial results from the development of a Masters Dissertation for the Post-Graduation in Nuclear Technology Program - IPEN/USP, aiming to study the demand of radiopharmaceutical Fluoride 18-FDG (fluorodeoxyglucose) in the Sao Paulo State metropolitan area, as a subsidiary for the establishment of distribution strategy within the State. This study presented the results of a bibliographic review as well as the market evolution for FDG in Sao Paulo. Studies pointed to a tendency of an increase in the international and national nuclear medicine market; while the United States of America participate in 47% of the world profit, South America shares only 2.5% of the global market. This market will tend to grow in 2006 to 2020 up to 776% for diagnosis and 760% for therapy. Partial results are presented in this study from researching medical centers that use PET in the city of Sao Paulo, as well as companies that commercialize the equipment and the manufacturer center. There is an increase of sales for IPEN's Fluoride 18-FDG and its representation on the total radiopharmaceutical profit surpassed 5.3% in 2003 to 8.2% in 2004. The dissemination of this technology in Brazil is lately being discussed especially due to the acquisition price of the equipment as well as the viability of the resources (Fluoride 18- FDG; implementation strategies of regional cyclotron accelerators) and the question of remuneration of the PET produced exams for health care plans and national health care system (SUS). IPEN is developing yet another study to grasp possible demand for this product in the Southern and Southeastern regions, allowing better view of the necessity of the supplement, and in study the implementation of a new cyclotron in the institute dedicated for the production of Fluoride 18-FDG. (author)

Synthesis and evaluation of [[sup 18]F]fluoroprogestins and [[sup 18]F]fluorometoprolol

Energy Technology Data Exchange (ETDEWEB)

De Groot, T J

1993-05-01

The author investigated if specific radioactively labelled compounds could be applied to gain insight into particular psychic diseases, f.e. Parkinson's disease and schizophrenia, by means of Positron Emission Tomography (PET). No appropriate compounds were found. In this thesis the syntheses of fluorine-18 labelled progestins and [beta][sub 1]-adrenergic ligands are described. Three approaches towards [[sup 18]F]fluorination are investigated. The first method concerns direct S[sub N]2-substitution, the second approach is the opening of an epoxide, and the third approach is [[sup 18]F]fluoroalkylation. The positron emitting radionuclide fluorine-18 was used because of its relatively long decay time and the possibility to produce it in high yields and with high specific activity. The target systems which were applied for the production of fluorine-18 are described in chapter two. Important chemical and physical aspects of [[sup 18]F]fluoride are reviewed in the same chapter. In chapter three the synthesis of 21-[[sup 18]F]fluorinated progestins is discussed. The synthesis of four 21-[[sup 18]F]fluoroprogesterone derivatives is described and the results of an in vivo evaluation of two of these ligands are discussed. Possible routes leading to 6[alpha]-[[sup 18]F]fluoroprogestins are presented in chapter four. The radiochemical approaches towards the synthesis of these ligands are discussed. In chapter five the proposed routes to the fluorine-18 labelled [beta][sub 1]-adrenergic ligands are described and evaluated in the synthesis of two model compounds. 1-[[sup 18]F]fluorometoprolol, the [[sup 18]F]fluorinated analogue of a potent beta-blocker, is prepared using one of the investigated methods. The biological effect of fluorine substitution of a [beta][sub 1]-adrenergic ligand is discussed on the basis of an in vitro and in vivo evaluation. 21 figs., 28 schemes, 19 tabs., 182 refs.

Carrier-added and no-carrier-added syntheses of [18F]spiroperidol and [18F]haloperidol

International Nuclear Information System (INIS)

Kilbourn, M.R.; Welch, M.J.; Dence, C.S.; Tewson, T.J.; Saji, H.; Maeda, M.

1984-01-01

Syntheses of [ 18 F]haloperidol and [ 18 F]spiroperidol in both no-carrier-added and carrier-added forms have been accomplished. The no-carrier-added [ 18 F]butyrophenone neuroleptics were prepared in low ( 18 F-neuroleptics were prepared in better (5-17%) yields by 18 F-for- 19 F nucleophilic aromatic substitution. The preparation of all synthetic precursors, and procedures for radiolabeling are fully described. (author)

Evaluation of steam sterilization conditions for [{sup 18}F]fludeoxyglucose

Energy Technology Data Exchange (ETDEWEB)

Santos, Priscilla F.; Nascimento, Leonardo T.; Valente, Eduardo S.; Silva, Juliana B.; Silveira, Marina B.; Ferreira, Soraya Z., E-mail: somafe@cdtn.b [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil). Unidade de Pesquisa e Producao de Radiofarmacos

2011-07-01

[{sup 18}F]Flu deoxyglucose ({sup 18}FDG) is the most commonly used radiopharmaceutical for positron emission tomography. Sterile filtration of the final product into sterile vials using 0.22 {mu}m filter membrane is usually adopted for {sup 18}FDG. However, Good Manufacturing Practice (GMP) guidelines recommend heat sterilization as the method of choice to ensure sterility of pharmaceutical preparations. The aim of this study was to essay different steam sterilization conditions in order to choose the best one for {sup 18}FDG. Three different sterilization conditions were essayed. The first one at 121 deg C for 15 minutes, the second one at 135 deg C for 3.5 minutes and the third one at 133 deg C for 2 minutes. {sup 18}FDG pH-formulation was kept around 6.0. At the end of autoclave cycles, {sup 18}FDG sterility was evaluated by direct inoculation of {sup 18}FDG in culture media and radiochemical purity was determined by TLC and HPLC. Results demonstrated that all essayed conditions were able to ensure {sup 18}FDG sterility, but caused a decrease in radiochemical purity of {sup 18}FDG. Autoclave cycle at 133 deg C for 2 minutes was the best essayed condition for {sup 18}FDG terminal sterilization, once it provided the greater radiochemical purity value and took less time. {sup 18}FDG was able to meet specifications after autoclave cycles, what supports the application of steam sterilization in routine {sup 18}FDG production, in compliance with GMP. (author)

Treatment response evaluation with 18F-FDG PET/CT and 18F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation.

Science.gov (United States)

Sachpekidis, Christos; Hillengass, J; Goldschmidt, H; Wagner, B; Haberkorn, U; Kopka, K; Dimitrakopoulou-Strauss, A

2017-01-01

The aim of this study was to assess the combined use of the radiotracers 18 F-FDG and 18 F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT). Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with 18 F-FDG and 18 F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD). An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, 18 F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, 18 F-FDG PET/CT-based treatment response revealed CR in 14 patients ( 18 F-FDG PET/CT CR), PR in 11 patients ( 18 F-FDG PET/CT PR) and progressive disease in four patients ( 18 F-FDG PET/CT PD). In terms of 18 F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, 18 F-NaF PET/CT depicted 56 of the 129 18 F-FDG positive lesions (43 %). Follow-up 18 F-NaF PET/CT showed persistence of 81.5 % of the baseline 18 F-NaF positive MM lesions after treatment, despite the fact that 64

FDOPA-(18F: a PET radiopharmaceutical recently registered for diagnostic use in countries of the European Union

Directory of Open Access Journals (Sweden)

Yanna-Marina Chevalme

2007-09-01

Full Text Available Positron emission tomography (PET and its recent update PET/CT are very effective diagnostic tools for non-invasive imaging of metabolic or functional disorders in target tissues. The clinical usefulness of fluorodeoxyglucose-(18F (FDG has been now widely accepted. Recently, the clinical usefulness of fluoroDOPA-(18F or FDOPA, an aminoacid labelled with the same positron emitter fluorine-18, has been evaluated and recognised in France and subsequently in several EU countries. FDOPA is diagnostic PET agent, which has been used for decades in imaging the loss of dopaminergic neurons in Parkinson's disease, and more recently to detect, stage and restage neuroendocrine tumours and to search for recurrence of viable glioma tissue. The present article summarises the body of evidence that led the French Medicines Agency (AFSSAPS to grant a marketing authorisation to IASOdopa, a commercial preparation of FDOPA. Brief case reports and figures illustrate the diagnostic performance of FDOPA PET or PET/CT in the different settings that are currently approved in oncology.Tomografia por emissão de positrons (PET e sua recente atualização PET/CT são ferramentas de diagnóstico muito eficientes para imagens não invasivas de desordens metabólicas ou funcionais em tecido alvo. A utilidade clínica da fluordesoxiglicose-(18F(FDG tem sido agora largamente aceita. Recentemente, a utilidade clinica de fluoroDOPA-(18F ou FDOPA, um aminoácido marcado com o mesmo emissor de pósitron, flúor-18, tem sido avaliado e reconhecido na França e subsequentemente em alguns países da União Européia. FDOPA é o radiofármaco para diagnóstico em PET, o qual tem sido usado por décadas para obtenção de imagens da perda de neurônios dopaminérgicos na doença de Parkinson e, mais recentemente, para identificar inicialmente o estágio e a reavaliação de tumores neuroendócrinos e para a pesquisa da recorrência de glioma viável. O presente artigo resume o conjunto

Synthesis of 2-deoxy-2-[18F]-fluoro-β-mannosyl [18F]-fluoride as a potential imaging probe for glycosidases

International Nuclear Information System (INIS)

McCarter, J.D.; Withers, S.G.; Adam, M.J.

1992-01-01

The mechanism-based glycosidase inhibitor 2-deoxy-2-[ 18 F]-fluoro-Β-mannosyl 2-[ 18 F]-fluoride was synthesized and its covalent binding to Agrobacterium Β-glucosidase was demonstrated in vitro. (Author)

18F-FDG PET/CT in breast cancer: Evidence-based recommendations in initial staging.

Science.gov (United States)

Caresia Aroztegui, Ana Paula; García Vicente, Ana María; Alvarez Ruiz, Soledad; Delgado Bolton, Roberto Carlos; Orcajo Rincon, Javier; Garcia Garzon, Jose Ramon; de Arcocha Torres, Maria; Garcia-Velloso, Maria Jose

2017-10-01

Current guidelines do not systematically recommend 18F-FDG PET/CT for breast cancer staging; and the recommendations and level of evidence supporting its use in different groups of patients vary among guidelines. This review summarizes the evidence about the role of 18F-FDG PET/CT in breast cancer staging and the therapeutic and prognostic impact accumulated in the last decade. Other related aspects, such as the association of metabolic information with biology and prognosis are considered and evidence-based recommendations for the use of 18F-FDG PET/CT in breast cancer staging are offered. We systematically searched MEDLINE for articles reporting studies with at least 30 patients related to clinical questions following the Problem/Population, Intervention, Comparison, and Outcome framework. We critically reviewed the selected articles and elaborated evidence tables structuring the summarized information into methodology, results, and limitations. The level of evidence and the grades of recommendation for the use of 18F-FDG PET/CT in different contexts are summarized. Level III evidence supports the use of 18F-FDG PET/CT for initial staging in patients with recently diagnosed breast cancer; the diagnostic and therapeutic impact of the 18F-FDG PET/CT findings is sufficient for a weak recommendation in this population. In patients with locally advanced breast cancer, level II evidence supports the use of 18F-FDG PET/CT for initial staging; the diagnostic and therapeutic impact of the 18F-FDG PET/CT findings is sufficient for a strong recommendation in this population. In patients with recently diagnosed breast cancer, the metabolic information from baseline 18F-FDG PET/CT is associated with tumor biology and has prognostic implications, supported by level II evidence. In conclusion, 18F-FDG PET/CT is not recommended for staging all patients with early breast cancer, although evidence of improved regional and systemic staging supports its use in locally advanced

Activity-based costing evaluation of a [(18)F]-fludeoxyglucose positron emission tomography study.

Science.gov (United States)

Krug, Bruno; Van Zanten, Annie; Pirson, Anne-Sophie; Crott, Ralph; Borght, Thierry Vander

2009-10-01

The aim of the study is to use the activity-based costing approach to give a better insight in the actual cost structure of a positron emission tomography procedure (FDG-PET) by defining the constituting components and by simulating the impact of possible resource or practice changes. The cost data were obtained from the hospital administration, personnel and vendor interviews as well as from structured questionnaires. A process map separates the process in 16 patient- and non-patient-related activities, to which the detailed cost data are related. One-way sensitivity analyses shows to which degree of uncertainty the different parameters affect the individual cost and evaluate the impact of possible resource or practice changes like the acquisition of a hybrid PET/CT device, the patient throughput or the sales price of a 370MBq (18)F-FDG patient dose. The PET centre spends 73% of time in clinical activities and the resting time after injection of the tracer (42%) is the single largest departmental cost element. The tracer cost and the operational time have the most influence on cost per procedure. The analysis shows a total cost per FDG-PET ranging from 859 Euro for a BGO PET camera to 1142 Euro for a 16 slices PET-CT system, with a distribution of the resource costs in decreasing order: materials (44%), equipment (24%), wage (16%), space (6%) and hospital overhead (10%). The cost of FDG-PET is mainly influenced by the cost of the radiopharmaceutical. Therefore, the latter rather than the operational time should be reduced in order to improve its cost-effectiveness.

MCNPX dosimetry and radiation-induced cancer risk estimation from {sup 18}F-FDG pediatric PET at Brazilian population

Energy Technology Data Exchange (ETDEWEB)

Mendes, Bruno M.; Fonseca, Telma C.F. [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Campos, Tarcisio P.R., E-mail: bmm@cdtn.br, E-mail: tcff@cdtn.br, E-mail: tprcampos@yahoo.com.br [Universidade Federal de Minas Gerais (PCTN/UFMG), Belo Horizonte, MG (Brazil). Programa de Pós-Graduação em Ciências e Técnicas Nucleares

2017-07-01

Positron emission tomography (PET) using {sup 18}F-FDG has increased significantly in pediatric patients. PET with {sup 18}F-FDG has often been applied in oncology. Cancer induction is one of the main stochastic risk from exposure to ionizing radiation of {sup 18}F-FDG. Radiation-induced cancer risk estimation due to medical exposures is an important tool for risk/benefit assessing. The objective was to perform dosimetry and estimate the risk of cancer induction due to pediatric use of {sup 18}F-FDG. MCNPX Computational dosimetry was performed to estimate organ absorbed doses resulting from {sup 18}F-FDG pediatric use. Two voxelized phantoms, kindly provided by the GSF - Helmholtz Zentrum, were used: 'Child' - 7 years child and 'Baby' 8-week-old infant. ICRP-128 publication provided the radiopharmaceutical biodistribution of F-18. Tables containing organ absorbed dose and effective dose per unit of injected activity for the two phantoms were obtained. The injected activities were estimated according to data provided in the literature. Images of the absorbed dose distribution were generated from both models. The BEIR VII methodology was used to calculate the risk of cancer induction. The risk of cancer induction (per imaging procedure) for the seven-year-old child was (0.09% ♂ and 0.15% ♀) and for the eight-week old baby was (0.11% ♂ and 0.21% ♀). The {sup 18}F-FDG absorbed dose distribution in the children and infants showed some divergences in comparison to adult data. Probably, the biokinetic data used to children and infants is the main reason for this disconnection. (author)

Synthesis of 6-[18F] and 4-[18F]fluoro-L-m-tyrosines via regioselective radiofluorodestannylation

International Nuclear Information System (INIS)

Namavari, Mohammad; Satyamurthy, N.; Phelps, M.E.; Barrio, J.R.; California Univ., Los Angeles, CA

1993-01-01

The regioselective radiofluorodestannylation of 6-trimethylstannyl-L-m-tyrosine derivative with [ 18 F]F 2 and [ 18 F]acetyl hypofluorite afforded, after acid hydrolysis, 6-[ 18 F]fluoro-L-m-tyrosine in radiochemical yields of 23 and 17%, respectively. Similarly, 4-[ 18 F]fluoro-L-m-tyrosine was synthesized in 11% radiochemical yield from the corresponding 4-trimethylstannyl-L-m-tyrosine derivative using [ 18 F]F 2 . The structural analyses of precursors, intermediates, and the final products (after 18 F decay), were carried out by 1 H, 13 C, 19 F, 119 Sn-NMR and high resolution mass spectroscopy. (author)

Biodistribution and metabolism of 16α-([/sup 18/F]-fluoro)-17β-estradiol

International Nuclear Information System (INIS)

Mathias, C.J.; Brodack, J.W.; Kilbourn, M.R.; Carlson, K.A.; Katzenellenbogen, J.A.; Welch, M.J.

