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)

Radiosynthesis and pre-clinical evaluation of [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline

Energy Technology Data Exchange (ETDEWEB)

Smith, Graham [Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Zhao Yongjun [MDx Discovery (part of GE Healthcare) at Hammersmith Imanet, Ltd., Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Leyton, Julius [Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Shan Bo [MDx Discovery (part of GE Healthcare) at Hammersmith Imanet, Ltd., Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Nguyen, Quang-de; Perumal, Meg [Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Turton, David [GE-Imanet, Hammersmith Hospital, Du Cane Road, London, W12 0NN (United Kingdom); Arstad, Erik; Luthra, Sajinder K.; Robins, Edward G. [MDx Discovery (part of GE Healthcare) at Hammersmith Imanet, Ltd., Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom); Aboagye, Eric O., E-mail: eric.aboagye@imperial.ac.u [Comprehensive Cancer Imaging Centre, Faculty of Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London W12 0NN (United Kingdom)

2011-01-15

Introduction: Choline radiotracers are widely used for clinical PET diagnosis in oncology. [{sup 11}C]Choline finds particular utility in the imaging of brain and prostate tumor metabolic status, where 2-[{sup 18}F]fluoro-2-deoxy-D-glucose ('FDG') shows high background uptake. More recently we have extended the clinical utility of [{sup 11}C]choline to breast cancer where radiotracer uptake correlates with tumor aggressiveness (grade). In the present study, a new choline analog, [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline, was synthesized and evaluated as a potential PET imaging probe. Methods: [{sup 18}F]Fluorocholine, [{sup 18}F]fluoro-[1-{sup 2}H{sub 2}]choline and [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline were synthesized by alkylation of the relevant precursor with [{sup 18}F]fluorobromomethane or [{sup 18}F]fluoromethyl tosylate. Radiosynthesis of [{sup 18}F]fluoromethyl tosylate required extensive modification of the existing method. [{sup 18}F]Fluorocholine and [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline were then subjected to in vitro oxidative stability analysis in a chemical oxidation model using potassium permanganate and an enzymatic model using choline oxidase. The two radiotracers, together with the corresponding di-deuterated compound, [{sup 18}F]fluoro-[1-{sup 2}H{sub 2}]choline, were then evaluated in vivo in a time-course biodistribution study in HCT-116 tumor-bearing mice. Results: Alkylation with [{sup 18}F]fluoromethyl tosylate proved to be the most reliable radiosynthetic route. Stability models indicate that [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline possesses increased chemical and enzymatic (choline oxidase) oxidative stability relative to [{sup 18}F]fluorocholine. The distribution of the three radiotracers, [{sup 18}F]fluorocholine, [{sup 18}F]fluoro-[1-{sup 2}H{sub 2}]choline and [{sup 18}F]fluoro-[1,2-{sup 2}H{sub 4}]choline, showed a similar uptake profile in most organs. Crucially, tumor uptake of [{sup 18}F]fluoro

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)

Synthesis of no-carrier-added fluorine-18 2-fluoro-2-deoxy-d-glucose

International Nuclear Information System (INIS)

Tewson, T.J.

1983-01-01

A new synthetic procedure for the preparation of fluorine-18 2-fluoro-2-deoxy-glucose has been developed. This procedure offers the advantages of flexibility in the source of the fluorine-18, high yields, and short synthesis times. The procedure works at the no-carrier-added level and gives a product of very high specific activity

Cryptand [2.2.2]quantitation in the synthesis of 2-[fluorine-18]fluoro-2-deoxy-d-glucose

International Nuclear Information System (INIS)

Kothari, P.J.; Ginos, J.; Finn, R.D.; Larson, S.M.; Link, J.M.; Krohn, K.A.; Garmestani, K.

1992-01-01

Most automated synthetic devices for the preparation of [ 18 F]2-fluoro-2-deoxy-D-glucose ([ 18 F]FDG) employ cryptand [2.2.2](4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo(8.8.8)-hexacosane) to facilitate the 18 F displacement reaction. Lack of simple spectroscopic and/or chromatographic determinations for cryptands prompted our investigation with tritiated [2.2.2] cryptand reagent to determine the absolute concentration of this reagent throughout the synthetic procedure leading to the final formulation. The concentration of cryptand [2.2.2] in the final formulation has been determined to range from 0.39 μg/ml to 0.60 μg/ml which is well below the detection limit by a method recently reported. (author) 1 fig., 1 tab., 5 refs

1H NMR study of 2-deoxy-D-arabino-hexopyranose (2-deoxy-glucopyranose), 2-deoxy-D-lyxo-hexopyranose (2-deoxy-galactopyranose) and 2'-deoxy lactose

International Nuclear Information System (INIS)

Bruyn, A. de; Anteunis, M.

1975-01-01

Complete analyses of the 1 H n.m.r. spectra at 300 MHz of D 2 O solutions of 2-deoxy-D-arabino-hexopyranose, 2-deoxy-D-lyxo-hexopyranose and 2'-deoxy lactose. Chemical shifts in the deoxy monosaccharides and in 2'-deoxy lactose. Chemical shifts in the deoxy monosaccharides and in 2'-deoxy lactose are compared with those previously obtained in the parent aldeohexopyranoses, glucobioses and D-galactopyranosol-D-glucoses. Increment values are suggested in order to predict chemical shifts in 2-deoxy derivatives from the well known rules for aldohexopyranoses. (author)

Prognostic value of interim FDG-PET in Hodgkin lymphoma : systematic review and meta-analysis

NARCIS (Netherlands)

Adams, Hugo J A; Nievelstein, Rutger A J; Kwee, Thomas C.

2015-01-01

This study aimed to systematically review and meta-analyse the value of interim (18) F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) in predicting treatment failure in Hodgkin lymphoma. MEDLINE was systematically searched for original studies that used standardized international

Long-term survival of 42 patients with resected N2 non-small-cell lung cancer: the impact of 2-(18)F-fluoro-2-deoxy-D-glucose positron emission tomogram mediastinal staging.

Science.gov (United States)

Barnett, Stephen; Baste, Jean-Marc; Murugappan, Kowsi; Tog, Check; Berlangieri, Salvatore; Scott, Andrew; Seevanayagam, Siven; Knight, Simon

2011-01-01

Prognostic information known preoperatively allows stratification of patients to surgery; induction therapy and surgery; or definitive chemoradiotherapy and may prevent a futile thoracotomy. Attention has focussed on the standard uptake value (SUV) of the primary tumour but less has been described regarding the 18F-fluoro-2-deoxy-D-glucose (18F-FDG) avidity of mediastinal nodes. We aimed, in a group of surgically resected cN0-1 but pN2 tumours, to compare the survival of patients with and without 18F-FDG avid mediastinal nodes. Retrospective review of a surgical database identified cN0-1 non-small-cell lung cancer (NSCLC) patients with pN2 disease after resection. Survival of non-FDG avid N2 versus FDG avid N2 groups was compared after stratification according to variables found on univariate analysis to affect survival. From January 1993 to December 2006, 42 patients were identified; 27 (64%) had non-FDG avid N2 disease. Five-year and median survival were better in the non-FDG avid N2 disease group, 25% versus 0% and 30 (16-44) versus 13 (10-16) months, respectively (p=0.02). After 1998, the difference in survival was 41% versus 0% and 35 (14-56) versus 12 (16-18) months, respectively (p=0.02). After resection, patients with non-FDG avid N2 disease have better survival than patients with FDG avid N2 disease. Exploratory thoracotomy alone (after frozen section analysis) cannot be advocated in patients with non-FDG avid N2 disease as survival after resection appears at least equivalent to alternate therapeutic approaches in this group. This assertion may be tempered if right pneumonectomy is required or R0 resection is unachievable. Mediastinal nodal avidity may improve stratification in future studies of long-term survival in NSCLC. Crown Copyright © 2010. Published by Elsevier B.V. All rights reserved.

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

Energy Technology Data Exchange (ETDEWEB)

Shaughnessy, W J; Gatley, S J; Hichwa, R D; Lieberman, L M; Nickles, R J [Wisconsin Univ., Madison (USA). Dept. of Radiology

1981-01-01

During deuteron irradiation of 100 psig neon containing 1-2% of elemental fluorine, the induced /sup 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 /sup 18/F is capable of performing fluorination reactions and is presumed to be /sup 18/F/sub 2/: the rest is a mixture of at least two unreactive gases, one of which behaves on gas chromatography like CF/sub 4/. The ratio of reactive to unreactive gaseous /sup 18/F decreases with longer irradiation times but increases when the target gas is cooled to -30C during bombardment. Reaction of the presumed /sup 18/F/sub 2/ with 4.5,6-triacetyl-D-glucal, essentially by the published method, yielded /sup 18/F-2-deoxy-2-fluoro-4,5,6-triacetyl-x-D-glucosyl fluoride and the corresponding ..beta..-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 /sup 18/F-2-deoxy-2-fluoro-D-glucose (/sup 18/F-2FDG) with a decay-corrected yield of about 10% based on /sup 18/F trapped by the triacetylglucal. The 60 min organ distribution of /sup 18/F from /sup 18/F-2-FDG in tumor bearing rats was compared with the corresponding distribution after administration of /sup 18/F-3-deoxy-3-fluoro-D-glucose (/sup 18/F-3FDG). Organ/blood ratios were uniformly higher for /sup 18/F-2FDG than for no carrier added /sup 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 /sup 18/F-3FDG is unlikely to rival /sup 18/F-2FDG for nuclear medicine studies, where high target /blood ratios (obtained by metabolic trapping as the sugar-6-phosphate) are necessary. However /sup 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

/sup 1/H NMR study of 2-deoxy-D-arabino-hexopyranose (2-deoxy-glucopyranose), 2-deoxy-D-lyxo-hexopyranose (2-deoxy-galactopyranose) and 2'-deoxy lactose. Shift increment studies in 2-deoxy carbohydrates

Energy Technology Data Exchange (ETDEWEB)

de Bruyn, A; Anteunis, M [Ghent Rijksuniversiteit (Belgium)

1975-01-01

Complete analyses are given of the /sup 1/H n.m.r. spectra at 300 MHz of D/sub 2/O solutions of 2-deoxy-D-arabino-hexopyranose, 2-deoxy-D-lyxo-hexopyranose and 2'-deoxy lactose. Chemical shifts in the deoxy monosaccharides and in 2'-deoxy lactose are compared with those previously obtained in the parent aldeohexopyranoses, glucobioses and D-galactopyranosol-D-glucoses. Increment values are suggested in order to predict chemical shifts in 2-deoxy derivatives from the well known rules for aldohexopyranoses.

Microwave-assisted one-pot radiosynthesis of 2′-deoxy-2′-[18F]fluoro-5-methyl-1-β-D-arabinofuranosyluracil ([18F]-FMAU)

International Nuclear Information System (INIS)

Chen, Kai; Li Zibo; Conti, Peter S.

2012-01-01

Objectives: [ 18 F]-FMAU is a PET tracer being evaluated for imaging cell proliferation. Current multi-step procedures of [ 18 F]-FMAU synthesis are time-consuming, resulting in low radiochemical yield and inconvenient applications for the clinic. We have previously reported the use of Friedel-Crafts catalysts for an improved synthesis of [ 18 F]-FMAU. In this study, we investigated the efficiency of microwave-assisted radiosynthesis of [ 18 F]-FMAU in comparison with conventional thermal conditions. Methods: A simplified one-pot synthesis of [ 18 F]-FMAU was developed under microwave conditions. Various reaction times, temperatures, and microwave powers were systematically explored to optimize the coupling reaction of 2-deoxy-2-[ 18 F]fluoro-1,3,5-tri-O-benzoyl-D-arabinofuranose ([ 18 F]-sugar) and bis-2,4-(trimethylsilyloxy)-5-methyluracil (silylated uracil) in the presence of a Friedel-Crafts catalyst, trimethylsilyl trifluoromethanesulfonate (TMSOTf). Results: Microwave significantly enhanced the coupling efficiency of [ 18 F]-sugar and silylated uracil by reducing the reaction time to 10 min (6-fold reduction as compared to conventional heating) at 95 °C. Base hydrolysis followed by high-performance liquid chromatography purification produced the desired [ 18 F]-FMAU. The overall radiochemical yield was 20 ± 4% (decay corrected, n = 3). Radiochemical purity was > 99% and specific activity was > 400 mCi/μmol. The α/β anomer ratio was 1:2. The radiosynthesis time was about 90 min from the end of bombardment. Conclusions: A reliable microwave-assisted approach has been developed for routine synthesis of [ 18 F]-FMAU. The new approach affords a simplified process with shorter synthesis time and higher radiochemical yield as compared to conventional heating. A fully automated microwave-assisted synthesis of [ 18 F]-FMAU can be readily achieved under new reaction conditions.

Prognostic value of interim FDG-PET in R-CHOP-treated diffuse large B-cell lymphoma : Systematic review and meta-analysis

NARCIS (Netherlands)

Adams, Hugo J A; Kwee, Thomas C.

2016-01-01

This study aimed to systematically review and meta-analyze the prognostic value of interim 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone

2-deoxy-2[F-18]fluoro-D-mannose positron emission tomography imaging in atherosclerosis

NARCIS (Netherlands)

Tahara, Nobuhiro; Mukherjee, Jogeshwar; de Haas, Hans J; Petrov, Artiom D; Tawakol, Ahmed; Haider, Nezam; Tahara, Atsuko; Constantinescu, Cristian C; Zhou, Jun; Boersma, Hendrikus H; Imaizumi, Tsutomu; Nakano, Masataka; Finn, Aloke; Fayad, Zahi; Virmani, Renu; Fuster, Valentin; Bosca, Lisardo; Narula, Jagat

Progressive inflammation in atherosclerotic plaques is associated with increasing risk of plaque rupture. Molecular imaging of activated macrophages with 2-deoxy-2[F-18]fluoro-D-glucose ([F-18]FDG) has been proposed for identification of patients at higher risk for acute vascular events. Because

Positron emission tomography with 2-[18F]-Fluoro-2-Deoxy-D-Glucose for initial staging of hodgkin lymphoma: a single center experience in Brazil

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Juliano Julio Cerci

2009-06-01

Full Text Available BACKGROUND: 2-[18F]-Fluoro-2-Deoxy-D-Glucose (FDG-PET is a well established functional imaging modality for the initial staging of Hodgkin lymphoma (HL in patients from Western Europe and North America. The reliability of FDG-PET in populations of different ethnic groups is unclear, as all investigations published to date have come from developed countries. PURPOSE: The aim of the present study was to investigate the effectiveness of FDG-PET in the initial staging of HL patients in a Brazilian population. METHODS: Eighty-two patients with newly diagnosed HL were prospectively included in the study. All patients were staged with both conventional clinical staging (CCS methods, including computed tomography (CT and whole-body FDG-PET methods. A standard of reference for the nodal regions and the extranodal organs was determined using all available information, including the CCS methods, FDG-PET, the diagnostic histology and the follow-up examinations. The results of the CCS were then compared to the FDG-PET results. RESULTS: The sensitivity of FDG-PET was higher for nodal staging than that of CT (87.8% vs. 61.6%, respectively. FDG-PET was also more sensitive than CT in regard to evaluating the extranodal organs for lymphomatous involvement (96.2% vs. 40.0%, respectively. FDG-PET detected all 16 patients who were characterized by a positive bone marrow biopsy and identified an additional 4 patients with bone marrow disease. The incorporation of FDG-PET coupled with CCS in the staging procedure upstaged 20% (17/82 of the patients and downstaged 11% (9/82 of the patients. As a result of these changes in staging, 15% (13/82 of the patients would have received a different therapeutic regimen. CONCLUSIONS: The FDG-PET method is superior to CT for the detection of nodal and extra-nodal HL. The observation that the FDG-PET method upstaged the disease was the most common result (20% of patients brought about by the addition of PET to the staging algorithm

Ion chromatographic analysis of high specific activity 18FDG preparations and detection of the chemical impurity 2-deoxy-2-chloro-D-glucose

International Nuclear Information System (INIS)

Alexoff, D.L.; Casati, R.; Fowler, J.S.; Wolf, A.P.; Shea, C.; Schlyer, D.J.; Chyng-Yann Shiue

1992-01-01

Because of the widespread use of 2-deoxy-2-[ 18 F]fluoro-D-glucose(FDG) prepared by the ''Julich'' method or its variants it was decided necessary to determine the major chemical impurities present in the final product. An analytical system for quantifying FDG was developed using pulsed amperometry after separation by high-performance anion exchange chromotography. With this system a heretofore unidentified impurity, 2-deoxy-2-chloro-D-glucose(C1DG) was found in our preparation and in those from other laboratories using the ''Julich'' method. C1DG arises from C1 - ion displacement during the labeling procedure where C1 - ion comes from several sources, and C1 - ion displacement from the HC1 used in the hydrolysis step. FDG mass was present in the same preparations at a level of ca 1-40 μg. Other major chemical constituents were glucose (ca 1-6 mg) and mannose (ca 10-18 μg). Glycerol, arising from sterilizing filters, was also detected in most preparations. Although C1DG is a chemical impurity which has not been detected previously in nca FDG preparations, its biochemical and pharmacological properties are similar to FDG and 2-deoxy-D-glucose. Thus it is unlikely that the presence of small quantities of C1DG found in typical FDG preparations (ca 100 μg) would have adverse pharmacological or toxicological consequences that would limit continued application of this radiopharmaceutical in basic and clinical studies. (Author)

Transient toxicity of 2-Deoxy-2-[18F] fluoro-D-Glucose in mammalian cells: concise communication

International Nuclear Information System (INIS)

Kassis, A.I.; Adelstein, S.J.; Wolf, A.P.; Fowler, J.G.; Shiue, C.Y.

1983-01-01

The kinetics of uptake and toxicity of the positron emitter F-18 have been examined in a cultured cell line. 2-Deoxy-2[ 18 F]fluoro-D-glucose ( 18 FDG) concentrated rapidly within Chinese hamster V79 cells, and the uptake was linear with the extracellular radioactive concentrations. Whereas 18 FDG sythesized 2 hr before the incubation did not appear to be toxic, that synthesized 5 hr previously was highly toxic. Toxicity was transient and independent of both the extracellular/intracellular radioactive concentration and the energy released from the decay of fluorine-18. Similarly synthesized nonradioactive FDG and Na 18 F were not toxic under comparable experimental conditions. The authors conclude that this transient toxicity is due to an unidentified chemical species that is cytocidal following intracellular localization. These toxic levels are not likely to be achieved in the clinical use of 18 FDG due to dilution factors that are orders of magnitude greater than those used in these in vitro studies

A phase I study on stereotactic body radiotherapy of liver metastases based on functional treatment planning using positron emission tomography with 2-[(18)F]fluoro-2-deoxy-d-galactose

DEFF Research Database (Denmark)

Fode, Mette Marie; Bak-Fredslund, Kirstine; Petersen, Jørgen Baltzer

2017-01-01

BACKGROUND AND PURPOSE: The galactose analog 2-[18F]fluoro-2-deoxy-d-galactose (FDGal) is used for quantification of regional hepatic metabolic capacity by functional positron emission tomography computerized tomography (PET/CT). In the present study, FDGal PET/CT was used for functional treatment...... planning (FTP) of stereotactic body radiotherapy (SBRT) of liver metastases with the aim of minimizing radiation dose to the best functioning liver tissue. MATERIAL AND METHODS: Fourteen patients referred for SBRT had FDGal PET/CT performed before and one month after the treatment. The planning CT...... and the FDGal PET/CT images were deformable co-registered. RESULTS: A reduction in the mean dose of approximately 2 Gy to the best functioning sub-volumes was obtained. One patient developed grade 2 acute morbidity and no patients experienced grade 3 or higher acute morbidities. The regional hepatic metabolic...

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)

Modular automation in PET tracer manufacturing: application of an autosynthesizer to the production of 2-deoxy-2-[18F] fluoro-D-glucose

International Nuclear Information System (INIS)

Alexoff, D.L.; Russell, J.A.G.; Shiue, C.Y.; Wolf, A.P.; Fowler, J.S.; MacGregor, R.R.

1986-01-01

A compact autosynthesizer was developed and used successfully for the production of 2-deoxy-2-[ 18 F]fluoro-D-glucose [ 18 FDG] from gaseous acetyl hypo[ 18 F]fluorite. The autosynthesizer performs a sequence of general purpose synthesis procedures named Synthesis Unit Operations (SUOs). Each SUO is controlled through execution of a digital control algorithm with a BASIC language subroutine. This automatic synthesis system is based on two industry standard microcomputer architectures, the IBM PC and STD Bus, and it becomes a component of an evolving distributed microprocessor network of task-dedicated subsystems suitable for automated manufacturing of several useful radiotracers. The yield of 18 FDG product using the autosynthesizer and remote manually controlled purification procedures is approx. 20% EOB. Radiochemical purity of this product as measured by thin layer chromatography was 96-99%. Chemical purity of the product was measured to be approx. 96%. 2-Deoxy-2-fluoro-D-mannose impurity from this method was determined to be approx. 4%. (author)

Chemical consequences resulting from multi-millicurie preparation of 6-[18F]-fluoro-6-deoxy-L-ascorbic acid

International Nuclear Information System (INIS)

Kothari, P.J.; Finn, R.D.; Bornmann, W.G.; Agus, D.B.; Vera, J.C.; Larson, S.M.

1997-01-01

Ascorbic acid is required for human physiology and is particularly important in maintaining normal connective tissue and host defense. Our interest in this carboxylic acid stems from its similarity in transport with glucose in human cells. In order to investigate these phenomena, we report a refined synthesis of 6-[ 18 F]-fluoro-6-deoxy-L-ascorbic acid ( 18 F-FAA) via nucleophilic displacement of the cyclic sulfate with Kryptofix 2.2.2/K 18 F complex which results in multi-millicurie quantities of high specific activity product. The trace carrier-added synthesis has resulted in a decay corrected radiochemical yield of 31.6±3.4% with a specific activity approaching 180 mCi/μmol. Our preliminary experience with the assessment of the chemical stability of both the radiolabelled and stable product is also presented. (orig.)

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

Dual time point 2-deoxy-2-[18F]fluoro-D-glucose PET/CT: nodal staging in locally advanced breast cancer.

Science.gov (United States)

García Vicente, A M; Soriano Castrejón, A; Cruz Mora, M Á; Ortega Ruiperez, C; Espinosa Aunión, R; León Martín, A; González Ageitos, A; Van Gómez López, O

2014-01-01

To assess dual time point 2-deoxy-2-[(18)F]fluoro-D-glucose (18)(F)FDG PET-CT accuracy in nodal staging and in detection of extra-axillary involvement. Dual time point [(18)F] FDG PET/CT scan was performed in 75 patients. Visual and semiquantitative assessment of lymph nodes was performed. Semiquantitative measurement of SUV and ROC-analysis were carried out to calculate SUV(max) cut-off value with the best diagnostic performance. Axillary and extra-axillary lymph node chains were evaluated. Sensitivity and specificity of visual assessment was 87.3% and 75%, respectively. SUV(max) values with the best sensitivity were 0.90 and 0.95 for early and delayed PET, respectively. SUV(max) values with the best specificity were 1.95 and 2.75, respectively. Extra-axillary lymph node involvement was detected in 26.7%. FDG PET/CT detected extra-axillary lymph node involvement in one-fourth of the patients. Semiquantitative lymph node analysis did not show any advantage over the visual evaluation. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

Radiosynthesis of F-18 labeled cytidine analog 2'-fluoro-5-iodo-l-β-D-arabinofuranosylcytosine ([18F]FIAC)

International Nuclear Information System (INIS)

Wu, C.-Y.; Chan, P.-C.; Chang, W.-T.; Liu, R.-S.; Alauddin, Mian M.; Wang, H-E.

2009-01-01

We reported the synthesis of 2'-deoxy-2'-[ 18 F]fluoro-5-iodo-1-β-D-arabinofuranosyl-5-iodo-cytosine ([ 18 F]FIAC) with 15-20% radiochemical yield (decay corrected) in 3.5 h. 2-deoxy-2-[ 18 F]fluoro-1,3,5-tri-O-benzoyl-α-D-arabinofuranose was prepared following literature procedures with some modifications (yield>70%). The 18 F-fluorosugar was converted to 1-bromo- 18 F-fluorosugar, and then coupled with 5-iodocytocine silyl ether. A mixture of acetonitrile (ACN) and 1,2-dichloroethane (DCE) were employed to achieve optimum radiochemical yield and acceptable β-anomer selectivity (α/β=1/3). After hydrolyzed with sodium methoxide, the crude product was purified using HPLC to afford the β-[ 18 F]FIAC with high radiochemical purity (≥98%).