1985-01-01

The uptake of receptor-mediated radiopharmaceuticals as measured by target to non-target uptake ratios depends upon many parameters. These include blood flow to the tissue, blood volume, receptor concentration as well as metabolism of the tracer. In a rat tumor model (DMBA) induced mammary tumors with high concentration of estrogen receptors) uptake of /sup 18/F-estradiol was studied while blood flow was measured with the use of /sup 125/I-iodoantipyrine, blood volume was measured with the use of /sup 99m/Tc-labeled red blood cells, and the receptor concentration by in vitro assay. The results demonstrate no correlation between blood flow and uptake of ligand, or between receptor concentration and uptake of ligand. No correlation existed between blood volume and uptake or /sup 18/F-estradiol, even though the blood volume varied by a factor of --20 in the tumors studied. The distribution of the fluorine-18 may depend upon metabolites of the ligand rather than the ligand itself. The authors have developed a technique to separate metabolites from the administered compound in blood and tissues. The distribution of the compound in the blood at times >30 mins after injection was primarily within the red blood cells in a chemical form that was not extractable even in lysed blood samples. By injecting blood from one rate into another the authors have shown that the activity in blood 2 hours after injection of /sup 18/F-estradiol is not available for uptake in receptor rich tissue but remains in the blood and non-target tissues

Radiopharmaceuticals

International Nuclear Information System (INIS)

Theobald, A.E.

1989-01-01

This book is a review of the latest developments in radiopharmaceuticals. It covers the development of radiopharmaceutical compounds, the theory and practice of their synthesis, and examples of their application. Also covers safe handling of radiopharmaceuticals, legislation affecting their use, radiation monitoring, radiochromatography, and computer techniques

Biological distribution of reactor produced 18F-FDG. Local experience

International Nuclear Information System (INIS)

Sierralta, M.P.; Massardo, T.; Gil, M.C.; Chandia, M.; Godoy, N.; Troncoso, F.; Jofre, M.J.

2002-01-01

Introduction: Quality control through an animal model that relates bio distribution of a substance is fundamental prior to using it in human beings. For the evaluation of myocardial viability after recent myocardial infarction, the use of reactor produced 18F-FDG (a radiotracer usually obtained in cyclotron) is proposed, production of wish had never been attempted in our country. The aim of the study was to compare the specific activities found in the different tissues after the injection of this reactor produced radiopharmaceutical with those obtained by others authors with cyclotron 18F-FDG. Material WISTAR female white mice, men weight 25,28 +/- 1,09 g (23,8-26,9 range) in standard support conditions was used. 1,22 MBq (33 mCi) of 18F-FDG were injected in a lateral tail vein. Previously anaesthetised with Chloroform, the animals were sacrificed by jugular section at 5, 30 and 60 minutes intervals post injection. Blood and organs were removed (liver, lungs, heart, brain, urine plus bladder, kidneys, femur, muscle and quivers), placed in vials, then weighed, and finally taken to a Gamma Packard Minaxi γ Auto-gamma 5000 serie counter to obtain the counts per minute (cpm) (previously the empty vials were weighed too). At same time, STANDARDS (STD) (3 dilutions) cpm and BACKGROUND (BKG) cpm were collected. We calculate 1) mean BKG cpm, 2) mean STD cpm, who then were corrected by decay factor and dilution, and 3) each one of the tissues cpm, that then were corrected by decay factor, divided by the corresponding dilution cpm and multiplied by 100 to obtain the Injected Activity % (IA%). Finally, the IA% was divided by the tissue weight and get the Specific Activity (SA). Mean and standard deviation for each tissue at the 3 intervals were calculated. Results: The uptake distribution at 30 and 60 minutes were similar between reactor and cyclotron produced 18F-FDG, with significant bigger SA in heart and brain respect of the rest organs. There were significant

Biological distribution of reactor produced 18F-FDG. Local experience

Energy Technology Data Exchange (ETDEWEB)

Sierralta, M P [University of Chile Clinical Hospital Nuclear Medicine Centre, Santiago (Chile); Military Hospital Nuclear Medicine Department, Santiago (Chile); Massardo, T [University of Chile Clinical Hospital Nuclear Medicine Centre, Santiago (Chile); Gil, M C [CGM Nuclear, Santiago (Chile); Chandia, M; Godoy, N; Troncoso, F [CCHEN, CEN La Reina, Santiago (Chile); Jofre, M J [Military Hospital Nuclear Medicine Department, Santiago (Chile)

2002-09-01

Introduction: Quality control through an animal model that relates bio distribution of a substance is fundamental prior to using it in human beings. For the evaluation of myocardial viability after recent myocardial infarction, the use of reactor produced 18F-FDG (a radiotracer usually obtained in cyclotron) is proposed, production of wish had never been attempted in our country. The aim of the study was to compare the specific activities found in the different tissues after the injection of this reactor produced radiopharmaceutical with those obtained by others authors with cyclotron 18F-FDG. Material WISTAR female white mice, men weight 25,28 +/- 1,09 g (23,8-26,9 range) in standard support conditions was used. 1,22 MBq (33 mCi) of 18F-FDG were injected in a lateral tail vein. Previously anaesthetised with Chloroform, the animals were sacrificed by jugular section at 5, 30 and 60 minutes intervals post injection. Blood and organs were removed (liver, lungs, heart, brain, urine plus bladder, kidneys, femur, muscle and quivers), placed in vials, then weighed, and finally taken to a Gamma Packard Minaxi {gamma} Auto-gamma 5000 serie counter to obtain the counts per minute (cpm) (previously the empty vials were weighed too). At same time, STANDARDS (STD) (3 dilutions) cpm and BACKGROUND (BKG) cpm were collected. We calculate 1) mean BKG cpm, 2) mean STD cpm, who then were corrected by decay factor and dilution, and 3) each one of the tissues cpm, that then were corrected by decay factor, divided by the corresponding dilution cpm and multiplied by 100 to obtain the Injected Activity % (IA%). Finally, the IA% was divided by the tissue weight and get the Specific Activity (SA). Mean and standard deviation for each tissue at the 3 intervals were calculated. Results: The uptake distribution at 30 and 60 minutes were similar between reactor and cyclotron produced 18F-FDG, with significant bigger SA in heart and brain respect of the rest organs. There were significant

Export of radiopharmaceuticals and establishment of export base of cyclotron

International Nuclear Information System (INIS)

Jung, Kyungil; Kim, Youngsik

2006-01-01

Sam young Unit ech has seized an opportunity to advance into the radiopharmaceuticals market through successful transfer of radiopharmaceuticals manufacturing technology and medical cyclotron, an original technology in nuclear medicine that is the core of less developed areas in nuclear-related fields. The company has continued to push for research development and establishment of market base through industry-academia-research center cooperation with an aim to complement relatively less developed domestic technology and market than in advanced countries, and is making efforts to establish export base in the overseas market based on stabilized supply in the domestic market. As for radiopharmaceuticals, the company is exporting Tc-99m generator to Vietnam, Thailand and the Philippines and preparing itself to export manufacture facilities for Tc-99m generator to Syria and Kazakhstan. In addition, it plans to export 13Mev Cyclotron that has been commercialized after being developed in the domestic market to the U. S. The company plans to grow up to play a pivotal role in the domestic RT area by conducting proactive business activities with an aim to revitalize the domestic market and further domestic original technologies and products in the global market

Lung radiopharmaceuticals

International Nuclear Information System (INIS)

Gonzalez, B.M.

1994-01-01

Indication or main clinical use of Lung radiopharmaceuticals is presented and clasification of radiopharmaceuticals as ventilation and perfusion studies. Perfusion radiopharmaceuticals, main controls for administration quality acceptance. Clearence after blood administration and main clinical applications. Ventilation radiopharmaceuticals, gases and aerosols, characteristics of a ideal radioaerosol, techniques of good inhalation procedure, clinical applications. Comparison of several radiopharmaceuticals reflering to retention time as 50% administered dose, percent administered dose at 6 hours post inhalation, blood activity at 30 and 60 minutes post inhalation, initial lung absorbed dose, cumulated activity.Kinetic description of two radiopharmaceuticals, 99mTcDTPA and 99mTc-PYP

Brain {sup 18}F-FDG PET-MRI co registration: iconographic essay;PET-RM neurologico com FDG-{sup 18}F: ensaio iconografico

Energy Technology Data Exchange (ETDEWEB)

Cavalcanti Filho, Jose Leite Gondim; Machado Neto, Luiz de Souza, E-mail: leite_jose@yahoo.co [Multi Imagem PET, Rio de Janeiro, RJ (Brazil); Fonseca, Lea Mirian Barbosa da; Gasparetto, Emerson Leandro [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil); Domingues, Romeu Cortes; Domingues, Roberto Cortes [Clinica de Diagnostico por Imagem (CDPI), Rio de Janeiro, RJ (Brazil)

2010-05-15

The combination of positron emission tomography (PET) with magnetic resonance imaging (MRI) has been the subject of several studies in recent years. Positron emission tomography is the most sensitive and specific imaging modality in the detection of metabolic changes, but presents limited spatial resolution. On the other hand, MRI presents a significant spatial resolution, besides evaluating soft tissues signal intensity with excellent contrast resolution. The present iconographic essay is aimed at demonstrating the potential clinical application of PET/MRI co registration. The studies were performed in a dedicated PET unit with {sup 18}F-fluorodeoxyglucose (FDG) as radiopharmaceutical and co registered with 1.5 T or 3 T brain MRI. The brain images fusion software presents an already well-established accuracy, so a significant synergy between a functional PET study and an excellent MRI anatomical detail is achieved. The most attractive clinical applications of this approach are the following: epileptogenic zone assessment in patients refractory to drug therapy, identification of patients with cognitive impairment at higher risk for progression to dementia and differentiation of dementias and Parkinsonian syndromes. (author)

Rise of the machines : cyclotrons and radiopharmaceuticals in the PET-CT-MR golden age

International Nuclear Information System (INIS)

Price, Roger

2011-01-01

transforming neuroendocrine tumour imaging. In turn, generator cost-effectiveness (including 99mTc) demands advances in nuclear +/- accelerator technologies. 'Benchtop' petawatt laser-based [18F] production and fluidic-microchip [18F]FDG syntheses, hinting at future cheap 'personalised' production, remain orders-of-magnitude distant. PET benefit/cost can only be improved by combination of demythologising/industrialising radiopharmaceuticals production, diagnostic-quality simultaneous multi-modality imaging (feasible with PET/MR), plus relentless pursuit of economies-of-scale.

Synthesis of O-(2-[18F]fluoroethyl)-L-tyrosine based on a cartridge purification method

International Nuclear Information System (INIS)

Mueller, Dirk; Klette, Ingo; Kalb, Fabrizia; Baum, Richard P.

2011-01-01

Introduction: O-(2-[ 18 F]fluoroethyl)-L-tyrosine (FET) is widely used as a positron emission tomography tracer for brain tumors. Usually, a high-performance liquid chromatography (HPLC) purification at the end of the two-step synthesis is applied. In this work, we report an automatic radiosynthesis of FET with a purification procedure based on standard cartridges. Methods: O-(2-[ 18 F]fluoroethyl)-L-tyrosine was prepared by [ 18 F]fluoroethylation of L-tyrosine by a two-step synthesis using a modified [ 11 C]methionine module (Nuclear Interface). In the first reaction step, we synthesized [ 18 F]fluoroethyltosylate starting from [ 18 F]fluoride. After a purification step, L-tyrosine was [ 18 F]fluoroethylated with [ 18 F]fluoroethyltosylate. The final reaction mixture was purified by means of solid phase extraction. The FET was trapped on an SCX cartridge, eluted with saline solution and trapped again on an HRX cartridge. For a second purification step, the FET was eluted from the HRX cartridge with ammonium acetate buffer and collected on two SCX cartridges followed by a washing step with water. The final product was eluted with saline solution and neutralised with 450 μl NaHCO 3 solution (8.4%). Results: The synthesis was finished after 50 min and delivered the FET in a range of 3-16 GBq. The synthesis typically yielded 41% (21 experiments) of FET (d.c.) without an HPLC purification step. The radiochemical purity ranged between 97% and 100%. Conclusion: We present a radiosynthesis of FET where the usually used HPLC purification procedure has been substituted by a purification step based on standard cartridges. This method is useful for automatic modules without an expensive HPLC purification unit and for the routine production of FET.

Monitoring of anti-cancer treatment with (18)F-FDG and (18)F-FLT PET

DEFF Research Database (Denmark)

Jensen, Mette Munk; Kjaer, Andreas

2015-01-01

treatment effect early in a treatment course and by that to stratify patients into responders and non-responders. With 2-deoxy-2-[(18)F]fluoro-D-glucose ((18)F-FDG) and 3'-deoxy-3'-[(18)F]fluorothymidine((18)F-FLT) two of the cancer hallmarks, altered energy metabolism and increased cell proliferation, can......Functional imaging of solid tumors with positron emission tomography (PET) imaging is an evolving field with continuous development of new PET tracers and discovery of new applications for already implemented PET tracers. During treatment of cancer patients, a general challenge is to measure...... be visualized and quantified non-invasively by PET. With (18)F-FDG and (18)F-FLT PET changes in energy metabolism and cell proliferation can thereby be determined after initiation of cancer treatment in both clinical and pre-clinical studies in order to predict, at an early time-point, treatment response...