Tritiated 2-deoxy-D-glucose as a probe for cell membrane permeability studies

International Nuclear Information System (INIS)

Walum, E.; Peterson, A.

1982-01-01

Tritiated 2-deoxy-D-glucose was taken up and phosphorylated by cultured cells of neuronal (NIE 115), glial (138 MG), muscle (L 6) and liver (BRL 123) origin. Upon perfusion the cells slowly released 2-deoxy-D-glucose 6-phosphate. The following values for rate constants, half-lives, and activation energies for the efflux were obtained: NIE 115: 0.0048 min -1 , 143 min, and 72 kJ mol -1 ; 138 MG: 0.0013 min -1 , 547 min, and 85 kJ mol -1 ; L 6: 0.0022 min -1 , 311 min, and 60 kJ mol -1 ; and BRL 123: 0.0013 min -1 , 528 min and 63 kJ mol -1 . When the cultures were perfused with buffer containing Triton X-100 a time- and concentration-dependent increase in the rate of efflux of 2-deoxy-D-glucose 6-phosphate was obtained. It is suggested that 2-deoxy-D-[ 3 H]glucose can be used as a probe in studies of general cell membrane permeability changes

The functional neuroanatomy of verbal memory in Alzheimer's disease: [18F]-Fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) correlates of recency and recognition memory.

Science.gov (United States)

Staffaroni, Adam M; Melrose, Rebecca J; Leskin, Lorraine P; Riskin-Jones, Hannah; Harwood, Dylan; Mandelkern, Mark; Sultzer, David L

2017-09-01

The objective of this study was to distinguish the functional neuroanatomy of verbal learning and recognition in Alzheimer's disease (AD) using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Word Learning task. In 81 Veterans diagnosed with dementia due to AD, we conducted a cluster-based correlation analysis to assess the relationships between recency and recognition memory scores from the CERAD Word Learning Task and cortical metabolic activity measured using [ 18 F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). AD patients (Mini-Mental State Examination, MMSE mean = 20.2) performed significantly better on the recall of recency items during learning trials than of primacy and middle items. Recency memory was associated with cerebral metabolism in the left middle and inferior temporal gyri and left fusiform gyrus (p recognition memory was correlated with metabolic activity in two clusters: (a) a large cluster that included the left hippocampus, parahippocampal gyrus, entorhinal cortex, anterior temporal lobe, and inferior and middle temporal gyri; (b) the bilateral orbitofrontal cortices (OFC). The present study further informs our understanding of the disparate functional neuroanatomy of recency memory and recognition memory in AD. We anticipated that the recency effect would be relatively preserved and associated with temporoparietal brain regions implicated in short-term verbal memory, while recognition memory would be associated with the medial temporal lobe and possibly the OFC. Consistent with our a priori hypotheses, list learning in our AD sample was characterized by a reduced primacy effect and a relatively spared recency effect; however, recency memory was associated with cerebral metabolism in inferior and lateral temporal regions associated with the semantic memory network, rather than regions associated with short-term verbal memory. The correlates of recognition memory included the medial temporal lobe

Radiation and chemical stability of 2-deoxy-2-[18F]fluoro-D-glucose radiopharmaceutical

International Nuclear Information System (INIS)

Buriova, M.

2004-07-01

Qualitative and quantitative analytical technique of low-molecular components of chemical and radiation-chemical decomposition of 2-deoxy-2-[ 18 F]fluoro-D-glucose, 2-[ 18 F]FDG radiopharmaceutical was developed for its extended QC by HPLC with mass-spectrometric electro-spray ionisation detector (ESI MS). The analysis constituted from the LC on silica gel NH 2 bonded column combined with MS, UV-VIS, refraction index and radiometric detectors, and TLC on silica gel and high-performance TLC (HPTLC) on silica gel NH 2 bonded as at the LC column. Condition of analysis, the composition of mobile phase at HPLC and the regime of ESI MS were optimised on the maximal intensity of the signals of analytes, which were predicted for commercial 2-[ 18 F]FDG and its decomposition products. A modern LC/MS system was demonstrated to be suitable not only for identification of unknown analytes, but also for complex analysis of solutes except [ 18 F]F - . This was advantageous for the 2-[ 18 F]FDG autoradiolysis assessment about which no data were published. For comparative purposes, were used a classic TLC on silica gel with mobile phase acetonitrile: water at 95:5 v/v, and HPTLC on NH 2 modified silica gel like the LC column. Mobile phase was identical as by LC/MS method (acetonitrile: 4 mM aqueous solution of ammonium formate 80:20 v/v). Retention times of reference samples: fluorodeoxyglucose, glucose, mannose, arabinose, deoxyglucose, gluconic and glucuronic acids at HPLC were established. Equal composition of the inlet sample and mobile phase was found important to avoid increased background of the MS detector and asymmetry of the chromatographic peaks. Reference substance detectability was investigated for various detectors. Characteristic ions were established for the analytes under consideration. Optimal performance of the ESI MS detector was discovered in negative ions mode or single ion monitoring (SIM) regime. The most intensive signal was observed for all analyte

2-[{sup 18}F]fluoro-2-deoxy-D-glucose positron emission tomography (F.D.G.-PET) can identify chronic lymphocytic leukaemia (C.L.L.) stage A et stage B patients; La tomographie par emission de positons au 2-[{sup 18}F] fluoro-2-desoxy-D-glucose (TEP-FDG) permet d'identifier les stades A et B des leucemies lymphoides chroniques (LLC)

Energy Technology Data Exchange (ETDEWEB)

Berthelot, C.; Vervueren, L.; Le Jeune, J.J.; Couturier, O. [Centre Hospitalier Universitaire, Service de Medecine Nucleaire, 49 - Angers (France); Truchan-Graczyk, M.; Genevieve, F.; Ifrah, N. [Centre Hospitalier Universitaire, Service d' Hematologie, 49 - Angers (France); Poirier, A.L. [BEC, centre Paul-Papin, 49 -Angers (France); Artur-Guillemette, P. [Centre Hospitalier Universitaire, Service de Radiologie, 49 - Angers (France)

2009-09-15

Purpose: There is no data in the literature concerning the utility of 2-[{sup 18}F]fluoro-2-deoxy-d-glucose positron emission tomography (F.D.G.-PET) in chronic lymphocytic leukaemia (C.L.L.), except for the diagnosis of Richter's transformations. The purpose of this study was to assess the potential role of F.D.G.-PET in C.L.L. stages A and B. Materials and methods Thirty-five patients (61 {+-} 9 years; 11 women, 24 men; 8 B and 27 A) have benefited of a F.D.G.-PET scan at baseline, for example, before an eventual treatment. F.D.G.-PET scans were analyzed visually and the maximum values of the Standardised Uptake Value (S.U.V.{sub max}) were measured in the main lymph nodes areas. The ability of F.D.G.-PET to differentiate stages A and B patients was evaluated by Student's tests and Receiver Operating Characteristics (R.O.C.) analysis. Results All patients with a normal F.D.G.-PET (n = 18) were stages A. The remaining 17 patients (9 A and 8 B) showed hyper metabolisms in nodal areas above (n = 17) and below (n = 9) the diaphragm, and no visceral involvement. The lymph nodes hyper metabolisms were always bilateral, and of low intensity (= mediastinum; 9 A), or of higher intensity (= liver, 8 B). The S.U.V.{sub max} of stage B (n = 8) were significantly higher than those of the 27 stages A, in all lymph nodes areas except in mediastinum. The highest intensity of F.D.G. uptake was observed in axillary area in stages B patients (S.U.V.max = 2.74 {+-} 1.03). An axillary S.U.V.{sub max} of 1.33 is the most suitable value for the discrimination between stages A and B patients (R.O.C.; AUC = 0.968; sensitivity 1.00; specificity 0.91). Conclusion Lymph nodes hyper metabolisms are constant in the B stage, and more intense than in stage A. These anomalies are always bilateral, unlike what is observed in Richter's transformation. The intensity of axillary lymph nodes F.D.G. uptake can distinguish C.L.L. stages A and B. (authors)

Radiosynthesis of F-18 labeled cytidine analog 2'-fluoro-5-iodo-l-{beta}-D-arabinofuranosylcytosine ([{sup 18}F]FIAC)

Energy Technology Data Exchange (ETDEWEB)

Wu, C.-Y.; Chan, P.-C.; Chang, W.-T. [Institute of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, 155, Li-Nong Street, Sector 2, Bei-tou, Taipei 112, Taiwan (China); Liu, R.-S. [Department of Nuclear Medicine, Faculty of Medicine, National Yang-Ming University, Taiwan (China); Department of Nuclear Medicine and National PET/Cyclotron Center, Taipei Veterans General Hospital, Taiwan (China); Alauddin, Mian M. [Department of Experimental Diagnostic Imagiing, MD Anderson Cancer Center, University of Texas (United States); Wang, H-E. [Institute of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, 155, Li-Nong Street, Sector 2, Bei-tou, Taipei 112, Taiwan (China)], E-mail: hewang@ym.edu.tw

2009-07-15

We reported the synthesis of 2'-deoxy-2'-[{sup 18}F]fluoro-5-iodo-1-{beta}-D-arabinofuranosyl-5-iodo-cytosine ([{sup 18}F]FIAC) with 15-20% radiochemical yield (decay corrected) in 3.5 h. 2-deoxy-2-[{sup 18}F]fluoro-1,3,5-tri-O-benzoyl-{alpha}-D-arabinofuranose was prepared following literature procedures with some modifications (yield>70%). The {sup 18}F-fluorosugar was converted to 1-bromo-{sup 18}F-fluorosugar, and then coupled with 5-iodocytocine silyl ether. A mixture of acetonitrile (ACN) and 1,2-dichloroethane (DCE) were employed to achieve optimum radiochemical yield and acceptable {beta}-anomer selectivity ({alpha}/{beta}=1/3). After hydrolyzed with sodium methoxide, the crude product was purified using HPLC to afford the {beta}-[{sup 18}F]FIAC with high radiochemical purity ({>=}98%)

Lung inhomogeneities, inflation and [18F]2-fluoro-2-deoxy-D-glucose uptake rate in acute respiratory distress syndrome.

Science.gov (United States)

Cressoni, Massimo; Chiumello, Davide; Chiurazzi, Chiara; Brioni, Matteo; Algieri, Ilaria; Gotti, Miriam; Nikolla, Klodiana; Massari, Dario; Cammaroto, Antonio; Colombo, Andrea; Cadringher, Paolo; Carlesso, Eleonora; Benti, Riccardo; Casati, Rosangela; Zito, Felicia; Gattinoni, Luciano

2016-01-01

The aim of the study was to determine the size and location of homogeneous inflamed/noninflamed and inhomogeneous inflamed/noninflamed lung compartments and their association with acute respiratory distress syndrome (ARDS) severity.In total, 20 ARDS patients underwent 5 and 45 cmH2O computed tomography (CT) scans to measure lung recruitability. [(18)F]2-fluoro-2-deoxy-d-glucose ([(18)F]FDG) uptake and lung inhomogeneities were quantified with a positron emission tomography-CT scan at 10 cmH2O. We defined four compartments with normal/abnormal [(18)F]FDG uptake and lung homogeneity.The homogeneous compartment with normal [(18)F]FDG uptake was primarily composed of well-inflated tissue (80±16%), double-sized in nondependent lung (32±27% versus 16±17%, pinflation and [(18)F]FDG uptake decreases with ARDS severity, while the inhomogeneous poorly/not inflated compartment increases. Most of the lung inhomogeneities are inflamed. A minor fraction of healthy tissue remains in severe ARDS. Copyright ©ERS 2016.

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 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)

Yields of 2-deoxy-D-gluconic, D-gluconic and other sugar acids in gamma-irradiated aqueous solutions of D-glucose. [Gamma rays

Energy Technology Data Exchange (ETDEWEB)

Esterbauer, H; Schubert, J; Sanders, E B; Sweeley, C C [Pittsburgh Univ., Pa. (USA); Michigan State Univ., East Lansing (USA). Dept. of Biochemistry)

1977-03-01

The yields of 2-deoxy-D-gluconic, D-gluconic and other sugar acids from /sup 60/Co-gamma irradiated (dose-rate = 4 Krads/min) D-glucose solutions are reported. The acids produced upon radiolysis were separated from glucose and neutral products by anion exchange, assayed by gas chromatography of the trimethylsilyl derivatives, and definitive identification made by mass spectrometry. In He degassed, irradiated 0.055 M glucose G(2-deoxy-D-gluconic acid) = 0.62 and G(D-gluconic acid) = 0.20. The approximate G values for the other identified acids are: glyceric acid 0.03, 2-deoxy-tetronic acid 0.04, tetronic acid 0.03, 4-deoxypentonic acid 0.02, deoxyketogluconic acid 0.17. In N/sub 2/O saturated glucose solutions D-gluconic acid yields increased by a factor of approximately 1.9 while that of 2-deoxy-D-gluconic acid increased by a factor of only approximately 1.1.

Antiangiogenic activity of 2-deoxy-D-glucose.

Directory of Open Access Journals (Sweden)

Jaime R Merchan

2010-10-01

Full Text Available During tumor angiogenesis, endothelial cells (ECs are engaged in a number of energy consuming biological processes, such as proliferation, migration, and capillary formation. Since glucose uptake and metabolism are increased to meet this energy need, the effects of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG on in vitro and in vivo angiogenesis were investigated.In cell culture, 2-DG inhibited EC growth, induced cytotoxicity, blocked migration, and inhibited actively forming but not established endothelial capillaries. Surprisingly, 2-DG was a better inhibitor of these EC properties than two more efficacious glycolytic inhibitors, 2-fluorodeoxy-D-glucose and oxamate. As an alternative to a glycolytic inhibitory mechanism, we considered 2-DG's ability to interfere with endothelial N-linked glycosylation. 2-DG's effects were reversed by mannose, an N-linked glycosylation precursor, and at relevant concentrations 2-DG also inhibited synthesis of the lipid linked oligosaccharide (LLO N-glycosylation donor in a mannose-reversible manner. Inhibition of LLO synthesis activated the unfolded protein response (UPR, which resulted in induction of GADD153/CHOP and EC apoptosis (TUNEL assay. Thus, 2-DG's effects on ECs appeared primarily due to inhibition of LLOs synthesis, not glycolysis. 2-DG was then evaluated in two mouse models, inhibiting angiogenesis in both the matrigel plug assay and the LH(BETAT(AG transgenic retinoblastoma model.In conclusion, 2-DG inhibits endothelial cell angiogenesis in vitro and in vivo, at concentrations below those affecting tumor cells directly, most likely by interfering with N-linked glycosylation rather than glycolysis. Our data underscore the importance of glucose metabolism on neovascularization, and demonstrate a novel approach for anti-angiogenic strategies.

2-deoxy-2-(18F)fluoro-D-glucose positron emission tomography/computed tomography imaging in paediatric oncology

Institute of Scientific and Technical Information of China (English)

John; Freebody; Eva; A; Wegner; Monica; A; Rossleigh

2014-01-01

Positron emission tomography(PET) is a minimally in-vasive technique which has been well validated for the diagnosis, staging, monitoring of response to therapy, and disease surveillance of adult oncology patients. Tra-ditionally the value of PET and PET/computed tomogra-phy(CT) hybrid imaging has been less clearly defined for paediatric oncology. However recent evidence has emerged regarding the diagnostic utility of these mo-dalities, and they are becoming increasingly important tools in the evaluation and monitoring of children with known or suspected malignant disease. Important indi-cations for 2-deoxy-2-(18F)fluoro-D-glucose(FDG) PET in paediatric oncology include lymphoma, brain tumours, sarcoma, neuroblastoma, Langerhans cell histiocytosis, urogenital tumours and neurofibromatosis type Ⅰ. This article aims to review current evidence for the use of FDG PET and PET/CT in these indications. Attention will also be given to technical and logistical issues, the description of common imaging pitfalls, and dosimetric concerns as they relate to paediatric oncology.

Synthesis of 2'-deoxy-2'-[{sup 18}F]-fluoro-5-iodo-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FIAU) and micro-PET imaging of suicide gene expression in tumor-bearing nude mice

Energy Technology Data Exchange (ETDEWEB)

Alauddin, M.M.; Shahinian, A.; Park, R.; Tohme, M.; Fissekis, J.D.; Conti, P.S. [Univ. of Southern California, Los Angeles, CA (United States). PET Imaging Science Center

2004-07-01

Herpes simplex virus type-1 thymidine kinase (HSV1-tk) is being used as a suicide gene for gene therapy of cancer. An in vivo method to assess the HSV1-tk enzyme activity after gene transfer is desirable to monitor gene expression as an indicator of gene delivery. Imaging of the HSV1-tk reporter gene along with various reporter probes is of current interest. We originally developed [{sup 18}F]-FHPG and [{sup 18}F]-FHBG for PET imaging of HSV1-tk gene expression and demonstrated that [{sup 18}F]-FHBG is more useful than [{sup 18}F]-FHPG for this purpose. [{sup 124}I]-FIAU has been shown to be a potential PET imaging agent for HSV1-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. We also demonstrated that radiolabeled FMAU can be used as a marker for HSV-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. Earlier we reported a synthesis for 2'-deoxy-2'-[{sup 18}F]fluoro-5-methyl-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FMAU) and some other 5-substituted nucleosides. We have synthesized now [{sup 18}F]-FIAU, used the tracer for micro-PET imaging of suicide gene expression in tumor-bearing nude mice, and compared the results with earlier studies using [{sup 14}C]-FMAU. (orig.)

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)

Synthesis of 2'-deoxy-2'-[{sup 18}F]-fluoro-5-ethyl-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FEAU) and micro-PET imaging of HSV-tk gene expression in tumor-bearing nude mice

Energy Technology Data Exchange (ETDEWEB)

Alauddin, M.M.; Shahinian, A.; Park, R.; Tohme, M.; Fissekis, J.D.; Conti, P.S. [Univ. of Southern California, Los Angeles, CA (United States). PET Imaging Science Center

2004-07-01

Herpes simplex virus type-1 thymidine kinase (HSV1-tk) is being used as a suicide gene for gene therapy of cancer. An in vivo method to assess the HSV1-tk enzyme activity after gene transfer is desirable to monitor gene expression as an indicator of gene delivery. Imaging of the HSV1-tk reporter gene along with various reporter probes is of current interest. We originally developed [{sup 18}F]-FHPG and [{sup 18}F]-FHBG for PET imaging of HSV1-tk gene expression and demonstrated that [{sup 18}F]-FHBG is more useful than [{sup 18}F]-FHPG for this purpose. [{sup 124}I]-FIAU has been shown to be a potential PET imaging agent for HSV1-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. We also demonstrated that radiolabeled FMAU can be used as a marker for HSV-tk gene expression, and is superior to [{sup 18}F]-FHPG and [{sup 18}F]-FHBG. Earlier we reported a synthesis for 2'-deoxy-2'-[{sup 18}F]fluoro-5-methyl-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]-FMAU) and some other 5-substituted nucleosides. We have synthesized now [{sup 18}F]-FEAU, used the tracer for micro-PET imaging of suicide gene expression in tumor-bearing nude mice, and compared the results with earlier studies using [{sup 14}C]-FMAU. (orig.)

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

Neuromyelitis optica spectrum disorder: 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography findings--case report.

Science.gov (United States)

Oyama, Hirofumi; Miwa, Shigeru; Noda, Tomoyuki; Sobajima, Atsuhiro; Kito, Akira; Maki, Hideki; Hattori, Kenichi; Wada, Kentaro

2012-01-01

A 51-year-old female with a history of rheumatoid arthritis rapidly developed anterior neck pain and paresis in the left upper and lower extremities and right lower extremity, sensory disturbance in the left upper and lower extremities, and bladder and rectal disorder. Adduction of the left eye and abduction of the right eye were also disturbed. Spinal magnetic resonance imaging demonstrated severe edema in the C1-T5 levels, which then deteriorated rapidly over 3 days, and lesions enhanced with gadolinium in the C1-C3 and C5-T3 levels. 2-Deoxy-2-[18F]fluoro-D-glucose positron emission tomography study demonstrated the inflammatory sites as segmental enhanced accumulation in the C1-C3, C5-C6, and T1 levels. The serum anti-aquaporin 4 antibody level was positive and she was diagnosed with neuromyelitis optica spectrum disorder. Marked improvement in the neurological conditions, concomitant with reduced spinal cord edema, was obtained by steroid pulse therapy.

2-deoxy-D-glucose but not 2-mercaptoacetate increases Fos-like immunoreactivity in adrenal medulla and sympathetic preganglionic neurons

NARCIS (Netherlands)

Ritter, S; Scheurink, A; Singer, LK

1995-01-01

2-Deoxy-D-glucose (2DG) and 2-mercaptoacetate (MA) are drugs that competetively inhibit metabolism of glucose and fatty acids, respectively, Both 2DG and MA stimulate food intake, In addition, 2DG-induced glucoprivation is a known stimulus for adrenomedullary secretion, However, very little is known

2-¹⁸fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) for postchemotherapy seminoma residual lesions

DEFF Research Database (Denmark)

Bachner, M; Loriot, Y; Gross-Goupil, M

2012-01-01

2-¹⁸fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) has been recommended in international guidelines in the evaluation of postchemotherapy seminoma residuals. Our trial was designed to validate these recommendations in a larger group of patients.......2-¹⁸fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) has been recommended in international guidelines in the evaluation of postchemotherapy seminoma residuals. Our trial was designed to validate these recommendations in a larger group of patients....

Early Treatment Response Monitoring Using 2-Deoxy-2-[18F]fluoro-D-glucose Positron Emission Tomography Imaging during Fractionated Radiotherapy of Head Neck Cancer Xenografts

Directory of Open Access Journals (Sweden)

Jiayi Huang

2014-01-01

Full Text Available Background. To determine the optimal timing and analytic method of 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (PET imaging during fractionated radiotherapy (RT to predict tumor control. Methods. Ten head neck squamous cell carcinoma xenografts derived from the UT-14-SCC cell line were irradiated with 50 Gy at 2 Gy per day over 5 weeks. Dynamic PET scans were acquired over 70 minutes at baseline (week 0 and weekly for seven weeks. PET data were analyzed using standard uptake value (SUV, retention index (RI, sensitivity factor (SF, and kinetic index (Ki. Results. Four xenografts had local failure (LF and 6 had local control. Eighty scans from week 0 to week 7 were analyzed. RI and SF after 10 Gy appeared to be the optimal predictors for LF. In contrast, SUV and Ki during RT were not significant predictors for LF. Conclusion. RI and SF of PET obtained after the first week of fractionated RT were the optimal methods and timing to predict tumor control.

Production of PET radiopharmaceutical 18F-FDG using synthesizer automatic module

International Nuclear Information System (INIS)

Purwoko; Chairuman; Adang Hardi Gunawan; Yayan Tahyan; Eny Lestari; Sri Aguswarini Lestiyowati; Karyadi; Sri Bagiawati

2010-01-01

Radiopharmaceutical 2-( 18 F)Fluoro-2-Deoxy-D-Glucose or 18 F(FDG) is an important PET (Positron Emission Tomography) radiopharmaceutical for tumour imaging. In the PET technique glucose metabolism in tumour tissues can be determined quantitatively and used for diagnosis staging and monitoring of treatment tumour or cancer disease in medical oncology. The production of 2-( 18 F)Fluoro-2-Deoxy-D-Glucose 18 F-FDG using compact automated system module TRACERlab MX has been carried out. The modular setup of the apparatus permits reliable for routine synthesis of radiopharmaceuticals 18 F-FDG based on kriptofix mediated nucleophilic fluorination to mannose triflate precursor. Radiochemical yield of 18 F-FDG was 53.895 % (decay time uncorrected) in 40 minutes. The product showed that the colorless and clear solution at pH:6, sterile and pirogen free, kriptofix impurities was low and radiochemical purity was 99.595%. (author)

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:

New and convenient synthesis of 2-deoxy-D-ribose from 2,4-O-ethylidene-D-erythrose

Energy Technology Data Exchange (ETDEWEB)

Hauske, J.R.; Rapoport, H.