Treatment response evaluation with {sup 18}F-FDG PET/CT and {sup 18}F-NaF PET/CT in multiple myeloma patients undergoing high-dose chemotherapy and autologous stem cell transplantation

Energy Technology Data Exchange (ETDEWEB)

Sachpekidis, Christos [German Cancer Research Center (DKFZ), Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); University of Bern, Department of Nuclear Medicine, Inselspital, Bern University Hospital, Bern (Switzerland); Hillengass, J.; Wagner, B. [University Hospital Heidelberg, Department of Internal Medicine V, Heidelberg (Germany); Goldschmidt, H. [University Hospital Heidelberg, Department of Internal Medicine V, Heidelberg (Germany); National Center for Tumor Diseases (NCT) Heidelberg, Heidelberg (Germany); Haberkorn, U. [German Cancer Research Center (DKFZ), Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); University of Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); Kopka, K. [German Cancer Research Center (DKFZ), Department of Radiopharmaceutical Chemistry, Heidelberg (Germany); Dimitrakopoulou-Strauss, A. [German Cancer Research Center (DKFZ), Medical PET Group-Biological Imaging, Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany)

2017-01-15

The aim of this study was to assess the combined use of the radiotracers {sup 18}F-FDG and {sup 18}F-NaF in treatment response evaluation of a group of multiple myeloma (MM) patients undergoing high-dose chemotherapy (HDT) followed by autologous stem cell transplantation (ASCT) by means of static (whole-body) and dynamic PET/CT (dPET/CT). Thirty-four patients with primary, previously untreated MM scheduled for treatment with HDT followed by ASCT were enrolled in the study. All patients underwent PET/CT scanning with {sup 18}F-FDG and {sup 18}F-NaF before and after therapy. Treatment response by means of PET/CT was assessed according to the European Organization for Research and Treatment of Cancer (EORTC) 1999 criteria. The evaluation of dPET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modelling and a non-compartmental approach leading to the extraction of fractal dimension (FD). An analysis was possible in 29 patients: three with clinical complete response (CR) and 26 with non-CR (13 patients near complete response-nCR, four patients very good partial response-VGPR, nine patients partial response-PR). After treatment, {sup 18}F-FDG PET/CT was negative in 14/29 patients and positive in 15/29 patients, showing a sensitivity of 57.5 % and a specificity of 100 %. According to the EORTC 1999 criteria, {sup 18}F-FDG PET/CT-based treatment response revealed CR in 14 patients ({sup 18}F-FDG PET/CT CR), PR in 11 patients ({sup 18}F-FDG PET/CT PR) and progressive disease in four patients ({sup 18}F-FDG PET/CT PD). In terms of {sup 18}F-NaF PET/CT, 4/29 patients (13.8 %) had a negative baseline scan, thus failed to depict MM. Regarding the patients for which a direct lesion-to-lesion comparison was feasible, {sup 18}F-NaF PET/CT depicted 56 of the 129 {sup 18}F-FDG positive lesions (43 %). Follow-up {sup 18}F-NaF PET/CT showed persistence of 81.5 % of the baseline {sup 18}F-NaF

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)

Receiver operating characteristic (ROC) curve for classification of {sup 18}F-NaF uptake on PET/CT

Energy Technology Data Exchange (ETDEWEB)

Valadares, Agnes Araujo, E-mail: agnesvaladares@me.com [Universidade de Sao Paulo (HC/FM/USP), SP (Brazil). Hospital das Clinicas. Fac. de Mediciana; Duarte, Paulo Schiavom; Ono, Carla Rachel; Coura-Filho, George Barberio; Sado, Heitor Naoki; Carvalho, Giovanna [Instituto do Cancer do Estado de Sao Paulo Octavio Frias de Oliveira (ICESP), Sao Paulo, SP (Brazil). Servico de Medicina Nuclear; Sapienza, Marcelo Tatit; Buchpiguel, Carlos Alberto [Universidade de Sao Paulo (FM/USP), Sao Paulo, SP (Brazil). Fac. de Medicina. Dept. de Radiologia e Oncologia

2016-01-15

Objective: To assess the cutoff values established by ROC curves to classify {sup 18}F-NaF uptake as normal or malignant. Materials and Methods: PET/CT images were acquired 1 hour after administration of 185 MBq of {sup 18}F-NaF. Volumes of interest (VOIs) were drawn on three regions of the skeleton as follows: proximal right humerus diaphysis (HD), proximal right femoral diaphysis (FD) and first vertebral body (VB1), in a total of 254 patients, totalling 762 VOIs. The uptake in the VOIs was classified as normal or malignant on the basis of the radiopharmaceutical distribution pattern and of the CT images. A total of 675 volumes were classified as normal and 52 were classified as malignant. Thirty-five VOIs classified as indeterminate or nonmalignant lesions were excluded from analysis. The standardized uptake value (SUV) measured on the VOIs were plotted on an ROC curve for each one of the three regions. The area under the ROC (AUC) as well as the best cutoff SUVs to classify the VOIs were calculated. The best cutoff values were established as the ones with higher result of the sum of sensitivity and specificity. Results: The AUCs were 0.933, 0.889 and 0.975 for UD, FD and VB1, respectively. The best SUV cutoffs were 9.0 (sensitivity: 73%; specificity: 99%), 8.4 (sensitivity: 79%; specificity: 94%) and 21.0 (sensitivity: 93%; specificity: 95%) for UD, FD and VB1, respectively. Conclusion: The best cutoff value varies according to bone region of analysis and it is not possible to establish one value for the whole body. (author)

Membrane Potential-dependent Uptake of 18F-triphenylphosphonium - A New Voltage Sensor as an Imaging Agent for Detecting Burn-induced Apoptosis

Science.gov (United States)

Zhao, Gaofeng; Yu, Yong-Ming; Shoup, Timothy M.; Elmaleh, David R.; Bonab, Ali A.; Tompkins, Ronald G.; Fischman, Alan J.

2014-01-01

Background Mitochondrial dysfunction has been closely related to many pathological processes, such as cellular apoptosis. Alterations in organelle membrane potential are associated with mitochondrial dysfunction. A fluorine -18 labeled phosphonium compound: 18F-triphenylphosphonium (18F-TPP) was prepared to determine its potential use as a mitochondria-targeting radiopharmaceutical to evaluate cellular apoptosis. Methods Studies were conducted in both ex vivo cell lines and in vivo using a burned animal model. Uptake of 18F-TPP was assessed in PC-3 cells by gamma counting under the following conditions: graded levels of extra-cellular potassium concentrations, incubation with carbonyl cyanide m-chlorophenylhydrazone (CCCP) and staurosporine. Apoptosis was studied in a burn animal model using TUNEL staining and simultaneous assessment of 18F-TPP uptake by biodistribution. Results We found that stepwise membrane depolarization by potassium (K) resulted in a linear decrease in 18F-TPP uptake, with a slope of 0.62+/−0.08 and a correlation coefficient of 0.936+/−0.11. Gradually increased concentrations of CCCP lead to decreased uptakes of 18F-TPP. Staurosporine significantly decreased the uptake of 18F-TPP in PC-3 cells from 14.2+/−3.8% to 5.6+/−1.3% (P<0.001). Burn induced significant apoptosis (sham: 4.4 +/−1.8% vs. burn: 24.6+/− 6.7 %; p<0.005) and a reduced uptake of tracer in the spleens of burn injured animals as compared to sham burn controls (burn: 1.13+/−0.24% vs. sham: 3.28+/−0.67%; p<0.005). Biodistribution studies demonstrated that burn induced significant reduction in 18F-TPP uptake in spleen, heart, lung, and liver, which were associated with significantly increased apoptosis. Conclusions 18F-TPP is a promising new voltage sensor for detecting mitochondrial dysfunction and apoptosis in various tissues. PMID:24582214

Pet imaging of human pituitary 5-HT2 receptors with F-18 setoperone

Energy Technology Data Exchange (ETDEWEB)

Fischman, A.J.; Bonab, A.A.; Babich, J.W. [Massachusetts General Hospital, Boston, MA (United States)] [and others

1995-05-01

Serotonin (5-HT) receptors play an important role in the regulation of pituitary function. In particular, 5HT agonists stimulate ACTH, {beta}-endorphin, prolactin and growth hormone secretion but inhibit TSH release. 5-HT binding sites have been identified by autoradiographic studies of rat and human pituitary. In the present investigation, we used PET with F-18 setoperone to image 5-HT2 receptors in normal humans. Setoperone, a piperidine derivative with potent 5-HT2 receptor blocking properties was labelled with F-18 by nucleophilic substitution on the nitro derivative. After HPLC purification, specific activity was between 10,000 and 15,000 mCi/{mu} mole and radiochemical purity was >98%. Six healthy male volunteers were injected with 5-7 mCi of F-18. Setoperone and serial PET images and arterial blood samples were collected over 2 hrs. Specific binding to 5-HT2 receptors in the frontal cortex (FC), striatum (ST) and pituitary (P) was quantitated using the cerebellum (C) as reference. The tracer showed clear retention in FC, ST and P (known to contain a high density of 5-HT2 receptors) relative to C (known to be devoid of 5-HT2 receptors). In all subjects, FC/C, ST/C and P/C ratios increased during the first hr. and remained stable thereafter. For FC and ST, the ratios reached similar values; 3.92{plus_minus}0.73 and 3.53{plus_minus}0.32. For pituitary, a significantly higher ratio, was measured at all times; 6.53{plus_minus}1.82 (p<0.01). These results indicate that F-18 setoperone is an effective PET radiopharmaceutical for imaging 5-HT2 receptors in the human pituitary. Future applications of this agent could provide important new insights into neuroendocrine function.

Syntheses and in vitro evaluation of fluorinated naphthoxazines as dopamine D2/D3 receptor agonists: radiosynthesis, ex vivo biodistribution and autoradiography of [18F]F-PHNO

International Nuclear Information System (INIS)

Vasdev, Neil; Seeman, Philip; Garcia, Armando; Stableford, Winston T.; Nobrega, Jose N.; Houle, Sylvain; Wilson, Alan A.

2007-01-01

Introduction: Carbon-11-labeled (+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol ([ 11 C]-(+)-PHNO) is a dopamine D2/D3 agonist radioligand that is currently used to image the high-affinity state of dopamine receptors in humans with positron emission tomography (PET). The present study reports the preparation and evaluation of fluorinated (+)-PHNO derivatives. Methods: Five fluorinated (+)-PHNO derivatives were synthesized and tested in vitro for inhibition of binding of [ 3 H]domperidone in homogenates of rat striatum and inhibition of binding to [ 3 H]-(+)-PHNO in homogenates of human-cloned D2Long receptors in Chinese hamster ovary cells and rat striatum. Radiolabeling with fluorine-18 was carried out for the most promising candidate, N-fluoropropyl-(+)-HNO (F-PHNO), and ex vivo biodistribution and autoradiography studies with this radiopharmaceutical were performed in rodents. Results: (+)-PHNO and the fluorinated analogs inhibited binding of [ 3 H]domperidone and [ 3 H]-(+)-PHNO to the high- and low-affinity states of dopamine D2 receptors, consistent with D2 agonist behavior. The average dissociation constant at the high-affinity state of D2, K i High , was 0.4 nM for F-PHNO and proved to be equipotent with (+)-PHNO (0.7 nM). All other fluorinated derivatives were significantly less potent (K i High =2-102 nM). The most promising candidate, F-PHNO, was labeled with fluorine-18 in 5% uncorrected radiochemical yield, with respect to starting fluoride. Ex vivo biodistribution and autoradiography studies in rodents revealed that [ 18 F]F-PHNO rapidly enters the rodent brain. However, this radiotracer does not reveal specific binding in the brain and is rapidly cleared. Conclusions: Five novel dopamine D2/D3 agonists based on (+)-PHNO were synthesized and evaluated in vitro. F-PHNO was shown to behave as a potent D2 agonist in vitro and was therefore radiolabeled with fluorine-18. Despite the promising in vitro pharmacological profile, [ 18

Comparison of 18F-fluoro-L-DOPA, 18F-fluoro-deoxyglucose, and 18F-fluorodopamine PET and 123I-MIBG scintigraphy in the localization of pheochromocytoma and paraganglioma.

NARCIS (Netherlands)

Timmers, H.J.L.M.; Chen, C.C.; Carrasquillo, J.A.; Whatley, M.; Ling, A.; Havekes, B.; Eisenhofer, G.; Martiniova, L.; Adams, K.T.; Pacak, K.

2009-01-01

CONTEXT: Besides (123)I-metaiodobenzylguanidine (MIBG), positron emission tomography (PET) agents are available for the localization of paraganglioma (PGL), including (18)F-3,4-dihydroxyphenylalanine (DOPA), (18)F-fluoro-2-deoxy-D-glucose ((18)F-FDG), and (18)F-fluorodopamine ((18)F-FDA). OBJECTIVE:

18F-fluorodihydroxyphenylalanine PET/CT in pheochromocytoma and paraganglioma: relation to genotype and amino acid transport system L

International Nuclear Information System (INIS)

Feral, Chloe C.; Tissot, Floriane S.; Tosello, Lionel; Fakhry, Nicolas; Sebag, Frederic; Pacak, Karel; Taieb, David

2017-01-01

F-FDOPA is a highly sensitive and specific radiopharmaceutical for pheochromocytoma and paraganglioma (PPGL) imaging. However, 18 F-FDOPA might be falsely negative in these tumors, especially those related to mutations in succinate dehydrogenase genes (SDHx). The aim of the present study was to evaluate the relationship between expression of L-DOPA transporters and 18 F-FDOPA PET imaging results in PPGL. From 2007 to 2015, 175 patients with non-metastatic PPGL were evaluated by 18 F-FDOPA PET/CT for initial diagnosis/staging and follow-up. 18 F-FDOPA PET/CT was considered as falsely negative for at least one lesion in 10/126 (8%) patients (two sporadic, six SDHD, two SDHB PPGLs). The mRNA and protein expression levels of CD98hc and LATs were evaluated in samples with different genetic backgrounds and imaging phenotypes. The qRT-PCR and immunohistochemical analyses were performed in 14 and 16 tumor samples, respectively. The SDHx mutated samples exhibited a significant decrease in mRNA expression of LAT3 when compared to sporadic PPGLs (P = 0.042). There was also a statistical trend toward decreased CD98hc (P = 0.147) and LAT4 (P = 0.012) levels in SDHx vs sporadic PPGLs. No difference was observed for LAT1/LAT2 mRNA levels. LAT1 protein was expressed in 15 out of 16 (93.75%) SDHx tumors, regardless of the 18 F-FDOPA positivity. LAT1 and CD98hc were co-expressed in 6/8 18 F-FDOPA-negative PPGLs. In contrast, in one case with absence of LAT1/CD98hc, 18 F-FDOPA uptake was positive and attributed to LAT4 expression. We conclude that down-regulation of LAT1/CD98hc cannot explain the imaging phenotype of SDHx-related PPGLs. A reduced activity of LAT1 remains the primary hypothesis possibly due to a modification of intracellular amino acid content which may reduce 18 F-FDOPA uptake. (orig.)

[{sup 18}F]FE-SUPPY and [{sup 18}F]FE-SUPPY:2 - metabolic considerations

Energy Technology Data Exchange (ETDEWEB)

Haeusler, Daniela [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria); Nics, Lukas [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Nutritional Sciences, Univ. of Vienna, A-1090 Vienna (Austria); Mien, Leonhard-Key [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria); Ungersboeck, Johanna [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Inorganic Chemistry, Univ. of Vienna, A-1090 Vienna (Austria); Lanzenberger, Rupert R. [Dept. of Psychiatry and Psychotherapy, Medical Univ. of Vienna, A-1090 Vienna (Austria); Shanab, Karem [Dept. of Drug and Natural Product Synthesis, Univ. of Vienna, A-1090 Vienna (Austria); Sindelar, Karoline M. [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Viernstein, Helmut [Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria); Wagner, Karl-Heinz [Dept. of Nutritional Sciences, Univ. of Vienna, A-1090 Vienna (Austria); Dudczak, Robert; Kletter, Kurt [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Wadsak, Wolfgang [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Inorganic Chemistry, Univ. of Vienna, A-1090 Vienna (Austria); Mitterhauser, Markus [Dept. of Nuclear Medicine, Medical Univ. of Vienna, A-1090 Vienna (Austria); Dept. of Pharmaceutical Technology and Biopharmaceutics, Univ. of Vienna, A-1090 Vienna (Austria); Hospital Pharmacy of the General Hospital of Vienna, A-1090 Vienna (Austria)], E-mail: markus.mitterhauser@meduniwien.ac.at

2010-05-15

Introduction: Recently, [{sup 18}F]FE-SUPPY and [{sup 18}F]FE-SUPPY:2 were introduced as the first positron emission tomography (PET) tracers for the adenosine A{sub 3} receptor. Thus, aim of the present study was the metabolic characterization of the two adenosine A{sub 3} receptor PET tracers. Methods: In vitro carboxylesterase (CES) experiments were conducted using incubation mixtures containing different concentrations of the two substrates, porcine CES and phosphate-buffered saline. Enzymatic reactions were stopped by adding acetonitrile/methanol (10:1) after various time points and analyzed by a high-performance liquid chromatography (HPLC) standard protocol. In vivo experiments were conducted in male wild-type rats; tracers were injected through a tail vein. Rats were sacrificed after various time points (n=3), and blood and brain samples were collected. Sample cleanup was performed by an HPLC standard protocol. Results: The rate of enzymatic hydrolysis by CES demonstrated Michaelis-Menten constants in a micromolar range (FE-SUPPY, 20.15 {mu}M, and FE-SUPPY:2, 13.11 {mu}M) and limiting velocities of 0.035 and 0.015 {mu}M/min for FE-SUPPY and FE-SUPPY:2, respectively. Degree of metabolism in blood showed the following: 15 min pi 47.7% of [{sup 18}F]FE-SUPPY was intact compared to 33.1% of [{sup 18}F]FE-SUPPY:2; 30 min pi 30.3% intact [{sup 18}F]FE-SUPPY was found compared to 15.6% [{sup 18}F]FE-SUPPY:2. In brain, [{sup 18}F]FE-SUPPY:2 formed an early hydrophilic metabolite, whereas metabolism of [{sup 18}F]FE-SUPPY was not observed before 30 min pi Conclusion: Knowing that metabolism in rats is several times faster than in human, we conclude that [{sup 18}F]FE-SUPPY should be stable for the typical time span of a clinical investigation. As a consequence, from a metabolic point of view, one would tend to decide in favor of [{sup 18}F]FE-SUPPY.

Teaching and research in radiopharmaceuticals

Energy Technology Data Exchange (ETDEWEB)

Wiebe, L I [Noujaim Institute for Pharmaceutical Oncology Research, University of Alberta, Edmonton (Canada)

1998-08-01

Radiopharmaceuticals comprise a critical element of diagnostic and therapeutic clinical nuclear medicine. As well they contribute to more basic pre-clinical and clinical diagnostic studies such as the evaluation of new drugs and new drug formulations. Their development and utilization is based on the complex interaction of a number of disciplines including medicine, pharmacy, biochemistry, pharmacology, chemistry, physics and engineering. This technically-complex multidisciplinary base has impeded the development of a uniform curriculum of training for basic scientists and professionals who work with radiopharmaceuticals. the range of technical knowledge required is very broad; it ranges from chemical synthesis and radiolabelling, through a maze of biochemistry, pharmacology and now molecular biology, to GMP manufacture, dispensing and clinical consultation concerning use and interpretation of data. Clearly, no single discipline can (nor should) be expected to undertake in-depth training of radiopharmaceutical scientists, but equally clearly, there is need for the development of curricula that will develop specific components of the essential knowledge base. The `radiopharmaceutical` or `product` orientation of both teaching and research can be used to provide a focus for academic and professional organizations to develop `radiopharmacy` curricula that effectively train radiopharmaceutical practitioners for specific roles within the clinical, academic, government and industrial interests of radiopharmaceutical scientists. Currently, there is a plethora of segmented training programs, many of which are inadequately positioned to be of great value to the field or its practitioners. Efforts to re-focus radiopharmacy programs and to build professional recognition for them are bringing about harmonization of performance objectives, and leading to didactic and experiential curricula. The impact and evolution of regulatory processes will demand new and better

Teaching and research in radiopharmaceuticals

International Nuclear Information System (INIS)

Wiebe, L.I.

1998-01-01

Radiopharmaceuticals comprise a critical element of diagnostic and therapeutic clinical nuclear medicine. As well they contribute to more basic pre-clinical and clinical diagnostic studies such as the evaluation of new drugs and new drug formulations. Their development and utilization is based on the complex interaction of a number of disciplines including medicine, pharmacy, biochemistry, pharmacology, chemistry, physics and engineering. This technically-complex multidisciplinary base has impeded the development of a uniform curriculum of training for basic scientists and professionals who work with radiopharmaceuticals. the range of technical knowledge required is very broad; it ranges from chemical synthesis and radiolabelling, through a maze of biochemistry, pharmacology and now molecular biology, to GMP manufacture, dispensing and clinical consultation concerning use and interpretation of data. Clearly, no single discipline can (nor should) be expected to undertake in-depth training of radiopharmaceutical scientists, but equally clearly, there is need for the development of curricula that will develop specific components of the essential knowledge base. The 'radiopharmaceutical' or 'product' orientation of both teaching and research can be used to provide a focus for academic and professional organizations to develop 'radiopharmacy' curricula that effectively train radiopharmaceutical practitioners for specific roles within the clinical, academic, government and industrial interests of radiopharmaceutical scientists. Currently, there is a plethora of segmented training programs, many of which are inadequately positioned to be of great value to the field or its practitioners. Efforts to re-focus radiopharmacy programs and to build professional recognition for them are bringing about harmonization of performance objectives, and leading to didactic and experiential curricula. The impact and evolution of regulatory processes will demand new and better

Usefulness of [18F]-DA and [18F]-DOPA for PET imaging in a mouse model of pheochromocytoma

International Nuclear Information System (INIS)

Martiniova, Lucia; Cleary, Susannah; Lai, Edwin W.; Kiesewetter, Dale O.; Seidel, Jurgen; Dawson, Linda F.; Phillips, Jacqueline K.; Thomasson, David; Chen Xiaoyuan; Eisenhofer, Graeme; Powers, James F.; Kvetnansky, Richard

2012-01-01

Purpose: To evaluate the usefulness of [ 18 F]-6-fluorodopamine ([ 18 F]-DA) and [ 18 F]-L-6-fluoro-3,4-dihydroxyphenylalanine ([ 18 F]-DOPA) positron emission tomography (PET) in the detection of subcutaneous (s.c.) and metastatic pheochromocytoma in mice; to assess the expression of the norepinephrine transporter (NET) and vesicular monoamine transporters 1 and 2 (VMAT1 and VMAT2), all important for [ 18 F]-DA and [ 18 F]-DOPA uptake. Furthermore, to compare tumor detection by micro-computed tomography (microCT) to magnetic resonance imaging (MRI) in individual mouse. Methods: SUV max values were calculated from [ 18 F]-DA and [ 18 F]-DOPA PET, tumor-to-liver ratios (TLR) were obtained and expression of NET, VMAT1 and VMAT2 was evaluated. Results: [ 18 F]-DA detected less metastatic lesions compared to [ 18 F]-DOPA. TLR values for liver metastases were 2.26–2.71 for [ 18 F]-DOPA and 1.83–2.83 for [ 18 F]-DA. A limited uptake of [ 18 F]-DA was found in s.c. tumors (TLR=0.22-0.27) compared to [ 18 F]-DOPA (TLR=1.56-2.24). Overall, NET and VMAT2 were expressed in all organ and s.c. tumors. However, s.c. tumors lacked expression of VMAT1. We confirmed [ 18 F]-DA's high affinity for the NET for its uptake and VMAT1 and VMAT2 for its storage and retention in pheochromocytoma cell vesicles. In contrast, [ 18 F]-DOPA was found to utilize only VMAT2. Conclusion: MRI was superior in the detection of all organ tumors compared to microCT and PET. [ 18 F]-DOPA had overall better sensitivity than [ 18 F]-DA for the detection of metastases. Subcutaneous tumors were localized only with [ 18 F]-DOPA, a finding that may reflect differences in expression of VMAT1 and VMAT2, perhaps similar to some patients with pheochromocytoma where [ 18 F]-DOPA provides better visualization of lesions than [ 18 F]-DA.

A “dose on demand” Biomarker Generator for automated production of [18F]F− and [18F]FDG

International Nuclear Information System (INIS)

Awasthi, V.; Watson, J.; Gali, H.; Matlock, G.; McFarland, A.; Bailey, J.; Anzellotti, A.

2014-01-01

The University of Oklahoma—College of Pharmacy has installed the first Biomarker Generator (BG75) comprising a self-shielded 7.5-MeV proton beam positive ion cyclotron and an aseptic automated chemistry production and quality control module for production of [ 18 F]F − and clinical [ 18 F]FDG. Performance, reliability, and safety of the system for the production of “dose on demand” were tested over several months. No-carrier-added [ 18 F]F − was obtained through the 18 O(p,n) 18 F nuclear reaction by irradiation (20–40 min) of a >95% enriched [ 18 O]H 2 O target (280 μl) with a 7.5-MeV proton beam (3.5–5.0 μA). Automated quality control tests were performed on each dose. The HPLC-based analytical methods were validated against USP methods of quality control. [ 18 F]FDG produced by BG75 was tested in a mouse tumor model implanted with H441 human lung adenocarcinoma cells. After initial installment and optimization, the [ 18 F]F − production has been consistent since March 2011 with a maximum production of 400 to 450 mCi in a day. The average yield is 0.61 mCi/min and 0.92 mCi/min at 3.8 µA and 5 µA, respectively. The current target window has held up for over 25 weeks against >400 bombardment cycles. [ 18 F]FDG production has been consistent since June 2012 with an average of six doses/day in an automated synthesis mode (RCY≈50%). The release criteria included USP-specified limits for pH, residual solvents (acetonitrile/ethanol), kryptofix, radiochemical purity/identity, and filter integrity test. The entire automated operation generated minimal radiation exposure hazard to the operator and environment. As expected, [ 18 F]FDG produced by BG75 was found to delineate tumor volume in a mouse model of xenograft tumor. In summary, production and quality control of “[ 18 F]FDG dose on demand” have been accomplished in an automated and safe manner by the first Biomarker Generator. The implementation of a cGMP quality system is under way towards

Synthesis of 4-([{sup 18}F]fluoromethyl)-2-chlorophenylisothiocyanate: a novel bifunctional {sup 18}F-labelling agent

Energy Technology Data Exchange (ETDEWEB)

Wuest, F.; Mueller, M.; Bergmann, R. [Inst. fuer Bioanorganische und Radiopharmazeutische Chemie, FZ-Rossendorf e.V., Dresden (Germany)

2004-07-01

The one-step radiosynthesis of 4-([{sup 18}F]fluoromethyl)-2-chlorophenylisothiocyanate {sup 18}F-7 as a novel bifunctional {sup 18}F-labelling agent is described. Optimised reaction conditions in a remotely controlled synthesis module gave isothiocyanate {sup 18}F-7 in radiochemical yields of 45% (decay-corrected) within 40 min and high radiochemical purity of > 95% after solid-phase-extraction. Coupling of compound {sup 18}F-7 with the primary amine benzylamine as a model reaction afforded the corresponding ((4-[{sup 18}F]fluoromethyl)-2-chloro-phenyl)-benzyl thiourea {sup 18}F-8 in a high radiochemical yield of > 90%. Stability studies of thiourea {sup 18}F-8 in terms of radiodefluorination showed appreciable buffer stability at pH 7.4, whereas significant radiodefluorination was observed when {sup 18}F-8 was incubated in buffers at pH 3.6 and pH 9.4. Preliminary dynamic PET studies with thiourea {sup 18}F-8 in male Wistar rats showed high bone accumulation, indicative of high in vivo radiodefluorination. (orig.)

Forschungszentrum Rossendorf, Institute of Bioinorganic and Radiopharmaceutical Chemistry. Annual report 1995

International Nuclear Information System (INIS)

Johannsen, B.

1996-02-01

Research at the Institute of Bioinorganic and Radiopharmaceutical Chemistry of the Research Center Rossendorf is focused on radiotracers as molecular probes for diagnosis of disease. The research effort has two main components: -Positron emission tomography (PET) - technetium chemistry and radiopharmacology. The research activities of the Institute have been performed in three administratively classified groups. A PET tracer group is engaged in the chemistry and radiopharmacy of 11 C and 18 F compounds and in the setup of the PET center. A SPECT tracer group deals with the design, synthesis and chemical characterization of metal coordination compounds, primarily rhenium and technetium complexes. A biochemical group is working on SPECT and PET-relevant biochemical and biological projects. This includes the characterization and assessment of new compounds developed in the two synthetically oriented groups. The annual report presented here covers the research activities of the Institute of Bioinorganic and Radiopharmaceutical Chemistry in 1995. (orig.)

[{sup 18}F]FDG-PET in large vessel vasculitis; [{sup 18}F]FDG-PET bei Grossgefaess-Vaskulitiden

Energy Technology Data Exchange (ETDEWEB)

Hauser, A.S.D.; Walter, M.A. [Universitaetsspital Basel (Switzerland). Inst. fuer Nuklearmedizin

2007-06-15

[{sup 18}F]FDG-PET is a non-invasive metabolic imaging modality based on the regional distribution of fluorine-18-fluorodeoxyglucose that is highly effective in assessing the activity and the extent of giant cell arteritis and Takayasu's arteritis. It has shown to identify more affected vascular regions than morphologic imaging with Magnetic Resonance Imaging in both diseases. A visual grading of vascular [{sup 18}F]FDG-uptake helps to discriminate arteritis from atherosclerosis und therefore provides high specificity. High sensitivity is reached by scanning during the active inflammatory phase. [{sup 18}F]FDG-PET has the potential to develop into a valuable tool in the diagnostic work-up of giant cell arteritis and Takayasu's arteritis, respectively, and might become a first-line investigation technique. Therefore consensus regarding the most favorable imaging procedure as well as further clinical evidence is needed. The purpose of this review is to summarize current information on the present clinical data and to assist nuclear medicine practitioners in recommending, performing and interpreting the results of [{sup 18}F]FDG-PET in patients with suspected large vessel vasculitis. (orig.)

New horizons in cardiac innervation imaging. Introduction of novel 18F-labeled PET tracers

International Nuclear Information System (INIS)

Kobayashi, Ryohei; Chen, Xinyu; Werner, Rudolf A.; Lapa, Constantin; Javadi, Mehrbod S.; Higuchi, Takahiro

2017-01-01

Cardiac sympathetic nervous activity can be uniquely visualized by non-invasive radionuclide imaging techniques due to the fast growing and widespread application of nuclear cardiology in the last few years. The norepinephrine analogue 123 I-meta-iodobenzylguanidine ( 123 I-MIBG) is a single photon emission computed tomography (SPECT) tracer for the clinical implementation of sympathetic nervous imaging for both diagnosis and prognosis of heart failure. Meanwhile, positron emission tomography (PET) imaging has become increasingly attractive because of its higher spatial and temporal resolution compared to SPECT, which allows regional functional and dynamic kinetic analysis. Nevertheless, wider use of cardiac sympathetic nervous PET imaging is still limited mainly due to the demand of costly on-site cyclotrons, which are required for the production of conventional 11 C-labeled (radiological half-life, 20 min) PET tracers. Most recently, more promising 18 F-labeled (half-life, 110 min) PET radiopharmaceuticals targeting sympathetic nervous system have been introduced. These tracers optimize PET imaging and, by using delivery networks, cost less to produce. In this article, the latest advances of sympathetic nervous imaging using 18 F-labeled radiotracers along with their possible applications are reviewed. (orig.)

Assessment of glucose metabolism and cellular proliferation in multiple myeloma: a first report on combined 18F-FDG and 18F-FLT PET/CT imaging.