1979-01-01

A new synthesis is described of 2-deoxy-D-erythro-pentose (2-deoxy-D-ribose,2-deoxy-D-arabinose (1)), starting from D-glucose. The synthesis proceeds through direct olefination of 2,4-O-ethylidene-D-erythrose (2) by addition of the stabilized ylides generated from dimethylphosphorylmethyl phenyl sulfide (4) and the corresponding sulfoxide 5. These afford the key intermediates, thio-enol ether 7 and ..cap alpha..,..beta..-unsaturated sulfoxide 8, which when subjected to mercuric ion assisted hydrolysis gave high yields of 2-deoxy-D-ribose (1). This facile chain extension of 2 required its existance as a monomer, and conditions effective for obtaining the monomer have been developed. Detailed /sup 1/H and /sup 13/C NMR studies of these compounds are presented.

Synthesis and Antiviral Activity of 3-Aminoindole Nucleosides of 2-Acetamido-2-deoxy-D-glucose

Energy Technology Data Exchange (ETDEWEB)

Abdelrahman, Adel A. H.; Elessawy, Farag A.; Barakat, Yousif A. [Menoufia Univ., Shebin El-Koam (Egypt); Ellatif, Mona M. Abd [The British Univ. in Egypt, Cairo (Egypt)

2012-10-15

A new method for the construction of 3-aminoindole nucleosides of 2-acetamido-2-deoxy-D-glucose based is presented. Nitration and acetylation of the indole nucleosides by acetic anhydride-nitric acid mixture followed by reduction using silver catalyst (SNSM) impregnated on silica gel, afforded the corresponding amino indole nucleosides. The nucleosides were tested for antiviral activity against hepatitis B virus (HBV) to show different degrees of antiviral activities or inhibitory actions.

Synthesis and quality control of 2-Fluoro-2-Deoxy-D-Glucose radiopharmaceuticals at Center of 30 MeV Cyclotron

International Nuclear Information System (INIS)

Vu Thanh Quang

2011-01-01

Positron Pharmaceuticals of 2-Fluoro-2-Deoxy-D-Glucose ( 18 F-FDG) is being produced routinely on Centre of 30 MeV cyclotron. Daily productions including the main stages are: Target of oxygen-18 rich water is irradiated by accelerated proton beam to create fluorine-18; Synthesis of 18 F-FDG use precursor manotriflate and quality control of the final product of 18 F-FDG is carried out as requirements of British Pharmacopoeia. Accounting until 11 Nov., 2010 the centre was in operation for 1 year. With capacity production of 3.5-4 Ci of 18 F-FDG/day, the centre has supplied 18 F-FDG for 150 patients imagined PET in the military central hospital and delivered 2035 mCi of 18 F-FDG for cancer centres of Bach Mai and Viet Duc hospitals. (author)

Factors influencing [F-18]2-fluoro-2-deoxy-D-glucose (F-18 FDG) uptake in melanoma cells. The role of proliferation rate, viability, glucose transporter expression and hexokinase activity

International Nuclear Information System (INIS)

Yamada, Kiyoshi; Brink, I.; Bisse, E.; Epting, T.; Engelhardt, R.

2005-01-01

Using human (SK-MEL 23, SK-MEL 24 and G361) and murine (B16) melanoma cell lines, the coregulatory potential of the uptake of the positron emission tomography (PET) tracer, [Fluorine-18]2-fluoro-2-deoxy-D-glucose (F-18 FDG) has been investigated in relationship to tumor characteristics. Comparative studies among the four melanoma cell lines demonstrated that the lowest FDG uptake in SK-MEL 24 corresponded strongly to the data for DT (population doubling time) and MTT (tetrazolium salt) cell viability as well as hexokinase (HK) activity, but was not related to the glucose transporter 1 (GLUT 1) expression level. Furthermore, the FDG uptake in each melanoma cell line measured by cell cycle kinetics was significantly positively correlated to both the proliferation index (PI=S/G 2 M phase fractions) and the cell viability, though with one exception relating to the proliferation index (PI) of the lowest FDG uptake cell line, SK-MEL 24. No positive correlation was found between the expression of GLUT 1 and FDG uptake in any individual cell line. However, the HK activities in SK-MEL 23 and 24 showed considerable positive relationships with FDG uptake. Our present study suggests that both the proliferation rate and the cell viability of melanoma cells may be key factors for FDG uptake and that HK activity, rather than GLUT 1 expression, seems to be a major factor. (author)

Radiation and chemical stability of 2-deoxy-2-[18F]fluoro-D-glucose radiopharmaceutical. Author-review of thesis

International Nuclear Information System (INIS)

Buriova, M.

2004-07-01

A qualitative and quantitative analytical technique of low-molecular components of chemical and radiation-chemical decomposition of 2-deoxy-2-[ 18 F]fluoro-D-glucose, 2-[ 18 F]FDG radiopharmaceutical was developed for its extended quality control by HPLC with mass-spectrometric electro-spray ionisation detector (ESI MS). The analysis constituted from the liquid chromatography on silica gel NH 2 bonded column combined with mass-spectrometric, UV-VIS, refraction index and radiometric detectors. A modern LC/MS system (Agilent 1100) was demonstrated to be suitable not only for identification of unknown analytes, but also for complex analysis of solutes except [ 18 F]F - . This was advantageous for the 2-[ 18 F]FDG autoradiolysis assessment about which no data were published. For comparative purposes, were used a classic thin layer chromatography (TLC) on silica gel with mobile phase acetonitril: water at 95:5 v/v, and HPTLC on NH 2 modified silica gel like the LC column. Mobile phase was identical as by LC/MS method (acetonitril: 4 mM aqueous solution of ammonium formate 80:20 v/v). Retention times of reference samples: fluorodeoxyglucose, glucose, mannose, arabinose, deoxyglucose, gluconic and glucuronic acids at HPLC were established. Optimal performance of the ESI MS detector was discovered in negative ions mode or single ion monitoring (SIM) regime. The most intensive signal was observed for all analyte molecules association with formate anion HCOO - and also for negative ions of deprotonised molecules. All acids appeared in the form of their lactones. FDG and Glc exhibited tendency for formation of a mixed associate charged by HCOO - anion. On the amine bond silica gel HPTLC column, FDG is poorly separated from fluoride, which even in presence of Kryptofix 2.2.2 remains on the start like on the silica gel layer. At LC-MS Kryptofix provides a very well measurable signals of associates with NH 4+ a H + ions in positive mode of ESI MS. Concentration of ( 19 F

Cerebral glucose metabolism in long-term survivors of childhood primary brain tumors treated with surgery and radiotherapy

DEFF Research Database (Denmark)

Andersen, Preben B.; Krabbe, Katja; Leffers, Anne M.

2003-01-01

a median recurrence free survival of 16 years by MRI and Positron Emission Tomography using the glucose analog 2-18F-fluoro-2-deoxy-D-glucose (18FDG). Three patients were not analyzed further due to diffuse cerebral atrophy, which might be related to previous hydrocephalus. Twenty-one patients were...

Distribution of adoptively transferred porcine T-lymphoblasts tracked by 18F-2-fluoro-2-deoxy-D-glucose and position emission tomography

International Nuclear Information System (INIS)

Eriksson, Olof; Sadeghi, Arian; Carlsson, Bjoern; Eich, Torsten; Lundgren, Torbjoern; Nilsson, Bo; Toetterman, Thomas; Korsgren, Olle; Sundin, Anders

2011-01-01

Introduction: Autologous or allogeneic transfer of tumor-infiltrating T-lymphocytes is a promising treatment for metastatic cancers, but a major concern is the difficulty in evaluating cell trafficking and distribution in adoptive cell therapy. This study presents a method of tracking transfusion of T-lymphoblasts in a porcine model by 18 F-2-fluoro-2-deoxy-D-glucose ([ 18 F]FDG) and positron emission tomography. Methods: T-lymphoblasts were labeled with the positron-emitting tracer [ 18 F]FDG through incubation. The T-lymphoblasts were administered into the bloodstream, and the distribution was followed by positron emission tomography for 120 min. The cells were administered either intravenously into the internal jugular vein (n=5) or intraarterially into the ascending aorta (n=1). Two of the pigs given intravenous administration were pretreated with low-molecular-weight dextran sulphate. Results: The cellular kinetics and distribution were readily quantifiable for up to 120 min. High (78.6% of the administered cells) heterogeneous pulmonary uptake was found after completed intravenous transfusion. The pulmonary uptake was decreased either by preincubating and coadministrating the T-lymphoblasts with low-molecular-weight dextran sulphate or by administrating them intraarterially. Conclusions: The present work shows the feasibility of quantitatively monitoring and evaluating cell trafficking and distribution following administration of [ 18 F]FDG-labeled T-lymphoblasts. The protocol can potentially be transferred to the clinical setting with few modifications.

Change in hexose distribution volume and fractional utilization of [18F]-2-deoxy-2-fluoro-D-glucose in brain during acute hypoglycemia in humans

International Nuclear Information System (INIS)

Shapiro, E.T.; Cooper, M.; Chen, C.T.; Given, B.D.; Polonsky, K.S.

1990-01-01

We used positron emission tomography (PET) to study the effects of mild hypoglycemia on cerebral glucose uptake and metabolism. Nine healthy men were studied under basal saline-infusion conditions, and during euglycemic and hypoglycemic clamp studies. Insulin was infused at the same rate (1 mU.kg-1.min-1) in both clamp studies. In euglycemic clamp studies, glucose was infused at a rate sufficient to maintain the basal plasma glucose concentration, whereas in hypoglycemic clamp studies, the glucose infusion rate was reduced to maintain the plasma glucose at 3.1 mM. Each study lasted 3 h and included a 30-min baseline period and a subsequent 150-min period in which insulin or glucose was administered. Blood samples for measurement of insulin, glucose, cortisol, growth hormone, and glucagon were obtained at 20- to 30-min intervals. A bolus injection of 5-10 mCi [18F]-2-deoxy-2-fluoro-D-glucose (2-DFG) was administered 120 min after initiation of the study, and plasma radioactivity and dynamic PET scans were obtained at frequent intervals for the remaining 40-60 min of the study. Cerebral regions of interest were defined, and concentrations of radioactivity were calculated and used in the three-compartment model of 2-DFG distribution described by Sokoloff. Glucose levels were similar during saline-infusion (4.9 +/- 0.1 mM) and euglycemic clamp (4.8 +/- 0.1 mM) studies, whereas the desired degree of mild hypoglycemia was achieved during the hypoglycemic clamp study (3.1 +/- 0.1 mM, P less than 0.05). The insulin level during saline infusion was 41 +/- 7 pM

2-18F-fluoro-2-deoxyglucose positron emission tomography in delirium.

Science.gov (United States)

Haggstrom, Lucy R; Nelson, Julia A; Wegner, Eva A; Caplan, Gideon A

2017-11-01

Delirium is a common, serious, yet poorly understood syndrome. Growing evidence suggests cerebral metabolism is fundamentally disturbed; however, it has not been investigated using 2- 18 F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) in delirium. This prospective study thus explored FDG PET patterns of cerebral glucose metabolism in older inpatients with delirium. A particular emphasis was on the posterior cingulate cortex (PCC), a key region for attention, which is a central feature of delirium. Delirium scans were compared with post-delirium scans using visual analysis and semi-quantitative analysis with NeuroQ; 13 participants (8 female, median 84 y) were scanned during delirium, and 6 scanned again after resolution. On visual analysis, cortical hypometabolism was evident in all participants during delirium (13/13), and improved with delirium resolution (6/6). Using NeuroQ, glucose metabolism was higher post-delirium in the whole brain and bilateral PCC compared to during delirium ( p delirium duration. This research found widespread, reversible cortical hypometabolism during delirium and PCC hypometabolism was associated with inattention during delirium.

Herpes simplex virus thymidine kinase imaging in mice with (1-(2'-deoxy-2'-[{sup 18}F]fluoro-1-{beta}-D-arabinofuranosyl)-5-iodouracil) and metabolite (1-(2'-deoxy-2'-[{sup 18}F]fluoro-1-{beta}-D-arabinofuranosyl)-5-uracil)

Energy Technology Data Exchange (ETDEWEB)

Nimmagadda, Sridhar; Lawhorn-Crews, Jawana M.; Shields, Anthony F. [Wayne State University, Karmanos Cancer Institute, Detroit, MI (United States); Wayne State University, Department of Medicine, Detroit, MI (United States); Mangner, Thomas J. [Wayne State University, Karmanos Cancer Institute, Detroit, MI (United States); Wayne State University, Department of Radiology, Detroit, MI (United States); Haberkorn, Uwe [University of Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany)

2009-12-15

FIAU, (1-(2{sup '}-deoxy-2{sup '}-fluoro-1-{beta}-D-arabinofuranosyl)-5-iodouracil) has been used as a substrate for herpes simplex virus thymidine kinases (HSV-TK and HSV-tk, for protein and gene expression, respectively) and other bacterial and viral thymidine kinases for noninvasive imaging applications. Previous studies have reported the formation of a de-iodinated metabolite of {sup 18}F-FIAU. This study reports the dynamic tumor uptake, biodistribution, and metabolite contribution to the activity of {sup 18}F-FIAU seen in HSV-tk gene expressing tumors and compares the distribution properties with its de-iodinated metabolite {sup 18}F-FAU. CD-1 nu/nu mice with subcutaneous MH3924A and MH3924A-stb-tk+ xenografts on opposite flanks were used for the biodistribution and imaging studies. Mice were injected IV with either {sup 18}F-FIAU or {sup 18}F-FAU. Mice underwent dynamic imaging with each tracer for 65 min followed by additional static imaging up to 150 min post-injection for some animals. Animals were sacrificed at 60 or 150 min post-injection. Samples of blood and tissue were collected for biodistribution and metabolite analysis. Regions of interest were drawn over the images obtained from both tumors to calculate the time-activity curves. Biodistribution and imaging studies showed the highest uptake of {sup 18}F-FIAU in the MH3924A-stb-tk+ tumors. Dynamic imaging studies revealed a continuous accumulation of {sup 18}F-FIAU in HSV-TK expressing tumors over 60 min. The mean biodistribution values (SUV {+-} SE) for MH3924A-stb-tk+ were 2.07 {+-} 0.40 and 6.15 {+-} 1.58 and that of MH3924A tumors were 0.19 {+-} 0.07 and 0.47 {+-} 0.06 at 60 and 150 min, respectively. In {sup 18}F-FIAU injected mice, at 60 min nearly 63% of blood activity was present as its metabolite {sup 18}F-FAU. Imaging and biodistribution studies with {sup 18}F-FAU demonstrated no specific accumulation in MH3924A-stb-tk+ tumors and SUVs for both the tumors were similar to those

Synthesis of 2-acetamido-6-O-(5-acetamido-3,5-dideoxy-β-D-glycero-D-galacto-2-nonulo-pyranosylonic acid)-2-deoxy-D-glucose [2-acetamido-6-O-(N-acetyl-β-D-neuraminyl)-2-deoxy-D-glucose

NARCIS (Netherlands)

Vliegenthart, J.F.G.; Vleugel, D.J.M. van der; Zwikker, J.W.; Boeckel, S.A.A. van; Boom, J.H. van

1982-01-01

Silver triflate-promoted condensation of methyl 5-acetamido-4,7,8,9-tetra-O-acetyl-2-chloro-2,3,5-trideoxy-β-D-glycero-D-galacto -2-nonulopyranosonate (9) with benzyl-2-acetamido-2-deoxy-3,4-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-α-D-glucopyranoside, followed by removal of the

Conversion of 2-deoxy-D-ribose into 2-amino-5-(2-deoxy-beta-D-ribofuranosyl)pyridine, 2'-deoxypseudouridine, and other C-(2'-deoxyribonucleosides).

Science.gov (United States)

Reese, Colin B; Wu, Qinpei

2003-09-21

The synthesis of 2-amino-5-(2-deoxy-beta-D-ribofuranosyl)pyridine 2a, 2-amino-5-(2-deoxy-alpha-D-ribofuranosyl)-pyridine 23, 2-amino-5-(2-deoxy-beta-D-ribofuranosyl)-3-methylpyridine 2b, 2-amino-5-(2-deoxy-alpha-D-ribofuranosyl)-3-methylpyridine 29 and 5-(2-deoxy-beta-D-ribofuranosyl)-2,4-dioxopyrimidine [2'-deoxypseudouridine] 30a is described. These C-nucleosides are prepared either from 2-deoxy-3,5-O-(1,1,3,3-tetraisopropyldisiloxan-1,3-diyl)-D-ribofuranose 15 or from 2-deoxy-3,5-O-(1,1,3,3-tetraisopropyldisiloxan-1,3-diyl)-D-ribono-1,4-lactone 16, which are themselves prepared from 2-deoxy-D-ribose 13. The sugar derivatives are first allowed to react with the appropriate 5-lithio-pyridine or 5-lithio-pyrimidine derivatives, which are prepared from 5-bromo-2-(dibenzylamino)pyridine 12a, 5-bromo-2-[bis(4-methoxybenzyl)amino]pyridine 12b, 5-bromo-2-dibenzylamino-3-methylpyridine 25 and 5-bromo-2,4-bis(4-methoxybenzyloxy)pyrimidine 33. The products from the reactions between the lithio-derivatives and the lactol 15 are cyclized under Mitsunobu conditions; the products from the reactions between the lithio-derivatives and the lactone 16 are first reduced with L-Selectride before cyclization, also under Mitsunobu conditions. In all cases, the beta-anomers of the protected C-nucleosides are the predominant products. Finally, the separation of the alpha- and beta-anomers and the removal of all of the protecting groups are described.

Digitonin abolishes free 2-deoxy-D-glucose accumulation in isolated rat adipocytes

International Nuclear Information System (INIS)

Thompson, K.; Kleinzeller, A.

1986-01-01

The hypothesis that accumulation against sizable chemical gradients of free (non-phosphorylated) 2-deoxy-D-glucose (2dGlc) in isolated rat adipocytes results from an intracellular compartmentation of free hexose was investigated. Cells exposed to 20 μg/ml digitonin for 10' demonstrated an increased plasma membrane permeability indexed by increased L-glucose entry rates and cellular (presumably cytosolic) protein and K + loss. Functional integrity of intracellular organelles was indicated by the ability of the cells to support ATP-driven 45 Ca 2+ -uptake. Equilibrium 3-O-methylglucose (3-O-MG, a non-accumulated hexose) levels were unaffected. These data suggest a specific permeabilizing action of digitonin at the plasma membrane having no effect on intracellular organelles or passively distributed solutes. Upon addition of digitonin, free 2dGlc fell from 66.5 +/- 8.9 to 7.4 +/- 2.3 pmol/10 5 cells, a value not significantly different from 3-O-MG levels. The gradient of 2dGlc-phosphate was also abolished, as was the increased steady-state free 2dGlc levels induced by insulin. The data argue against a compartmentation model as either the mechanism of adipocyte sugar accumulation or the basis of the steady-state free 2dGlc increase seen with insulin and suggest that an intact plasma membrane is essential to the process

Factors influencing [F-18]2-fluoro-2-deoxy-D-glucose (F-18 FDG) accumulation in melanoma cells. Is FDG a substrate of multidrug resistance (MDR)?

International Nuclear Information System (INIS)

Yamada, Kiyoshi; Brink, I.; Engelhardt, R.

2005-01-01

In order to specify the influence of multidrug-resistance (MDR) on the accumulation of the PET tracer, F-18 FDG ([Fluorine-18]2-fluoro-2-deoxy-D-glucose, in melanoma cells, both the MDR function and expression of two human melanoma cell lines SK-MEL 23 and 24, were evaluated. The effects of MDR modulators on FDG accumulation and efflux were also investigated. A functional analysis using representative MDR fluorescent substrates and inhibitors clarified the following characteristics: SK-MEL 23 possesses a highly active function of multidrug resistance-associated protein (MRP), but not P-gp. SK-MEL 24 possesses weak functions of both MRP and P-gp. Western blot analysis using monoclonal antibodies for MDR expression demonstrated an exceedingly high MRP expression of SK-MEL 23 and only slight P-gp and MRP expression of SK-MEL 24, corresponding to the functional data. The efflux inhibition assay using F-18 FDG revealed a considerable retention of FDG in SK-MEL 23 in the presence of the MRP inhibitor probenecid. It was also found that the P-gp inhibitor verapamil depressed the FDG efflux of SK-MEL 24. Our present in vitro study suggests that FDG may be a substrate of MDR in some melanoma cells and further MDR may be one of the important factors affecting FDG-PET melanoma imaging. (author)

Crossed cerebellar diaschisis. A positron emission tomography study with L-[methyl-11C]methionine and 2-deoxy-2-[18F]fluoro-D-glucose

International Nuclear Information System (INIS)

Kajimoto, Katsufumi; Oku, Naohiko; Kimura, Yasuyuki

2007-01-01

Crossed cerebellar diaschisis (CCD) is defined as a depression of blood flow and oxidative metabolism of glucose in the cerebellum contralateral to a supratentorial brain lesion, as detected with positron emission tomography (PET) and single photon emission computed tomography. We examined whether L-[methyl- 11 C]methionine (MET) uptake is affected in CCD. In 12 patients with a unilateral supratentorial brain tumor, we evaluated the uptake of 2-deoxy-2-[ 18 F]fluoro-D-glucose (FDG) and MET in the cerebellar hemispheres by means of PET. Asymmetry index (AI) was defined as a difference in the average count between the ipsilateral and contralateral cerebellar hemispheres divided by the average count in both cerebellar hemispheres. Patients with AI of FDG PET more than 0.1 and those with AI equal to 0.1 or less than 0.1 were classified as CCD-positive and CCD-negative, respectively. Six patients were CCD-positive and others were CCD-negative in the FDG PET study. Between CCD-positive and CCD-negative patients, mean AI of MET was not significantly different (0.017±0.023 and 0.014±0.039, respectively). Different from glucose metabolism, cerebellar MET uptake was not affected in CCD. The present study may indicate that cerebellar MET uptake is independent of suppression of cerebellar neuronal activity. (author)

Changes in 2-fluoro-2-deoxy-D-glucose incorporation, hexokinase activity and lactate production by breast cancer cells responding to treatment with the anti-HER-2 antibody trastuzumab

Energy Technology Data Exchange (ETDEWEB)

Cheyne, Richard W. [School of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD (United Kingdom); Trembleau, Laurent; McLaughlin, Abbie [School of Natural and Computing Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD (United Kingdom); Smith, Tim A.D., E-mail: t.smith@abdn.ac.u [School of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD (United Kingdom)

2011-04-15

Introduction: Changes in 2-[{sup 18}F]-fluoro-2-deoxy-D-glucose (FDG) incorporation by tumors, detected using positron emission tomography, during response to chemotherapy are utilized clinically in patient management. Here, the effect of treatment with growth-inhibitory doses of the anti-human epidermal growth factor receptor-2 antibody trastuzumab (Herceptin) on the incorporation of FDG by breast tumor cells was measured along with hexokinase (HK) and glucose transport to determine the potential of FDG-positron emission tomography in predicting response to these biological anti-cancer therapies and their modulatory effects on the steps involved in FDG incorporation. Methods: The sensitivity to trastuzumab of three breast tumor cell lines, SKBr3, MDA-MB-453 and MDA-MB-468, expressing human epidermal growth factor receptor-2 at high, medium and low levels, respectively, was determined using MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay over a 6-day period, and a clonogenic assay was carried out after 7- and 10-day exposures. FDG incorporation by cells treated with growth-inhibitory doses of trastuzumab was carried out after 4 h and 2, 4 and 6 days of treatment. Glucose transport (rate of uptake of the non-metabolizable analogue [{sup 3}H]O-methyl-D-glucose), HK activity and lactate production were measured on cells treated with inhibitory doses of trastuzumab for 6 days. Results: The IC{sub 50} doses for SKBr3 and MDA-MB-453 and the IC{sub 20} dose for MDA-MB-468 after 6 days of treatment with trastuzumab were 0.25, 1 and 170 {mu}g/ml, respectively. FDG incorporation by SKBr3 and MDA-MB-453 cells was found to be decreased using IC{sub 50} doses of trastuzumab for 6 days. At the IC{sub 50} doses, FDG incorporation was also decreased at 4 days and, in the case of MDA-MB-453, even after 4 h of treatment. Decreased FDG incorporation corresponded with decreased HK activity in these cells. Lactate production, previously suggested to be a

Immunohistochemical overexpression of hypoxia-induced factor 1α associated with slow reduction in {sup 18}fluoro-2-deoxy-D-glucose uptake for chemoradiotherapy in patients with pharyngeal cancer

Energy Technology Data Exchange (ETDEWEB)