Science.gov (United States)

Sachpekidis, C; Goldschmidt, H; Kopka, K; Kopp-Schneider, A; Dimitrakopoulou-Strauss, A

2018-04-10

Despite the significant upgrading in recent years of the role of 18 F-FDG PET/CT in multiple myeloma (MM) diagnostics, there is a still unmet need for myeloma-specific radiotracers. 3'-Deoxy-3'-[ 18 F]fluorothymidine ( 18 F-FLT) is the most studied cellular proliferation PET agent, considered a potentially new myeloma functional imaging tracer. The aim of this pilot study was to evaluate 18 F-FLT PET/CT in imaging of MM patients, in the context of its combined use with 18 F-FDG PET/CT. Eight patients, four suffering from symptomatic MM and four suffering from smoldering MM (SMM), were enrolled in the study. All patients underwent 18 F-FDG PET/CT and 18 F-FLT PET/CT imaging by means of static (whole body) and dynamic PET/CT of the lower abdomen and pelvis (dPET/CT) in two consecutive days. The evaluation of PET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modeling. 18 F-FDG PET/CT demonstrated focal, 18 F-FDG avid, MM-indicative bone marrow lesions in five patients. In contrary, 18 F-FLT PET/CT showed focal, 18 F-FLT avid, myeloma-indicative lesions in only two patients. In total, 48 18 F-FDG avid, focal, MM-indicative lesions were detected with 18 F-FDG PET/CT, while 17 18 F-FLT avid, focal, MM-indicative lesions were detected with 18 F-FLT PET/CT. The number of myeloma-indicative lesions was significantly higher for 18 F-FDG PET/CT than for 18 F-FLT PET/CT. A common finding was a mismatch of focally increased 18 F-FDG uptake and reduced 18 F-FLT uptake (lower than the surrounding bone marrow). Moreover, 18 F-FLT PET/CT was characterized by high background activity in the bone marrow compartment, further complicating the evaluation of bone marrow lesions. Semi-quantitative evaluation revealed that both SUV mean and SUV max were significantly higher for 18 F-FLT than for 18 F-FDG in both MM lesions and reference tissue. SUV values were higher in MM lesions than in

Syntheses and in vitro evaluation of fluorinated naphthoxazines as dopamine D2/D3 receptor agonists: radiosynthesis, ex vivo biodistribution and autoradiography of [{sup 18}F]F-PHNO

Energy Technology Data Exchange (ETDEWEB)

Vasdev, Neil [PET Centre for Addiction and Mental Health, Toronto, Ontario, Canada, M5T-1R8 (Canada) and Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T-1R8 (Canada)]. E-mail: neil.vasdev@camhpet.ca; Seeman, Philip [Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T-1R8 (Canada); Department of Pharmacology, University of Toronto, Toronto, Ontario, M5S-1A8 (Canada); Garcia, Armando [PET Centre for Addiction and Mental Health, Toronto, Ontario, M5T-1R8 (Canada); Stableford, Winston T. [PET Centre for Addiction and Mental Health, Toronto, Ontario, M5T-1R8 (Canada); Nobrega, Jose N. [PET Centre for Addiction and Mental Health, Toronto, Ontario, M5T-1R8 (Canada); Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T-1R8 (Canada); Department of Pharmacology, University of Toronto, Toronto, Ontario, M5S-1A8 (Canada); Houle, Sylvain [PET Centre for Addiction and Mental Health, Toronto, Ontario, M5T-1R8 (Canada); Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T-1R8 (Canada); Wilson, Alan A. [PET Centre for Addiction and Mental Health, Toronto, Ontario, M5T-1R8 (Canada); Department of Psychiatry, University of Toronto, Toronto, Ontario, M5T-1R8 (Canada)

2007-02-15

Introduction: Carbon-11-labeled (+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol ([{sup 11}C]-(+)-PHNO) is a dopamine D2/D3 agonist radioligand that is currently used to image the high-affinity state of dopamine receptors in humans with positron emission tomography (PET). The present study reports the preparation and evaluation of fluorinated (+)-PHNO derivatives. Methods: Five fluorinated (+)-PHNO derivatives were synthesized and tested in vitro for inhibition of binding of [{sup 3}H]domperidone in homogenates of rat striatum and inhibition of binding to [{sup 3}H]-(+)-PHNO in homogenates of human-cloned D2Long receptors in Chinese hamster ovary cells and rat striatum. Radiolabeling with fluorine-18 was carried out for the most promising candidate, N-fluoropropyl-(+)-HNO (F-PHNO), and ex vivo biodistribution and autoradiography studies with this radiopharmaceutical were performed in rodents. Results: (+)-PHNO and the fluorinated analogs inhibited binding of [{sup 3}H]domperidone and [{sup 3}H]-(+)-PHNO to the high- and low-affinity states of dopamine D2 receptors, consistent with D2 agonist behavior. The average dissociation constant at the high-affinity state of D2, K {sub i} {sup High}, was 0.4 nM for F-PHNO and proved to be equipotent with (+)-PHNO (0.7 nM). All other fluorinated derivatives were significantly less potent (K {sub i} {sup High}=2-102 nM). The most promising candidate, F-PHNO, was labeled with fluorine-18 in 5% uncorrected radiochemical yield, with respect to starting fluoride. Ex vivo biodistribution and autoradiography studies in rodents revealed that [{sup 18}F]F-PHNO rapidly enters the rodent brain. However, this radiotracer does not reveal specific binding in the brain and is rapidly cleared. Conclusions: Five novel dopamine D2/D3 agonists based on (+)-PHNO were synthesized and evaluated in vitro. F-PHNO was shown to behave as a potent D2 agonist in vitro and was therefore radiolabeled with fluorine-18. Despite the

Characterization of biological features of a rat F98 GBM model: A PET-MRI study with [18F]FAZA and [18F]FDG

International Nuclear Information System (INIS)

Belloli, Sara; Brioschi, Andrea; Politi, Letterio Salvatore; Ronchetti, Francesca; Calderoni, Sara; Raccagni, Isabella; Pagani, Antonella; Monterisi, Cristina; Zenga, Francesco; Zara, Gianpaolo; Fazio, Ferruccio; Mauro, Alessandro

2013-01-01

Introduction: The prognosis of malignant gliomas remains largely unsatisfactory for the intrinsic characteristics of the pathology and for the delayed diagnosis. Multimodal imaging based on PET and MRI may assess the dynamics of disease onset and progression allowing the validation of preclinical models of glioblastoma multiforme (GBM). The aim of this study was the characterization of a syngeneic rat model of GBM using combined in vivo imaging and immunohistochemistry. Methods: Four groups of Fischer rats were implanted in a subcortical region with increasing concentration of rat glioma F98 cells and weekly monitored with Gd-MR, [ 18 F]FDG- and [ 18 F]FAZA-PET starting one week after surgery. Different targets were evaluated on post mortem brain specimens using immunohistochemistry: VEGF, GFAP, HIF-1α, Ki-67 and nestin. Results: Imaging results indicated that tumor onset but not progression was related to the number of F98 cells. Hypoxic regions identified with [ 18 F]FAZA and high-glucose metabolism regions recognized with [ 18 F]FDG were located respectively in the core and in external areas of the tumor, with partial overlap and remodeling during disease progression. Histological and immunohistochemical analysis confirmed PET/MRI results and revealed that our model resumes biological characteristics of human GBM. IHC and PET studies showed that necrotic regions, defined on the basis of [ 18 F]FDG uptake reduction, may include hypoxic clusters of vital tumor tissue identified with [ 18 F]FAZA. This last information is particularly relevant for the identification of the target volume during image-guided radiotherapy. Conclusions: In conclusion, the combined use of PET and MRI allows in vivo monitoring of the biological modification of F98 lesions during tumor progression

Preclinical test: bacterial reverse mutation test for 18F-fluorocholine produced in CDTN

International Nuclear Information System (INIS)

Mendes, Bruno M.; Bispo, Ana Carolina A.; Campos, Danielle C.; Silva, Juliana B.

2013-01-01

The choline labeled with fluorine-18 (18FCH) is being considered as a great importance radiopharmaceutical due to its effective detection of many type of malignant neoplasm. The research related to 18 F-fluorocholine synthesis in CDTN was initiated in 2010. In order to obtain clinical research approval, as well as to register 18 FCH for marketing, safety and efficacy preclinical testing are required. The present work evaluated the 18 FCH genotoxic potential through the bacterial reverse mutation test (Ames test) using Salmonella typhimurium TA-98, TA-100, TA-1535 and TA-1537 strains and Escherichia coli WP2 uvrA strain. The reverse mutation test in bacteria for fluorcolina was conducted in two stages. Initially the method was applied to 'cold' fluorocholine molecule (19FCH). Subsequently, the decayed product of 18 FCH synthesis was evaluated. The first step was performed in order to examine the FCH molecule mutagenicity. The second was carried out to determine the mutagenic potential of final product. All strains were tested in triplicate for each exposure concentration, in the presence and absence of metabolic activation (S-9 mix - 10%). There were no statistically significant increases in revertant colonies rate for any strains tested after their exposure to decayed 18 FCH or 19 FCH. The number of revertant colonies in positive controls was significantly higher than that observed in significant increases in revertant colonies rate for any strains tested after their exposure to decayed 18 FCH or 19 FCH. The number of revertant colonies in positive controls was significantly higher than that observed in negative controls. Based on results of this assay, 18 FCH and 19 FCH, at tested doses, were found to be non-mutagenic in bacterial reverse mutation test. (author)

Hospitable radiopharmaceuticals

International Nuclear Information System (INIS)

Gonzalez, M.B.

1994-01-01

Two types of hospitalary radiopharmaceutical was given in Nuclear Medicine: the centralized and hospitalary radiopharmaceuticals. The good practice in the use, instrumentation and quality control of radiopharmaceuticals are used in nuclear medicine for diagnostic and therapy diseases

F-18-fluorodeoxyglucose-positron emission tomography in colorectal cancer

International Nuclear Information System (INIS)

Joerg, L.; Langsteger, W.

2002-01-01

Whole-body positron emission tomography (PET) with the radiolabeled glucose analog F-18-fluorodeoxyglucose (F-18-FDG) is a sensitive diagnostic tool that images tumors based on increased uptake of glucose. Several recent publications have shown that F-18-fluorodeoxyglucose-positron emission tomography is more sensitive than computed-tomography (CT) in detecting colorectal cancer. In patients with increasing CEA (carcinoembryonic antigen) and no evidence of recurrent disease on CT F-18-fluorodeoxyglucose-positron emission tomography often detects recurrent cancer. In all, patient management seems to be changed in about 25 % of patients who undergo F-18-fluorodeoxyglucose-positron emission tomography in addition to standard staging procedure. Limited reports to date on both chemotherapy and radiotherapy support the role of F-18-fluorodeoxyglucose-positron emission tomography in assessing treatment response. Also regarding preoperative staging of primary colorectal cancer the literature is very limited. (author)

Doubling-resolution analog-to-digital conversion based on PIC18F45K80

Directory of Open Access Journals (Sweden)

Yueyang Yuan

2014-08-01

Full Text Available Aiming at the analog signal being converted into the digital with a higher precision, a method to improve the analog-to-digital converter (ADC resolution is proposed and described. Based on the microcomputer PIC18F45K80 in which the internal ADC modules are embedded, a circuit is designed for doubling the resolution of ADC. According to the circuit diagram, the mathematical formula for calculating this resolution is derived. The corresponding software and print circuit board assembly is also prepared. With the experiment, a 13 bit ADC is achieved based on the 12 bit ADC module predesigned in the PIC18F45K80.

Carrier-added and no-carrier-added syntheses of (/sup 18/F)spiroperidol and (/sub 18/F)haloperidol

Energy Technology Data Exchange (ETDEWEB)

Kilbourn, M R; Welch, M J; Dence, C S; Tewson, T J; Saji, H; Maeda, M

1984-07-01

Syntheses of (18F)haloperidol and (18F)spiroperidol in both no-carrier-added and carrier-added forms have been accomplished. The no-carrier-added (18F)butyrophenone neuroleptics were prepared in low (less than 2%) yield by acid decomposition of aryl piperidine triazenes. Carrier-added 18F-neuroleptics were prepared in better (5-17%) yields by 18F-for-19F nucleophilic aromatic substitution. The preparation of all synthetic precursors, and procedures for radiolabeling are fully described.

18F-DOPA PET/CT for assessment of response to induction chemotherapy in a child with high-risk neuroblastoma

International Nuclear Information System (INIS)

Piccardo, Arnoldo; Lopci, Egesta; Foppiani, Luca; Morana, Giovanni; Conte, Massimo

2014-01-01

Functional imaging plays a crucial role in the assessment of neuroblastoma. The evaluation of response to induction chemotherapy is a cornerstone in scheduling proper treatment management in patients affected by high-risk neuroblastoma. 123 I-metaiodobenzylguanidine has been recognized as the radiopharmaceutical of choice in neuroblastoma assessment. To date, the clinical role of PET/CT in pediatric malignancy is not well established. 18 F-DOPA-PET/CT has been recently used in neuroblastoma, and compared with 123 I-MIBG-scan. Scant new data are available about the role of this tool in the evaluation of treatment response after induction chemotherapy. We investigate the role of 18 F-DOPA-PET/CT in characterizing the response to induction chemotherapy in a child affected by high-risk-neuroblastoma, in whom the rare association of 123 I-MIBG-negative primary tumor and MIBG-positive bone marrow metastases was observed. (orig.)

(18)F-alfatide II and (18)F-FDG dual-tracer dynamic PET for parametric, early prediction of tumor response to therapy.

Science.gov (United States)

Guo, Jinxia; Guo, Ning; Lang, Lixin; Kiesewetter, Dale O; Xie, Qingguo; Li, Quanzheng; Eden, Henry S; Niu, Gang; Chen, Xiaoyuan

2014-01-01

A single dynamic PET acquisition using multiple tracers administered closely in time could provide valuable complementary information about a tumor's status under quasiconstant conditions. This study aimed to investigate the utility of dual-tracer dynamic PET imaging with (18)F-alfatide II ((18)F-AlF-NOTA-E[PEG4-c(RGDfk)]2) and (18)F-FDG for parametric monitoring of tumor responses to therapy. We administered doxorubicin to one group of athymic nude mice with U87MG tumors and paclitaxel protein-bound particles to another group of mice with MDA-MB-435 tumors. To monitor therapeutic responses, we performed dual-tracer dynamic imaging, in sessions that lasted 90 min, starting with injection via the tail vein catheters with (18)F-alfatide II, followed 40 min later by (18)F-FDG. To achieve signal separation of the 2 tracers, we fit a 3-compartment reversible model to the time-activity curve of (18)F-alfatide II for the 40 min before (18)F-FDG injection and then extrapolated to 90 min. The (18)F-FDG tumor time-activity curve was isolated from the 90-min dual-tracer tumor time-activity curve by subtracting the fitted (18)F-alfatide II tumor time-activity curve. With separated tumor time-activity curves, the (18)F-alfatide II binding potential (Bp = k3/k4) and volume of distribution (VD) and (18)F-FDG influx rate ((K1 × k3)/(k2 + k3)) based on the Patlak method were calculated to validate the signal recovery in a comparison with 60-min single-tracer imaging and to monitor therapeutic response. The transport and binding rate parameters K1-k3 of (18)F-alfatide II, calculated from the first 40 min of the dual-tracer dynamic scan, as well as Bp and VD correlated well with the parameters from the 60-min single-tracer scan (R(2) > 0.95). Compared with the results of single-tracer PET imaging, (18)F-FDG tumor uptake and influx were recovered well from dual-tracer imaging. On doxorubicin treatment, whereas no significant changes in static tracer uptake values of (18)F-alfatide II

Automated radiosynthesis of no-carrier-added 4-[18F]fluoroiodobenzene: a versatile building block in 18F radiochemistry.

Science.gov (United States)

Way, Jenilee Dawn; Wuest, Frank

2014-02-01

4-[18F]Fluoroiodobenzene ([18F]FIB) is a versatile building block in 18F radiochemistry used in various transition metal-mediated C-C and C-N cross-coupling reactions and [18F]fluoroarylation reactions. Various synthesis routes have been described for the preparation of [18F]FIB. However, to date, no automated synthesis of [18F]FIB has been reported to allow access to larger amounts of [18F]FIB in high radiochemical and chemical purity. Herein, we describe an automated synthesis of no-carrier-added [18F]FIB on a GE TRACERlab™ FX automated synthesis unit starting from commercially available(4-iodophenyl)diphenylsulfonium triflate as the labelling precursor. [18F]FIB was prepared in high radiochemical yields of 89 ± 10% (decay-corrected, n = 7) within 60 min, including HPLC purification. The radiochemical purity exceeded 95%, and specific activity was greater than 40 GBq/μmol. Typically, from an experiment, 6.4 GBq of [18F]FIB could be obtained starting from 10.4 GBq of [18F]fluoride.