Chen, Shang-Wen [China Medical University Hospital, Department of Radiation Oncology, Taichung (China); China Medical University, School of Medicine, Taichung (China); Taipei Medical University, School of Medicine, Taipei (China); Lin, Ying-Chun [China Medical University Hospital, Department of Radiation Oncology, Taichung (China); China Medical University and Academia Sinica, The Ph.D. Program for Cancer Biology and Drug Discovery, Taichung (China); Chen, Rui-Yun [China Medical University Hospital, Department of Pathology, Taichung (China); Hsieh, Te-Chun; Yen, Kuo-Yang [China Medical University Hospital, Department of Nuclear Medicine and PET Center, Taichung (China); China Medical University, Department of Biomedical Imaging and Radiological Science, Taichung (China); Liang, Ji-An [China Medical University Hospital, Department of Radiation Oncology, Taichung (China); China Medical University, Graduate Institute of Clinical Medical Science, School of Medicine, College of Medicine, Taichung (China); Yang, Shih-Neng [China Medical University Hospital, Department of Radiation Oncology, Taichung (China); China Medical University, Department of Biomedical Imaging and Radiological Science, Taichung (China); Wang, Yao-Ching [China Medical University Hospital, Department of Radiation Oncology, Taichung (China); Chen, Ya-Huey [China Medical University, Graduate Institute of Cancer Biology, Taichung (China); China Medical University Hospital, Center for Molecular Medicine, Taichung (China); Chow, Nan-Haw [National Cheng Kung University, Department of Pathology, Tainan (China); Kao, Chia-Hung [China Medical University Hospital, Department of Nuclear Medicine and PET Center, Taichung (China); China Medical University, Graduate Institute of Clinical Medical Science, School of Medicine, College of Medicine, Taichung (China)

2016-12-15

This study examined genomic factors associated with a reduction in {sup 18}fluoro-2-deoxy-D-glucose (FDG) uptake during positron emission tomography-computed tomography (PET-CT) for definitive chemoradiotherapy (CRT) in patients with pharyngeal cancer. The pretreatment and interim PET-CT images of 25 patients with advanced pharyngeal cancers receiving definitive CRT were prospectively evaluated. The maximum standardized uptake value (SUV{sub max}) of the interim PET-CT and the reduction ratio of the SUV{sub max} (SRR) between the two images were measured. Genomic data from pretreatment incisional biopsy specimens (SLC2A1, CAIX, VEGF, HIF1A, BCL2, Claudin-4, YAP1, MET, MKI67, and EGFR) were analyzed using tissue microarrays. Differences in FDG uptake and SRRs between tumors with low and high gene expression were examined using the Mann-Whitney test. Cox regression analysis was performed to examine the effects of variables on local control. The SRR of the primary tumors (SRR-P) was 0.59 ± 0.31, whereas the SRR of metastatic lymph nodes (SRR-N) was 0.54 ± 0.32. Overexpression of HIF1A was associated with a high iSUV{sub max} of the primary tumor (P < 0.001) and neck lymph node (P = 0.04) and a low SRR-P (P = 0.02). Multivariate analysis revealed that patients who had tumors with low SRR-P or high HIF1A expression levels showed inferior local control. In patients with pharyngeal cancer requiring CRT, HIF1A overexpression was positively associated with high interim SUV{sub max} or a slow reduction in FDG uptake. Prospective trials are needed to determine whether the local control rate can be stratified using the HIF1A level as a biomarker and SRR-P. (orig.)

Cellular localization of 2-[3H]deoxy-D-glucose from paraffin-embedded brains

International Nuclear Information System (INIS)

Durham, D.; Woolsey, T.A.; Kruger, L.

1981-01-01

Results of experiments in which regional neuronal activity is revealed by a 2-[ 3 H]deoxy-D-glucose ( 3 H-2-DG)-paraffin section-emulsion autoradiography method are described. The trigeminal pathway of freely behaving mice was activated differentially by selective patterns of whisker removal. One hour after injection of concentrated 3 H-2-DG, the animals were perfused systemically with a periodate/lysine/paraformaldehyde mixture the brains were embedded in paraffin, and serial sections were taken and coated with emulsion for autoradiography. Diffusion of the isotope out of the tissue was assessed visually and by liquid scintillation counting. While substantial loss of 3 H isotope into the embedding fluids (about 95%) was found, the scintillation counts and the autoradiograms showed good fixation of the isotope in situ, no evidence of isotope movement into the emulsion, and no gradients of diffusion in the sectioned material. Patterns of regional labeling were similar to those reported from brains prepared by conventional 2-[ 14 C]deoxy-D-glucose ( 14 C-2-DG) autoradiography; Trigeminal structures associated with the intact (stimulated) whiskers were labeled relatively heavily, indicating that label uptake is specific with respect to neuronal activity. In the cortex, the patterns of label corresponded directly and precisely to those barrels known to receive inputs from the intact whiskers. Distribution of silver grains in the cortex and in the brainstem was correlated directly with neuronal profiles. Clearly, this approach offers considerable technical advantages, in particular, the ease with which the histological material is prepared. The resolution of the autoradiograms and the quality of the histology are excellent

Distribution of adoptively transferred porcine T-lymphoblasts tracked by {sup 18}F-2-fluoro-2-deoxy-D-glucose and position emission tomography

Energy Technology Data Exchange (ETDEWEB)

Eriksson, Olof, E-mail: olof.eriksson@radiol.uu.se [Division of Radiology, Department of Oncology, Radiology, Oncology and Radiation Science, Uppsala University, Uppsala 751 87 (Sweden); Uppsala Imanet AB, GE Healthcare, Uppsala 751 85 (Sweden); Sadeghi, Arian; Carlsson, Bjoern; Eich, Torsten [Division of Immunology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala 751 87 (Sweden); Lundgren, Torbjoern [Division of Transplantation Surgery, CLINTEC, Karolinska Institute, Stockholm 171 77 (Sweden); Nilsson, Bo; Toetterman, Thomas; Korsgren, Olle [Division of Immunology, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala 751 87 (Sweden); Sundin, Anders [Division of Radiology, Department of Oncology, Radiology, Oncology and Radiation Science, Uppsala University, Uppsala 751 87 (Sweden); Department of Radiology, Karolinska University Hospital and Molecular Medicine and Surgery, Karolinska Institute, Stockholm 171 77 (Sweden)

2011-08-15

Introduction: Autologous or allogeneic transfer of tumor-infiltrating T-lymphocytes is a promising treatment for metastatic cancers, but a major concern is the difficulty in evaluating cell trafficking and distribution in adoptive cell therapy. This study presents a method of tracking transfusion of T-lymphoblasts in a porcine model by {sup 18}F-2-fluoro-2-deoxy-D-glucose ([{sup 18}F]FDG) and positron emission tomography. Methods: T-lymphoblasts were labeled with the positron-emitting tracer [{sup 18}F]FDG through incubation. The T-lymphoblasts were administered into the bloodstream, and the distribution was followed by positron emission tomography for 120 min. The cells were administered either intravenously into the internal jugular vein (n=5) or intraarterially into the ascending aorta (n=1). Two of the pigs given intravenous administration were pretreated with low-molecular-weight dextran sulphate. Results: The cellular kinetics and distribution were readily quantifiable for up to 120 min. High (78.6% of the administered cells) heterogeneous pulmonary uptake was found after completed intravenous transfusion. The pulmonary uptake was decreased either by preincubating and coadministrating the T-lymphoblasts with low-molecular-weight dextran sulphate or by administrating them intraarterially. Conclusions: The present work shows the feasibility of quantitatively monitoring and evaluating cell trafficking and distribution following administration of [{sup 18}F]FDG-labeled T-lymphoblasts. The protocol can potentially be transferred to the clinical setting with few modifications.

Time course of radiolabeled 2-deoxy-D-glucose 6-phosphate turnover in cerebral cortex of goats

International Nuclear Information System (INIS)

Pelligrino, D.A.; Miletich, D.J.; Albrecht, R.F.

1987-01-01

The vivo dephosphorylation rate of 2-deoxy-D-glucose 6-phosphate (DGP) in the cerebral cortex of goats injected intravenously with radiolabeled 2-deoxy-D-glucose (DG) was investigated. Serial rapidly frozen samples of parietal cortical gray tissue were obtained at regular intervals over time periods from 45 min to 3 h in awake goats or in paralyzed and artificially ventilated goats maintained under 70% N 2 O or pentobarbital sodium anesthesia. The samples were analyzed for glucose content and separate DG and DGP activities. The rate parameters for phosphorylation (k/sup */ 4 ) and dephosphorylation (k/sup */ 4 ) were estimated in each animal. The glucose phosphorylation rate (PR) was calculated over the intervals 3-5 (or 6), 3-10, 3-20, 3-30, and 3-45 min, assuming k/sup */ 4 = O. As the evaluation period was extended beyond 10 min, the calculated PR became increasingly less when compared with that calculated over the 3- to 5- (or 6) min interval (PR/sub i/). Furthermore, as metabolic activity decreased, the magnitude of the error increased such that at 45 min pentobarbital-anesthetize goats underestimated the PR/sub i/ by 46.5% compared with only 23.1 in N 2 O-anesthetized goats. This was also reflected in the >twofold higher k/sup */ 4 /k/sup */ 3 ratio in the pentobarbital vs. N 2 O-anesthetized group. It is concluded that when using the DG method in the goat, DGP dephosphorylation cannot be ignored when employing >10-min evaluation periods

The frequency and spectrum of thymus 2-[fluorine-18] fluoro-2-deoxy-D-glucose uptake patterns in hyperthyroidism patients.

Science.gov (United States)

Chen, Yen-Kung; Yeh, Chia-Lu; Chen, Yen-Ling; Wang, Su-Chen; Cheng, Ru-Hwa; Kao, Pan-Fu

2011-10-01

Thymic hyperplasia is associated with hyperthyroidism. Increased thymus 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG) uptake in hyperthyroidism patients has been reported. The aim of this study was to analyze the FDG positron emission tomography (PET) thymus uptake spectrum in patients with active hyperthyroidism with correlation with serum hormones. The prospective study included FDG PET scans from 65 hyperthyroidism patients and 30 subjects with euthyroid status as control group. The intensity of FDG uptake in thyroid and thymus regions was graded subjectively on a five-point scale and semi-quantitatively by measuring standard uptake value (SUV). Correlation coefficient between thymus SUV and serum thyroxine, triiodothyronine, thyrotropin, thyroid peroxidase antibodies (TPO Ab), thyrotropin receptor autoantibody (TR Ab), and thymulin were analyzed. Among 65 hyperthyroidism patients, 30 (46.2%) and 39 (60%) patients showed thyroid and thymus FDG uptake, respectively. The frequency of thymus uptake FDG was high in patients younger than age 40 (28/31, 90.3%). The patterns of the thymic FDG uptake include inverted V or triangular, separated triangular, united nontriangular, unilateral right or left extension, and focal midline. Focal midline FDG uptake was the most common pattern (15/39, 38.5%). None of the control group showed thymus FDG uptake. The correlation coefficient between the FDG uptake SUV levels in thymus and serum hormones, thyrotropin, TPO Ab, TR Ab, and thymulin levels were all low (P > .05). In FDG PET scan, thymus activity was common in hyperthyroidism patients; this should not be misdiagnosed as a malignancy in patients exhibiting weight loss. Copyright © 2011 AUR. Published by Elsevier Inc. All rights reserved.

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

The significance of alteration 2-[fluorine-18]fluoro-2-deoxy-(D)-glucose uptake in the liver and skeletal muscles of patients with hyperthyroidism.

Science.gov (United States)

Chen, Yen-Kung; Chen, Yen-Ling; Tsui, Chih-Cheng; Wang, Su-Chen; Cheng, Ru-Hwa

2013-10-01

Hyperthyroidism leads to an enhanced demand for glucose. The hypothesis of the study is that 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) can demonstrate the alteration of systemic glucose metabolism in hyperthyroidism patients by measuring the FDG standard uptake value (SUV) in liver and skeletal muscle. Forty-eight active hyperthyroidism patients and 30 control participants were recruited for the study. The intensity of FDG uptake in the liver and thigh muscles was graded subjectively, comprising three groups: group I, higher FDG uptake in the liver; group II, equal FDG uptake in the liver and muscles; and group III, higher FDG uptake in the muscles. Ten subjects with FDG PET scans at hyperthyroid and euthyroid status were analyzed. Serum levels of thyroxine (T4) and triiodothyronine (T3) correlated to the SUVs of the liver and muscles. Forty-one patients (41/48, 85.4%) showed symmetrically increased FDG uptake in the muscles (22 in group I, 9 in group II, and 17 in group III). Group I patients were significantly older than group II (P = .02) and group III (P = .001) patients. The correlation coefficient between the serum T3, T4, and SUV levels in the muscles was significant (r = 0.47-0.77, P hyperthyroid and euthyroid states. In the 30 control subjects, there was normal physiological FDG uptake in the liver and muscles. In PET scans showing a pattern of decreased liver and increased skeletal muscle FDG uptake in hyperthyroidism patients, this change of FDG distribution is correspondence to the severity of hyperthyroidism status. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Local cerebral metabolic rate of glucose (lCMRGlc) in treated and untreated patients with Parkinson's disease

International Nuclear Information System (INIS)

Rougemont, D.; Baron, J.C.; Collard, P.; Bustany, P.; Comar, D.; Agid, Y.