Carrier-added and no-carrier-added syntheses of (/sup 18/F)spiroperidol and (/sup 18/F)haloperidol

Energy Technology Data Exchange (ETDEWEB)

Kilbourn, M R; Welch, M J; Dence, C S; Tewson, T J; Saji, H; Maeda, M [Washington Univ., St. Louis, MO (USA). Edward Mallinckrodt Inst. of Radiology

1984-07-01

Syntheses of (/sup 18/F)haloperidol and (/sup 18/F)spiroperidol in both no-carrier-added and carrier-added forms have been accomplished. The no-carrier-added (/sup 18/F)butyrophenone neuroleptics were prepared in low (<2%) yield by acid decomposition of aryl piperidine triazenes. Carrier-added /sup 18/F-neuroleptics were prepared in better (5-17%) yields by /sup 18/F-for-/sup 19/F nucleophilic aromatic substitution. The preparation of all synthetic precursors, and procedures for radiolabeling are fully described.

{sup 18}F-fluorodihydroxyphenylalanine PET/CT in pheochromocytoma and paraganglioma: relation to genotype and amino acid transport system L

Energy Technology Data Exchange (ETDEWEB)

Feral, Chloe C.; Tissot, Floriane S.; Tosello, Lionel [INSERM U1081, Institute for Research on Cancer and Aging of Nice (IRCAN), Nice (France); Fakhry, Nicolas [Aix-Marseille University, Department of Otorhinolaryngology-Head and Neck Surgery, Conception Hospital, Marseille (France); Sebag, Frederic [Aix-Marseille University, Department of Endocrine Surgery, Conception Hospital, Marseille (France); Pacak, Karel [Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD (United States); Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Marseille (France)

2017-05-15

F-FDOPA is a highly sensitive and specific radiopharmaceutical for pheochromocytoma and paraganglioma (PPGL) imaging. However, {sup 18}F-FDOPA might be falsely negative in these tumors, especially those related to mutations in succinate dehydrogenase genes (SDHx). The aim of the present study was to evaluate the relationship between expression of L-DOPA transporters and {sup 18}F-FDOPA PET imaging results in PPGL. From 2007 to 2015, 175 patients with non-metastatic PPGL were evaluated by {sup 18}F-FDOPA PET/CT for initial diagnosis/staging and follow-up. {sup 18}F-FDOPA PET/CT was considered as falsely negative for at least one lesion in 10/126 (8%) patients (two sporadic, six SDHD, two SDHB PPGLs). The mRNA and protein expression levels of CD98hc and LATs were evaluated in samples with different genetic backgrounds and imaging phenotypes. The qRT-PCR and immunohistochemical analyses were performed in 14 and 16 tumor samples, respectively. The SDHx mutated samples exhibited a significant decrease in mRNA expression of LAT3 when compared to sporadic PPGLs (P = 0.042). There was also a statistical trend toward decreased CD98hc (P = 0.147) and LAT4 (P = 0.012) levels in SDHx vs sporadic PPGLs. No difference was observed for LAT1/LAT2 mRNA levels. LAT1 protein was expressed in 15 out of 16 (93.75%) SDHx tumors, regardless of the {sup 18}F-FDOPA positivity. LAT1 and CD98hc were co-expressed in 6/8 {sup 18}F-FDOPA-negative PPGLs. In contrast, in one case with absence of LAT1/CD98hc, {sup 18}F-FDOPA uptake was positive and attributed to LAT4 expression. We conclude that down-regulation of LAT1/CD98hc cannot explain the imaging phenotype of SDHx-related PPGLs. A reduced activity of LAT1 remains the primary hypothesis possibly due to a modification of intracellular amino acid content which may reduce {sup 18}F-FDOPA uptake. (orig.)

In vivo biodistribution of two [18F]-labelled muscarinic cholinergic receptor ligands: 2-[18F]- and 4-[18F]-fluorodexetimide

International Nuclear Information System (INIS)

Wilson, A.A.; Scheffel, U.A.; Dannals, R.F.; Stathis, M.; Ravert, H.T.; Wagner, H.N. Jr.

1991-01-01

Two [ 18 F]-labelled analogues of the potent muscarinic cholinergic receptor (m-AChR) antagonist, dexetimide, were evaluated as potential ligands for imaging m-AChR by positron emission tomography (PET). Intravenous administration of both 2-[ 18 F]- or 4-[ 18 F]-fluorodexetimide resulted in high brain uptake of radioactivity in mice. High binding levels were observed in m-AChR rich areas, such as cortex and striatum, with low levels in the receptor-poor cerebellum. Uptake of radioactivity was saturable and could be blocked by pre-administration of dexetimide or atropine. Drugs with different sites of action were ineffective at blocking receptor binding. The results indicate that both radiotracers are promising candidates for use in PET studies

Complementary roles of tumour specific PET tracer {sup 18}F-FAMT to {sup 18}F-FDG PET/CT for the assessment of bone metastasis

Energy Technology Data Exchange (ETDEWEB)

Morita, Motoho [Gunma University Hospital, Department of General Medicine, Maebashi, Gunma (Japan); Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Higuchi, Tetsuya; Tokue, Azusa; Arisaka, Yukiko; Tsushima, Yoshito [Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Achmad, Arifudin [Gunma University Graduate School of Medicine, Department of Diagnostic Radiology and Nuclear Medicine, Maebashi, Gunma (Japan); Gadjah Mada University, Department of Radiology, Faculty of Medicine, Yogyakarta (Indonesia)

2013-10-15

The usefulness of {sup 18}F-FDG PET/CT for bone metastasis evaluation has already been established. The amino acid PET tracer [{sup 18}F]-3-fluoro-alpha-methyl tyrosine ({sup 18}F-FAMT) has been reported to be highly specific for malignancy. We evaluated the additional value of {sup 18}F-FAMT PET/CT to complement {sup 18}F-FDG PET/CT in the evaluation of bone metastasis. This retrospective study included 21 patients with bone metastases of various cancers who had undergone both {sup 18}F-FDG and {sup 18}F-FAMT PET/CT within 1 month of each other. {sup 18}F-FDG-avid bone lesions suspicious for malignancy were carefully selected based on the cut-off value for malignancy, and the SUVmax of the {sup 18}F-FAMT in the corresponding lesions were evaluated. A total of 72 {sup 18}F-FDG-positive bone lesions suspected to be metastases in the 21 patients were used as the reference standard. {sup 18}F-FAMT uptake was found in 87.5 % of the lesions. In the lesions of lung cancer origin, the uptake of the two tracers showed a good correlation (40 lesions, r = 0.68, P < 0.01). Bone metastatic lesions of oesophageal cancer showed the highest average of {sup 18}F-FAMT uptake. Bone metastatic lesions of squamous cell carcinoma showed higher {sup 18}F-FAMT uptake than those of adenocarcinoma. No significant difference in {sup 18}F-FAMT uptake was seen between osteoblastic and osteolytic bone metastatic lesions. The usefulness of {sup 18}F-FAMT PET/CT for bone metastasis detection regardless of the lesion phenotype was demonstrated. The fact that {sup 18}F-FAMT uptake was confirmed by {sup 18}F-FDG uptake suggests that {sup 18}F-FAMT PET/CT has the potential to complement {sup 18}F-FDG PET/CT for the detection of bone metastases. (orig.)

Carbidopa and physiological distribution of the 6-L-[{sup 18}F]-fluoro-dihydroxy-phenylalanine ({sup 18}F-DOPA); Carbidopa et biodistribution physiologique de la 6-L-[{sup 18}F]-fluorodihydroxyphenylalanine ({sup 18}F-DOPA)

Energy Technology Data Exchange (ETDEWEB)

Detour, J.; Hammer, C.; Lucas, A. [Hopitaux universitaires de Strasbourg, Service de radiopharmacie, 67 (France); Imperiale, A.; Constantinesco, A. [Hopitaux universitaires de Strasbourg, Service de biophysique et medecine nucleaire, 67 (France); Beretz, L. [Hopitaux universitaires de Strasbourg, pole de pharmacie-pharmacologie, 67 (France)

2010-07-01

Purpose: The administration of carbidopa, an peripheral inhibitor of decarboxylase DOPA, may be performed prior to a full body PET scan {sup 18}F-DOPA. There is currently no consensus regarding the routine use of this metabolic preparation (200 mg, 100 mg, 2 mg / kg, no pre-medication). Conclusions: The absence of pre-medication clearly increases pancreatic uptake of {sup 18}F-D.O.P.A.. These results suggest to reconsider the metabolic preparation based on carbidopa, particularly in cases of suspected clinico biological forms of diffuse hyper-insulinism (nesidioblastosis). Pre-medication in cases of digestive neuroendocrine tumors should be reconsidered. The dose-dependent effect of pre-medication on the tumor uptake remains to be explored. (N.C.)

Longitudinal imaging of Alzheimer pathology using [11C]PIB, [18F]FDDNP and [18F]FDG PET

International Nuclear Information System (INIS)

Ossenkoppele, Rik; Tolboom, Nelleke; Adriaanse, Sofie F.; Foster-Dingley, Jessica C.; Boellaard, Ronald; Yaqub, Maqsood; Windhorst, Albert D.; Lammertsma, Adriaan A.; Berckel, Bart N.M. van; Barkhof, Frederik; Scheltens, Philip; Flier, Wiesje M. van der

2012-01-01

[ 11 C]PIB and [ 18 F]FDDNP are PET tracers for in vivo detection of the neuropathology underlying Alzheimer's disease (AD). [ 18 F]FDG is a glucose analogue and its uptake reflects metabolic activity. The purpose of this study was to examine longitudinal changes in these tracers in patients with AD or mild cognitive impairment (MCI) and in healthy controls. Longitudinal, paired, dynamic [ 11 C]PIB and [ 18 F]FDDNP (90 min each) and static [ 18 F]FDG (15 min) PET scans were obtained in 11 controls, 12 MCI patients and 8 AD patients. The mean interval between baseline and follow-up was 2.5 years (range 2.0-4.0 years). Parametric [ 11 C]PIB and [ 18 F]FDDNP images of binding potential (BP ND ) and [ 18 F]FDG standardized uptake value ratio (SUVr) images were generated. A significant increase in global cortical [ 11 C]PIB BP ND was found in MCI patients, but no changes were observed in AD patients or controls. Subsequent regional analysis revealed that this increase in [ 11 C]PIB BP ND in MCI patients was most prominent in the lateral temporal lobe (p 18 F]FDDNP, no changes in global BP ND were found. [ 18 F]FDG uptake was reduced at follow-up in the AD group only, especially in frontal, parietal and lateral temporal lobes (all p 11 C]PIB binding (ρ = -0.42, p 18 F]FDG uptake (ρ = 0.54, p 18 F]FDDNP binding (ρ = -0.18, p = 0.35) were not. [ 11 C]PIB and [ 18 F]FDG track molecular changes in different stages of AD. We found increased amyloid load in MCI patients and progressive metabolic impairment in AD patients. [ 18 F]FDDNP seems to be less useful for examining disease progression. (orig.)

4- 18F]fluoroarylalkylethers via an improved synthesis of n.c.a. 4- 18F]fluorophenol

International Nuclear Information System (INIS)

Ludwig, Thomas; Ermert, Johannes; Coenen, Heinz H.

2002-01-01

This paper describes the improved synthesis of n.c.a. 4- 18 F]fluorophenol for the preparation of 18 F-labeled alkylarylethers. Nucleophilic fluorination of substituted benzophenone derivatives yielded n.c.a. 4- 18 F]fluoro-4'-substituted benzophenones with 80- 90 % RCY, which were converted to benzoic acid phenylesters by treatment with peracetic acid. Strong electron-withdrawing substituents like nitro, cyano and trifluoromethyl favor a fluorophenyl-to-oxygen migration resulting in the formation of corresponding benzoic acid fluorophenylesters. N.c.a. 18 F]fluorophenol is almost quantitatively formed after hydrolysis and can easily be converted with alkylhalides into n.c.a. 18 F]fluoroarylalkylethers

Synthesis of n.c.a. {sup 18}F-fluorinated NMDA- and D{sub 4}-receptor ligands via [{sup 18}F]fluorobenzenes; Traegerarme Synthese {sup 18}F-markierter, ausgewaehlter NMDA- und D{sub 4}-Rezeptorliganden durch Einsatz geeigneter [{sup 18}F]Fluorbenzolderivate

Energy Technology Data Exchange (ETDEWEB)

Ludwig, T

2005-11-01

In this thesis new strategies were developed and evaluated for the no-carrier-added (n.c.a.) {sup 18}F-labelling of receptor ligands as radiodiagnostics for characterization of brain receptors using positron-emission-tomography (PET). Special emphasis was placed on the synthesis of n.c.a. ({+-})-3-(4-hydroxy-4-(4-[{sup 18}F]fluorophenyl)-piperidin-l-yl)chroman-4,7-diol, a ligand with high affinity for the NR2B subtype of NMDA receptors and n.c.a. (3-(4-[{sup 18}F]fluorphenoxy)propyl)-(2-(4-tolylphenoxy)ethyl)amine ([{sup 18}F]FPTEA) a dopamine D{sub 4} receptor ligand. In order to synthesize n.c.a. ({+-})-3-(4-hydroxy-4-(4-[{sup 18}F]fluorophenyl)-piperidin-l-yl)chroman-4,7-diol the {sup 18}F-fluoroarylation method via metallorganic intermediates was modified and improved. The suitability of the organometallic {sup 18}F-fluoroarylation agents was proven with several model compounds. High radiochemical yields of 20-30% were obtained also with piperidinone-derivatives. The preparation of a suitable precursor for the synthesis of the NMDA receptor ligand, however, could not be achieved by synthesis of appropriate 1,3-dioxolane protected piperidinone derivatives. Further, the synthesis of n.c.a. ([{sup 18}F]fluoroaryloxy)alkylamines via n.c.a. 4-[{sup 18}F]fluorophenol was developed and evaluated. The synthesis of n.c.a. [{sup 18}F]fluoroarylethers with corresponding model compounds was optimized and led to a radiochemical yield of 25-60%, depending on the alkylhalide used. The preparation of n.c.a. 1-(3-bromopropoxy)-4-[{sup 18}F]fluorobenzene proved advantageous in comparison to direct use of 4-[{sup 18}]fluorophenol for coupling with a corresponding N-protected precursor for the synthesis of n.c.a. [{sup 18}F]FPTEA. With regard to the radiochemical yields and the loss of activity during the synthesis and isolation of n.c.a. 4-[{sup 18}F]fluorophenol and n.c.a. 1-(3-bromopropoxy)-4-[{sup 18}F]fluorobenzene, [{sup 18}F]FPTEA was obtained by reaction with 2-(4-tolyloxy

Fluorine-18 NaF PET imaging of child abuse

Energy Technology Data Exchange (ETDEWEB)

Drubach, Laura A. [Children' s Hospital Boston and Harvard Medical School, Department of Radiology, Division of Nuclear Medicine/PET, Boston, MA (United States); Sapp, Mark.V. [School of Osteopathic Medicine, Child Abuse Research Education and Services (CARES) Institute University of Medicine and Dentistry of New Jersey, New Jersey (United States); Laffin, Stephen [Children' s Hospital Boston, Department of Radiology, Division of Nuclear Medicine/PET, Boston, MA (United States); Kleinman, Paul K. [Children' s Hospital Boston and Harvard Medical School, Department of Radiology, Division of Musculoskeletal Imaging, Boston, MA (United States)

2008-07-15

We describe the use of {sup 18}F-NaF positron emission tomography (PET) whole-body imaging for the evaluation of skeletal trauma in a case of suspected child abuse. To our knowledge, 18F NaF PET has not been used in the past for the evaluation of child abuse. In our patient, this technique detected all sites of trauma shown by initial and follow-up skeletal surveys, including bilateral metaphyseal fractures of the proximal humeri. Fluorine-18 NaF PET has potential advantage over Tc-99m-labeled methylene diphosphonate (MDP) based upon superior image contrast and spatial resolution. (orig.)

Fluorine-18 NaF PET imaging of child abuse

International Nuclear Information System (INIS)

Drubach, Laura A.; Sapp, Mark V.; Laffin, Stephen; Kleinman, Paul K.

2008-01-01

We describe the use of 18 F-NaF positron emission tomography (PET) whole-body imaging for the evaluation of skeletal trauma in a case of suspected child abuse. To our knowledge, 18F NaF PET has not been used in the past for the evaluation of child abuse. In our patient, this technique detected all sites of trauma shown by initial and follow-up skeletal surveys, including bilateral metaphyseal fractures of the proximal humeri. Fluorine-18 NaF PET has potential advantage over Tc-99m-labeled methylene diphosphonate (MDP) based upon superior image contrast and spatial resolution. (orig.)

Procedures for the GMP-Compliant Production and Quality Control of [18F]PSMA-1007: A Next Generation Radiofluorinated Tracer for the Detection of Prostate Cancer

Directory of Open Access Journals (Sweden)

Jens Cardinale

2017-09-01

Full Text Available Radiolabeled tracers targeting the prostate-specific membrane antigen (PSMA have become important radiopharmaceuticals for the PET-imaging of prostate cancer. In this connection, we recently developed the fluorine-18-labelled PSMA-ligand [18F]PSMA-1007 as the next generation radiofluorinated Glu-ureido PSMA inhibitor after [18F]DCFPyL and [18F]DCFBC. Since radiosynthesis so far has been suffering from rather poor yields, novel procedures for the automated radiosyntheses of [18F]PSMA-1007 have been developed. We herein report on both the two-step and the novel one-step procedures, which have been performed on different commonly-used radiosynthesisers. Using the novel one-step procedure, the [18F]PSMA-1007 was produced in good radiochemical yields ranging from 25 to 80% and synthesis times of less than 55 min. Furthermore, upscaling to product activities up to 50 GBq per batch was successfully conducted. All batches passed quality control according to European Pharmacopoeia standards. Therefore, we were able to disclose a new, simple and, at the same time, high yielding production pathway for the next generation PSMA radioligand [18F]PSMA-1007. Actually, it turned out that the radiosynthesis is as easily realised as the well-known [18F]FDG synthesis and, thus, transferable to all currently-available radiosynthesisers. Using the new procedures, the clinical daily routine can be sustainably supported in-house even in larger hospitals by a single production batch.

Unusual soft tissue uptake of F-18 sodium fluoride in three patients undergoing F-18 NaF PET/CT bone scans for prostate cancer

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Hawkins, Andrew S.; Howard, Brandon A. [Div. of Nuclear Medicine, Dept. of Radiology, Duke University Medical Center, Durham (United States)

2017-09-15

Three males aged 71 to 80 years with known stage IV metastatic prostate cancer underwent F-18 sodium fluoride (NaF) PET/CT to assess osseous metastatic disease burden and stability. In addition to F-18 NaF avid known osseous metastases, each patient also exhibited increased F-18 NaF activity in soft tissues. The first patient exhibited multiple F-18 NaF avid enlarged retroperitoneal and pelvic lymph nodes on consecutive PET/CT scans. The second patient demonstrated an F-18 NaF avid thyroid nodule on consecutive PET/CT scans. The third patient exhibited increased F-18 NaF activity in a hepatic metastasis.

Radiolabeling and in vitro and in vivo characterization of [18F]FB-[R(8,15,21), L17]-VIP as a PET imaging agent for tumor overexpressed VIP receptors.

Science.gov (United States)

Cheng, Dengfeng; Yin, Duanzhi; Li, Gucai; Wang, Mingwei; Li, Shiqiang; Zheng, Mingqiang; Cai, Hancheng; Wang, Yongxian

2006-12-01

In an effort to develop a peptide-based radiopharmaceutical for the detection of tumors overexpressed vasoactive intestinal peptide receptors with positron emission tomography, we have prepared a novel [R(8,15,21), L17]-VIP peptide for 18F-labeling. This peptide inhibited 125I-VIP binding to rats lung membranes with high affinity [half-maximal inhibitory concentrations (IC50) of 0.12 nm]. Additionally, [R(8,15,21), L17]-VIP showed higher stability than native vasoactive intestinal peptide in vivo of mice. With N-succinimidyl 4-[18F] fluorobenzoate as labeling prosthetic group, [18F]FB-[R(8,15,21), L17]-VIP was obtained in >99% radiochemical purity within 100 min in decay-for-corrected radiochemical yield of 33.6 +/- 3% (n = 5) and a specific radioactivity 255 GBq/micromol at the end of synthesis. Stability of [18F]FB-[R(8,15,21), L17]-VIP in vitro and in vivo were investigated. Biodistribution of this trace was carried out in mice with induced C26 colorectal tumor. Fast clearance of [18F]FB-[R(8,15,21), L17]-VIP from non-target tissues and specific uptakes by tumors realized higher tumor-to-muscle ratio (3.55) and tumor-to-blood ratio (2.37) 60 min postinjection. Clear difference was observed between the blocking and unblocking experiments in biodistribution and whole body radioautography. [18F]FB-[R(8,15,21), L17]-VIP has demonstrated its potential for diagnosing tumors overexpressed vasoactive intestinal peptide receptors both in vitro and in vivo.

New horizons in cardiac innervation imaging. Introduction of novel {sup 18}F-labeled PET tracers

Energy Technology Data Exchange (ETDEWEB)

Kobayashi, Ryohei [University Hospital of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Nihon Medi-Physics Co., Ltd., Research Centre, Chiba (Japan); Chen, Xinyu [University Hospital of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); University Hospital of Wuerzburg, Comprehensive Heart Failure Center, Wuerzburg (Germany); Werner, Rudolf A. [University Hospital of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); University Hospital of Wuerzburg, Comprehensive Heart Failure Center, Wuerzburg (Germany); Johns Hopkins School of Medicine, The Russell H Morgan Department of Radiology and Radiological Sciences, Baltimore, MD (United States); Lapa, Constantin [University Hospital of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Javadi, Mehrbod S. [Johns Hopkins School of Medicine, The Russell H Morgan Department of Radiology and Radiological Sciences, Baltimore, MD (United States); Higuchi, Takahiro [University Hospital of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); University Hospital of Wuerzburg, Comprehensive Heart Failure Center, Wuerzburg (Germany); National Cerebral and Cardiovascular Center, Department of Biomedical Imaging, Research Institute, Suita (Japan)

2017-12-15

Cardiac sympathetic nervous activity can be uniquely visualized by non-invasive radionuclide imaging techniques due to the fast growing and widespread application of nuclear cardiology in the last few years. The norepinephrine analogue {sup 123}I-meta-iodobenzylguanidine ({sup 123}I-MIBG) is a single photon emission computed tomography (SPECT) tracer for the clinical implementation of sympathetic nervous imaging for both diagnosis and prognosis of heart failure. Meanwhile, positron emission tomography (PET) imaging has become increasingly attractive because of its higher spatial and temporal resolution compared to SPECT, which allows regional functional and dynamic kinetic analysis. Nevertheless, wider use of cardiac sympathetic nervous PET imaging is still limited mainly due to the demand of costly on-site cyclotrons, which are required for the production of conventional {sup 11}C-labeled (radiological half-life, 20 min) PET tracers. Most recently, more promising {sup 18}F-labeled (half-life, 110 min) PET radiopharmaceuticals targeting sympathetic nervous system have been introduced. These tracers optimize PET imaging and, by using delivery networks, cost less to produce. In this article, the latest advances of sympathetic nervous imaging using {sup 18}F-labeled radiotracers along with their possible applications are reviewed. (orig.)

{sup 18}F-DOPA PET/CT for assessment of response to induction chemotherapy in a child with high-risk neuroblastoma

Energy Technology Data Exchange (ETDEWEB)

Piccardo, Arnoldo [Galliera Hospital, Nuclear Medicine Unit, Genoa (Italy); E.O. Ospedali Galliera, Department of Nuclear Medicine, Genoa (Italy); Lopci, Egesta [Humanitas Clinical and Research Center, Nuclear Medicine Department, Rozzano, MI (Italy); Foppiani, Luca [Galliera Hospital, Internal Medicine and Endocrinology, Genoa (Italy); Morana, Giovanni [G. Gaslini Children' s Hospital, Department of Pathology and Radiology, Genoa (Italy); Conte, Massimo [G. Gaslini Children' s Hospital, Department of Hematology-Oncology, Genoa (Italy)

2014-03-15

Functional imaging plays a crucial role in the assessment of neuroblastoma. The evaluation of response to induction chemotherapy is a cornerstone in scheduling proper treatment management in patients affected by high-risk neuroblastoma. {sup 123}I-metaiodobenzylguanidine has been recognized as the radiopharmaceutical of choice in neuroblastoma assessment. To date, the clinical role of PET/CT in pediatric malignancy is not well established.{sup 18}F-DOPA-PET/CT has been recently used in neuroblastoma, and compared with {sup 123}I-MIBG-scan. Scant new data are available about the role of this tool in the evaluation of treatment response after induction chemotherapy. We investigate the role of {sup 18}F-DOPA-PET/CT in characterizing the response to induction chemotherapy in a child affected by high-risk-neuroblastoma, in whom the rare association of {sup 123}I-MIBG-negative primary tumor and MIBG-positive bone marrow metastases was observed. (orig.)

Fully automated SPE-based synthesis and purification of 2-[{sup 18}F]fluoroethyl-choline for human use

Energy Technology Data Exchange (ETDEWEB)

Schmaljohann, Joern [Department of Nuclear Medicine, University of Bonn, Bonn (Germany); Department of Nuclear Medicine, University of Aachen, Aachen (Germany); Schirrmacher, Esther [McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec (Canada); Waengler, Bjoern; Waengler, Carmen [Department of Nuclear Medicine, Ludwig-Maximilians University, Munich (Germany); Schirrmacher, Ralf, E-mail: ralf.schirrmacher@mcgill.c [McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, Quebec (Canada); Guhlke, Stefan, E-mail: stefan.guhlke@ukb.uni-bonn.d [Department of Nuclear Medicine, University of Bonn, Bonn (Germany)

2011-02-15

Introduction: 2-[{sup 18}F]Fluoroethyl-choline ([{sup 18}F]FECH) is a promising tracer for the detection of prostate cancer as well as brain tumors with positron emission tomography (PET). [{sup 18}F]FECH is actively transported into mammalian cells, becomes phosphorylated by choline kinase and gets incorporated into the cell membrane after being metabolized to phosphatidylcholine. So far, its synthesis is a two-step procedure involving at least one HPLC purification step. To allow a wider dissemination of this tracer, finding a purification method avoiding HPLC is highly desirable and would result in easier accessibility and more reliable production of [{sup 18}F]FECH. Methods: [{sup 18}F]FECH was synthesized by reaction of 2-bromo-1-[{sup 18}F]fluoroethane ([{sup 18}F]BFE) with dimethylaminoethanol (DMAE) in DMSO. We applied a novel and very reliable work-up procedure for the synthesis of [{sup 18}F]BFE. Based on a combination of three different solid-phase cartridges, the purification of [{sup 18}F]BFE from its precursor 2-bromoethyl-4-nitrobenzenesulfonate (BENos) could be achieved without using HPLC. Following the subsequent reaction of the purified [{sup 18}F]BFE with DMAE, the final product [{sup 18}F]FECH was obtained as a sterile solution by passing the crude reaction mixture through a combination of two CM plus cartridges and a sterile filter. The fully automated synthesis was performed using as well a Raytest SynChrom module (Raytest, Germany) or a Scintomics HotboxIII module (Scintomics, Germany). Results: The radiotracer [{sup 18}F]FECH can be synthesized in reliable radiochemical yields (RCY) of 37{+-}5% (Synchrom module) and 33{+-}5% (Hotbox III unit) in less than 1 h using these two fully automated commercially available synthesis units without HPLC involvement for purification. Detailed quality control of the final injectable [{sup 18}F]FECH solution proved the high radiochemical purity and the absence of Kryptofix2.2.2, DMAE and DMSO used in the

Synthesis of n.c.a. 18F-fluorinated NMDA- and D4-receptor ligands via [18F]fluorobenzenes

International Nuclear Information System (INIS)

Ludwig, T.

2005-11-01

In this thesis new strategies were developed and evaluated for the no-carrier-added (n.c.a.) 18 F-labelling of receptor ligands as radiodiagnostics for characterization of brain receptors using positron-emission-tomography (PET). Special emphasis was placed on the synthesis of n.c.a. (±)-3-(4-hydroxy-4-(4-[ 18 F]fluorophenyl)-piperidin-l-yl)chroman-4,7-diol, a ligand with high affinity for the NR2B subtype of NMDA receptors and n.c.a. (3-(4-[ 18 F]fluorphenoxy)propyl)-(2-(4-tolylphenoxy)ethyl)amine ([ 18 F]FPTEA) a dopamine D 4 receptor ligand. In order to synthesize n.c.a. (±)-3-(4-hydroxy-4-(4-[ 18 F]fluorophenyl)-piperidin-l-yl)chroman-4,7-diol the 18 F-fluoroarylation method via metallorganic intermediates was modified and improved. The suitability of the organometallic 18 F-fluoroarylation agents was proven with several model compounds. High radiochemical yields of 20-30% were obtained also with piperidinone-derivatives. The preparation of a suitable precursor for the synthesis of the NMDA receptor ligand, however, could not be achieved by synthesis of appropriate 1,3-dioxolane protected piperidinone derivatives. Further, the synthesis of n.c.a. ([ 18 F]fluoroaryloxy)alkylamines via n.c.a. 4-[ 18 F]fluorophenol was developed and evaluated. The synthesis of n.c.a. [ 18 F]fluoroarylethers with corresponding model compounds was optimized and led to a radiochemical yield of 25-60%, depending on the alkylhalide used. The preparation of n.c.a. 1-(3-bromopropoxy)-4-[ 18 F]fluorobenzene proved advantageous in comparison to direct use of 4-[ 18 ]fluorophenol for coupling with a corresponding N-protected precursor for the synthesis of n.c.a. [ 18 F]FPTEA. With regard to the radiochemical yields and the loss of activity during the synthesis and isolation of n.c.a. 4-[ 18 F]fluorophenol and n.c.a. 1-(3-bromopropoxy)-4-[ 18 F]fluorobenzene, [ 18 F]FPTEA was obtained by reaction with 2-(4-tolyloxy)ethylamine in radiochemical yields of about 25-30% in ethanol or 2-butanone

Characterization of the materials used in the construction of a physical phantom for calibration of 18F-FDG internal dosimetry system

International Nuclear Information System (INIS)

Vital, Katia D.; Mendes, Bruno M.; Fonseca, Telma C.F.; Silva, Teógenes A. da

2017-01-01

The Internal Dosimetry Laboratory (LDI) of the Nuclear Technology Development Center (CDTN) in Minas Gerais, Brazil, is responsible for the routine monitoring of Occupationally Exposed Individuals (OEIs) to 18 F-FDG and other radiopharmaceuticals produced at CDTN. The monitoring system is usually calibrated using a physical head simulator, since 18 F is usually incorporated into the brain at the time of contamination. However, the geometry of the brain is not adequately represented by the latex pocket, which does not fill the entire volume of the volume skull. In this study, the characterization of the materials regarding the composition, density and attenuation coefficient of the materials used in the production of the new physical head simulator was carried out. An equivalent tissue material containing 97% water, 2.5% agar, 0.5% urea and 8 MBq of 18 F-FDG was produced, the interior of the skull was filled with the material. After solidification, experimental measurements were performed on the NaI(Tl) 3 x 3 s cintillation detector, the density of the simulant material was determined by the flotation method and the attenuation coefficient of the XCOM database software provided by NIST. It was concluded that the PVC skull has acceptable characteristics to simulate a human skull in 18 F-FDG internal dosimetry. The agar gel was shown to be a stable material capable of modeling different geometries and simulating the incorporation of 18 F-FDG into the brain. (author)

Comparison of three 18F-labeled carboxylic acids with 18F-FDG of the differentiation tumor from inflammation in model mice

International Nuclear Information System (INIS)

Wang, Hongliang; Tang, Ganghua; Hu, Kongzhen; Huang, Tingting; Liang, Xiang; Wu, Zhifang; Li, Sijin

2016-01-01

The aim of this study was to compare the properties and feasibility of the glucose analog, 2- 18 F-fluoro-2-deoxy-D-glucose ( 18 F-FDG), three short 18 F-labeled carboxylic acids, 18 F-fluoroacetate ( 18 F-FAC), 2- 18 F-fluoropropionic acid ( 18 F-FPA) and 4-( 18 F)fluorobenzoic acid ( 18 F-FBA), for differentiating tumors from inflammation. Biodistributions of 18 F-FAC, 18 F-FPA and 18 F-FBA were determined on normal Kunming mice, and positron emission tomography (PET) imaging with these tracers were performed on the separate tumor-bearing mice model and inflammation mice model in comparison with 18 F-FDG. Biodistribution results showed that 18 F-FAC and 18 F-FPA had similar biodistribution profiles and the slow radioactivity clearance from most tissues excluding the in vivo defluorination of 18 F-FAC, and 18 F-FBA demonstrated a lower uptake and fast clearance in most tissues. PET imaging with 18 F-FDG, 18 F-FAC and 18 F-FPA revealed the high uptake in both tumor and inflammatory lesions. The ratios of tumor-to-inflammation were 1.63 ± 0.28 for 18 F-FDG, 1.20 ± 0.38 for 18 F-FAC, and 1.41 ± 0.33 for 18 F-FPA at 60 min postinjection, respectively. While clear tumor images with high contrast between tumor and inflammation lesion were observed in 18 F-FBA/PET with the highest ratio of tumor-to-inflammation (1.98 ± 0.15). Our data demonstrated 18 F-FBA is a promising PET probe to distinguish tumor from inflammation. But the further modification of 18 F-FBA structure is required to improve its pharmacokinetics

Preclinical test: bacterial reverse mutation test for {sup 18}F-fluorocholine produced in CDTN

Energy Technology Data Exchange (ETDEWEB)

Mendes, Bruno M.; Bispo, Ana Carolina A.; Campos, Danielle C.; Silva, Juliana B., E-mail: bmm@cdtn.br, E-mail: acab@cdtn.br, E-mail: dcc@cdtn.br, E-mail: silvajb@cdtn.b [Centro de Desenvolvimento da Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil)

2013-07-01

The choline labeled with fluorine-18 (18FCH) is being considered as a great importance radiopharmaceutical due to its effective detection of many type of malignant neoplasm. The research related to {sup 18}F-fluorocholine synthesis in CDTN was initiated in 2010. In order to obtain clinical research approval, as well as to register {sup 18}FCH for marketing, safety and efficacy preclinical testing are required. The present work evaluated the {sup 18}FCH genotoxic potential through the bacterial reverse mutation test (Ames test) using Salmonella typhimurium TA-98, TA-100, TA-1535 and TA-1537 strains and Escherichia coli WP2 uvrA strain. The reverse mutation test in bacteria for fluorcolina was conducted in two stages. Initially the method was applied to 'cold' fluorocholine molecule (19FCH). Subsequently, the decayed product of {sup 18}FCH synthesis was evaluated. The first step was performed in order to examine the FCH molecule mutagenicity. The second was carried out to determine the mutagenic potential of final product. All strains were tested in triplicate for each exposure concentration, in the presence and absence of metabolic activation (S-9 mix - 10%). There were no statistically significant increases in revertant colonies rate for any strains tested after their exposure to decayed {sup 18}FCH or {sup 19}FCH. The number of revertant colonies in positive controls was significantly higher than that observed in significant increases in revertant colonies rate for any strains tested after their exposure to decayed {sup 18}FCH or {sup 19}FCH. The number of revertant colonies in positive controls was significantly higher than that observed in negative controls. Based on results of this assay, {sup 18}FCH and {sup 19}FCH, at tested doses, were found to be non-mutagenic in bacterial reverse mutation test. (author)

Radiation dosimetry estimates of [{sup 18}F]-fluoroacetate based on biodistribution data of rats

Energy Technology Data Exchange (ETDEWEB)

Zhang Jianping [Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032 (China); Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Zhang Yingjian, E-mail: yjzhang111@yahoo.com.cn [Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032 (China); Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Xu Junyan; Yang Zhongyi [Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai 200032 (China); Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032 (China)

2012-01-15

We estimated the dosimetry of [{sup 18}F]fluoroacetate (FAC) with the method established by MIRD based on biodistribution data of rats. We selected some important organs and computed their residence time, their absorbed doses and effective dose with the (%ID{sub Organ}) {sub human} data using OLINDA/EXM 1.1 program. We observed the highest absorbed doses in the heart wall (0.025 mGy/MBq) and the lowest in skin (0.0079 mGy/MBq). The total mean absorbed doses and the effective doses were 0.011 mGy/MBq and 0.014 mSv/MBq, respectively. A 370-MBq injection of FAC leads to an estimated effective dose of 5.2 mSv. The potential radiation risk associated with FAC/PET imaging is well within the accepted limits. - Highlights: Black-Right-Pointing-Pointer We demonstrate a proper model to estimate the absorbed dose and effective dose of normal human. Black-Right-Pointing-Pointer Dosimetry of [{sup 18}F]-Fluoroacetate was estimated in human based on biodistribution of rats. Black-Right-Pointing-Pointer A 370 MBq injection of [{sup 18}F]-Fluoroacetate leads to an estimated effective dose of 5.2 mSv.

Clinical studies of 18F-FDG and 18F-FP-β-CIT PET imaging in hemi-Parkinson's disease

International Nuclear Information System (INIS)

Zhao Jun; Lin Xiangtong; Guan Yihui; Zuo Chuantao; Zhang Zhengwei; Wang Jian; Sun Bomin; Chen Zhengping

2003-01-01

Objective: To study the characteristics of 18 F-fluorodeoxyglucose (FDG) and 18 F-N-3-fluoro-propyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane ( 18 F-FP-β-CIT) PET imaging in patients with hemi-Parkinson's disease (hemi-PD) and to assess their value in early diagnosis. Methods: 34 cases of hemi-PD (Hoehn and Yahr stage I-II) and 16 normal control subjects were selected for this study. 16 patients were performed with 18 F-FDG PET imaging, 18 patients with 18 F-FP-β-CIF, while 6 patients of them both 18 F-FDG and 18 F-FP-β-CIT. 30 min after injection of 185-259 MBq 18 F-FDG, 3D brain scans were acquired. Region of interest (ROI) analysis and statistical parametric mapping (SPM) were applied. 18 F-FP-β-CIT PET imaging was carried out 2-3 h post injection, and (ROI-cerebellum)/cerebellum ratio was calculated. Results: In right hemi-PD, reductions in 18 F-FDG metabolism were observed in the left basal ganglia compared with control group, but with no significant difference (P>0.05). The results of SPM analysis showed that a significant reduction in FDG uptake in the left superior frontal gyrus, middle frontal gyrus, inferior frontal gyrus and left middle temporal gyrus, whereas a significant increase in the bilateral precentral gyrus , superior parietal lobule, left middle occipital gyrus and left thalamus as compared with the control group. There was a significant reduction in 18 F-FP-β-CIT uptake in putamen, its reduction was found not only in the contralateral putamen, but also in the ipsilateral ones, and more pronounced in the contralateral posterior putamen. Conclusions: 18 F-FDG PET imaging is non-specific for the early diagnosis of PD. 18 F-FP-β-CIT PET imaging could find the changes of striatum dopamine transporter at early stage, therefore it was helpful for early diagnosis and differential diagnosis of PD. Combined with 18 F-FDG PET imaging, the changes of local cerebral glucose metabolism in PD could also be evaluated

Radiopharmaceuticals

International Nuclear Information System (INIS)

Ganatra, R.D.

1992-01-01

Today there are an estimated ten million nuclear imaging procedures, performed each year, in just the United States, and the number is still growing. More than 30,000 therapy procedures are performed in the USA each year using radiopharmaceuticals. Moreover, while the numbers continue to grow, so also do the variety of the procedures being employed. A weakness of nuclear medicine is related also to one of its strengths. Unlike other types of imaging where only an instrument and the patient are required (e.g., with ultrasonics); nuclear medicine requires a radiopharmaceutical. At the same time, the variety of radiopharmaceuticals offers the ability to trace one or more particular functions of the human body. This provides nuclear medicine with great variety in detecting specific pathologies. Various nuclear medicine studies are possible because of the localization of radiopharmaceuticals in different organs

Synthetic techniques of radiopharmaceuticals production labeled with C-11 for PET in cardiology

Science.gov (United States)

Dyubkov, V. S.; Ekaeva, I. V.; Katunina, T. A.; Rumyantsev, A. S.; Silchenkov, A. V.; Tuflina, T. V.

2017-01-01

Positron emission tomography (PET) and PET-Computerised Tomography (CT) are unique, non-invasive diagnostic techniques, in which the local, temporal and quantitative distributions of radioactive labelled substances are measured to investigate physiological processes. It is well known that PET centre of Bakulev Scientific Centre for Cardiovascular Surgery is the oldest one in Moscow. During more than fifteen years a large number of patients have received PET scans. Due to main stream of Scientific Centre, emphasis is placed on examining the heart functioning. For the diagnosis innervation of the heart muscle a number of radiopharmaceuticals are used, including PET radiopharmaceuticals such as 11C-CGP 12177, 11C-meta-hydroxyephedrine as well as its synthetic analogues labelled with other PET radionuclides (18F, 68Ga). 11C-meta-hydroxyephedrine is one of the most perspective radiopharmaceutical for an investigation of cardiac receptors function due to required materials availability for a radio synthesis in Russia. The main advantage of proposed 11C-meta-hydroxyephedrine synthesis technique is the use of a catalyst which allows one decrease reaction time from 5 minutes to 30 seconds. Obtained results allow one decrease reaction time of methylation and increase radiochemical and technological yields.

Preparações radiofarmacêuticas e suas aplicações Radiopharmaceuticals and applications

Directory of Open Access Journals (Sweden)

Rita Oliveira

2006-06-01

ármacos em uso clínico corresponde a agentes de perfusão. Atualmente, o esforço de investigação na área da química radiofarmacêutica centra-se no desenvolvimento de radiofármacos específicos que possam fornecer informação, ao nível molecular, relativa às alterações bioquímicas associadas às diferentes patologias.Radiopharmaceuticals are substances without pharmacological activity that are used in Nuclear Medicine for diagnosis and therapy for several diseases. Diagnosis radiopharmaceuticals generally emit gamma radiation or positrons (beta+, because their decay originates penetrating electromagnetic radiation that can cross the tissues and be externally detected. Therapeutic radiopharmaceuticals must include in their composition ionized particles emission nucleus (a, b- or Auger electrons, since their action is based in selective tissue destruction. There are two main methods for image acquisition: SPECT (Single Photon Emission Computerized Tomography that uses g emission radionuclides (99mTc, 123I, 67Ga, 201Tl and PET (Positron Emission Tomography that uses positron emission radionuclides like 11C, 13N, 15O, 18F. Radiopharmaceuticals can be classified into perfusion radiopharmaceuticals (first generation or specific radiopharmaceuticals (second generation. Perfusion radiopharmaceuticals are transported in the blood e reach the target organ in the direct proportion of the blood stream. Specific radiopharmaceuticals contain a biologically active molecule that binds to cellular receptors that must remain biospecific after binding to the radiopharmaceutical. For this type of radiopharmaceuticals, tissue or organ uptake is determined by the biomolecule capacity of recognizing receptors in those biological structures. Radiopharmaceuticals are produced ready to use, in cold kits or in autologal preparations. According to the preparation type there is a different quality control procedure. Most of the radiopharmaceuticals used nowadays are of the perfusion type

Aspects of the production of 18F-2-deoxy-2-fluoro-D-glucose via 18F2 with a tandem Van de Graaf accelerator

International Nuclear Information System (INIS)

Shaughnessy, W.J.; Gatley, S.J.; Hichwa, R.D.; Lieberman, L.M.; Nickles, R.J.

1981-01-01

During deuteron irradiation of 100 psig neon containing 1-2% of elemental fluorine, the induced 18 F partitions into three main fractions. About 50% remains in the passivated nickel target after elution of the gas mixture. Some of the gaseous 18 F is capable of performing fluorination reactions and is presumed to be 18 F 2 : the rest is a mixture of at least two unreactive gases, one of which behaves on gas chromatography like CF 4 . The ratio of reactive to unreactive gaseous 18 F decreases with longer irradiation times but increases when the target gas is cooled to -30C during bombardment. Reaction of the presumed 18 F 2 with 4.5,6-triacetyl-D-glucal, essentially by the published method, yielded 18 F-2-deoxy-2-fluoro-4,5,6-triacetyl-x-D-glucosyl fluoride and the corresponding β-D-mannosyl fluoride. These were separated either by column chromatography or preparative TLC, using plates with a pre-absorbent layer. Hydrolysis of the glucoyl fluoride gave 18 F-2-deoxy-2-fluoro-D-glucose ( 18 F-2FDG) with a decay-corrected yield of about 10% based on 18 F trapped by the triacetylglucal. The 60 min organ distribution of 18 F from 18 F-2-FDG in tumor bearing rats was compared with the corresponding distribution after administration of 18 F-3-deoxy-3-fluoro-D-glucose ( 18 F-3FDG). Organ/blood ratios were uniformly higher for 18 F-2FDG than for no carrier added 18 F-3FDG; only heart, brain and thyroid had ratios greater than unity. Added carrier 3-FDG further lowered organ/blood ratios. The main conclusion drawn from this animal work is that 18 F-3FDG is unlikely to rival 18 F-2FDG for nuclear medicine studies, where high target /blood ratios (obtained by metabolic trapping as the sugar-6-phosphate) are necessary. However 18 F-3FDG may be useful for estimating the concentration of free glucose in organs if further work confirms that it is an essentially non-metabolized analog of glucose. (author)

Radiation dosimetry of [(18)F]VAT in nonhuman primates.

Science.gov (United States)

Karimi, Morvarid; Tu, Zhude; Yue, Xuyi; Zhang, Xiang; Jin, Hongjun; Perlmutter, Joel S; Laforest, Richard

2015-12-01

The objective of this study is to determine the radiation dosimetry of a novel radiotracer for vesicular acetylcholine transporter (-)-(1-((2R,3R)-8-(2-[(18)F]fluoro-ethoxy)-3-hydroxy-1,2,3,4-tetrahydronaphthalen-2-yl)piperidin-4-yl)(4-fluorophenyl)-methanone ([(18)F]VAT) based on PET imaging in nonhuman primates. [(18)F]VAT has potential for investigation of neurological disorders including Alzheimer's disease, Parkinson's disease, and dystonia. Three macaque fascicularis (two males, one female) received 185.4-198.3 MBq [(18)F]VAT prior to whole-body imaging in a MicroPET-F220 scanner. Time activity curves (TACs) were created from regions of interest (ROIs) that encompassed the entire small organs or samples with the highest activity within large organs. Organ residence times were calculated based on the TACs. We then used OLINDA/EXM 1.1 to calculate human radiation dose estimates based on scaled organ residence times. Measurements from directly sampled arterial blood yielded a residence time of 0.30 h in agreement with the residence time of 0.39 h calculated from a PET-generated time activity curve measured in the left ventricle. Organ dosimetry revealed the liver as the critical organ (51.1 and 65.4 μGy/MBq) and an effective dose of 16 and 19 μSv/MBq for male and female, respectively. The macaque biodistribution data showed high retention of [(18)F]VAT in the liver consistent with hepatobiliary clearance. These dosimetry data support that relatively safe doses of [(18)F]VAT can be administered to obtain imaging in humans.