1983-06-01

Local cerebral metabolic rate of glucose (lCMRGlc) was measured twice, using positron emission tomography and 18 F-Fluoro-2-deoxy-D-glucose ( 18 FDG), in 4 patients with Parkinson disease, first unmedicated and then treated with L-DOPA. Despite a dramatic clinical improvement, no significant changes in lCMRGlc could be detected. Moreover, no reproducible differences of lCMRGlc were found between patients with Parkinson disease and with normal brain

Associations between liver 18F fluoro-2-deoxy-D-glucose accumulation and various clinical parameters in a Japanese population. Influence of the metabolic syndrome

International Nuclear Information System (INIS)

Kamimura, Kiyohisa; Nagamachi, Shigeki; Wakamatsu, Hideyuki

2010-01-01

Liver demonstrates a heterogeneous 18 F fluoro-2-deoxy-D-glucose ( 18 F-FDG) uptake pattern and sometimes shows an abnormally increased uptake even when there is no malignant tissue. The aim of this study was to evaluate the relationships of liver 18 F-FDG uptake as related to physical factors, fatty liver, blood glucose (BG), and other biochemical data. 18 F-FDG positron emission tomography (PET) imaging was performed in 101 consecutive subjects for cancer screening. Multiple stepwise regression analysis was used to define the best predictors of the liver standardized uptake value (SUV) among height, weight, waist circumference, body mass index (BMI), systolic and diastolic blood pressure, BG and other biochemical data, id est (i.e.), aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, total cholesterol, high-density lipoprotein cholesterol, triglycerides, total protein, total bilirubin, and alkaline phosphatase. Furthermore, we evaluated the association between liver 18 F-FDG uptake and the metabolic syndrome. The independent factors for increased liver 18 F-FDG uptake (mean SUV >=2) were BMI (P 18 F-FDG uptake. In addition, the liver 18 F-FDG uptake of metabolic syndrome subjects was significantly higher than that of a non-metabolic syndrome subjects. BMI was the strongest determinant of liver 18 F-FDG uptake, and the liver 18 F-FDG uptake of metabolic syndrome subjects was significantly higher than that of non-metabolic syndrome subjects. This result suggests that a subject with a high liver 18 F-FDG uptake should be screened for the metabolic syndrome. (author)

Metabolic mapping of functional activity in human subjects with the [18F]fluorodeoxyglucose technique

International Nuclear Information System (INIS)

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

1981-01-01

The 2-[ 18 F]fluoro-2-deoxy-D-glucose technique was used to measure regional cerebral glucose utilization by human subjects during functional activation. Normal male volunteers subjected to one or more sensory stimuli exhibited focal increases in glucose metabolism in response to the stimulus. These results demonstrate that the technique is capable of providing functional maps in vivo related to both body region and submodality of sensory information in the human brain

18F-FDG PET/CT in detection of gynecomastia in patients with hepatocellular carcinoma.

Science.gov (United States)

Wang, Hsin-Yi; Jeng, Long-Bin; Lin, Ming-Chia; Chao, Chih-Hao; Lin, Wan-Yu; Kao, Chia-Hung

2013-01-01

We retrospectively investigate the prevalence of gynecomastia as false-positive 2-[18F]fluoro-2-deoxy-d-glucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) imaging in patients with hepatocellular carcinoma (HCC). Among the 127 male HCC patients who underwent 18F-FDG PET/CT scan, the 18FDG uptakes at the bilateral breasts in 9 patients with gynecomastia were recorded as standard uptake value (SUVmax) and the visual interpretation in both early and delayed images. The mean early SUVmax was 1.58/1.57 (right/left breast) in nine gynecomastia patients. The three patients with early visual score of 3 had higher early SUVmaxs. Gynecomastia is a possible cause of false-positive uptake on 18F-FDG PET/CT images. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of 2-deoxy-D-glucose administration on cytokine production in BDF1 mice

Science.gov (United States)

Dreau, D.; Morton, D. S.; Foster, M.; Fowler, N.; Sonnenfeld, G.

2000-01-01

Physical exercise and diet changes have been shown to affect immune parameters, and similar effects are also induced by the administration of a nonmetabolizable glucose analog, 2-deoxy-D-glucose (2-DG). The present study was designed to characterize the effects of glucoprivation induced by 2-DG administration on concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 in the blood and interferon-gamma (IFN-gamma), IL-2, and IL-4 in vitro production by partially purified T splenocytes in BDF1 mice. Mice (n = 8 per group) were injected intraperitoneally one or three times with 0, 500, 750, or 1000 mg/kg of 2-DG, and blood and spleens were collected 2 h after the last injection. Partially purified T splenocytes were cultured 24 h in the presence of concanavalin A (ConA). A significant increase in the corticosterone levels with the amount of 2-DG injected was observed after one or three injections (pproduction in the culture supernatants and an increase in IL-1 receptor expression on the cell surface (p<0.05).

Improving the yield of 2-[18F]fluoro-2-deoxyglucose using a microwave cavity.

Science.gov (United States)

Taylor, M D; Roberts, A D; Nickles, R J

1996-07-01

We have investigated the use of a microwave cavity (Labwell AB, Sweden) to improve the radiochemical yield of 2-[18F]fluoro-2-deoxyglucose (2-[18F]FDG). After characterizing the heating properties of the cavity, three steps of the Hamacher 2-[18F]FDG synthesis which require heating--azeotropic distillation of the target water, nucleophilic substitution, and hydrolysis of the product--were investigated separately. The average radiochemical yield of 2-[18F]FDG for the microwave synthesis, using the phase transfer reagent tetrabutylammonium bicarbonate, was 62 +/- 4% (72 +/- 5%, decay corrected, synthesis time = 31 min).

Improving the yield of 2-[18F]fluoro-2-deoxyglucose using a microwave cavity

International Nuclear Information System (INIS)

Taylor, M.D.; Roberts, A.D.; Nickles, R.J.

1996-01-01

We have investigated the use of a microwave cavity (Labwell AB, Sweden) to improve the radiochemical yield of 2-[ 18 F]fluoro-2-deoxyglucose (2-[ 18 F]FDG). After characterizing the heating properties of the cavity, three steps of the Hamacher 2-[ 18 F]FDG synthesis which require heating--azeotropic distillation of the target water, nucleophilic substitution, and hydrolysis of the product--were investigated separately. The average radiochemical yield of 2-[ 18 F]FDG for the microwave synthesis, using the phase transfer reagent tetrabutylammonium bicarbonate, was 62 ± 4% (72 ± 5%, decay corrected, synthesis time = 31 min)

Local cerebral metabolic rate of glucose (lCMRGlc) in treated and untreated patients with Parkinson's disease

Energy Technology Data Exchange (ETDEWEB)

Rougemont, D; Baron, J C; Collard, P; Bustany, P; Comar, D; Agid, Y

1983-06-01

Local cerebral metabolic rate of glucose (lCMRGlc) was measured twice, using positron emission tomography and /sup 18/F-Fluoro-2-deoxy-D-glucose (/sup 18/FDG), in 4 patients with Parkinson disease, first unmedicated and then treated with L-DOPA. Despite a dramatic clinical improvement, no significant changes in lCMRGlc could be detected. Moreover, no reproducible differences of lCMRGlc were found between patients with Parkinson disease and with normal brain.

2-[18 F]fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography (PET) findings of chronic expanding intrapericardial hematoma: a potential interpretive pitfall that mimics a malignant tumor

Science.gov (United States)

2013-01-01

A 77-year-old man who had undergone mitral valve replacement 5 years previously presented with an intrapericardial mass. Computed tomography and magnetic resonance imaging showed that the mass lesion contained hematoma components. Positron-emission tomography (PET) with 2-[18 F] fluoro-2-deoxy-d-glucose (FDG) revealed uptake in the peripheral rim of the mass. These findings suggested the presence of hematoma associated with a malignant lesion. Surgical resection was performed, and the histological diagnosis was chronic expanding intrapericardial hematoma without neoplastic changes. Chronic expanding intrapericardial hematoma is a rare disease but should be considered when an expanding mass is found in a patient after cardiac surgery. The FDG-PET findings of chronic expanding hematomas, including FDG uptake in the peripheral rim of the mass as a result of inflammation, should be recognized as a potential interpretive pitfall that mimics a malignant tumor. PMID:23324446

Modulation of cellular radiation responses by 2-deoxy-D-glucose and other glycolytic inhibitors: Implications for cancer therapy

OpenAIRE

Kalia Vijay; Prabhakara S; Narayanan Vidya

2009-01-01

Background: 2-Deoxy-D-glucose (2-DG), a glycolytic inhibitor, was observed earlier to increase DNA, chromosomal, and cellular damage in tumor cells, by inhibiting energy-dependent repair processes. Lonidamine (LND) selectively inhibits glycolysis in cancer cells. It damages the condensed mitochondria in these cells, impairing thereby the activity of hexokinase (predominantly attached to the outer mitochondrial membranes). It inhibits repair of radiation-induced potentially lethal cellular da...

Measurement of regional cerebral metabolic rate for glucose in the human subject with (F-18)-2-deoxy-2-fluoro-d-glucose and emission computed tomography: validation of the method

International Nuclear Information System (INIS)

Phelps, M.E.; Huang, S.C.; Hoffman, E.J.; Selin, C.; Kuhl, D.E.

1977-01-01

Tracer techniques and models of in vitro quantitative autoradiography and tissue counting for the measure of regional metabolic rates (rMR) are combined with emission computed tomography (ECT). This approach, Physiologic Tomography (PT), provides atraumatic and analytical measurements of rMR. PT is exemplified with the regional measurement of the cerebral metabolic rate for glucose (CMRGlu) in man with ( 18 F)-2-deoxy-2-fluoro-D-glucose (FDG) and positron ECT. Our model incorporates a k 4 * mediated hydrolysis of FDG-6-PO 4 to FDG which then competes with phosphorylation (k 3 *) of FDG back to FDG-6-PO 4 and reverse transport (k 2 *) back to blood. Although small, k 4 * is found to be significant. The ECAT positron tomograph was used to measure the rate constants (k 1 *→k 4 *), lumped constant (LC), stability, and reproducibility of the model in man. Since these parameters have not been measured for FDG in any species, comparisons are made to values for DG in rat and monkey. Compartmental concentrations of FDG and FDG-6-PO 4 were determined and show that cerebral FDG-6-PO 4 steadily accumulates for about 100 mins, plateaus and then slowly decreases due to hydrolysis. Cerebral blood FDG concentration was determined to be a minor contribution to tissue activity after 10 min. Regional CMRGlu measurements are reproducible to +- 5.5% over 5 hrs. PT allows the in vivo study ofregional biochemistry and physiology in normal and pathophysiologic states in man with a unique and fundamental capability

2-deoxy-d-glucose (2-DG) inhibits radiation induced carcinogenesis (skin tumors) in mice

International Nuclear Information System (INIS)

Singh, Saurabh; Bhuria, Vikas; Pandey, Sanjay; Saluja, Daman; Dwarakanath, B.S.

2014-01-01

One of the late effects of radiation exposure i.e. carcinogenesis is exemplified by atomic bomb survivors, radiotherapy patients and occupational workers. Enhanced glucose metabolism (Warburg's effect) is a fundamental metabolic change in transformed cells which drives tumorigenesis. It is suggested that Dietary Energy Restriction (DER) that targets glucose metabolism may afford protection against radiation-induced carcinogenesis. However, DER is practically difficult to sustain in humans. Therefore, we have hypothesized that the glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), a potential energy restriction mimetic agent (ERMA) may impair the process of tumorigenesis as an alternative to DER. In the present studies we investigated the effects of dietary 2-DG on radiation induced papillomas in mice. Swiss albino mice (male) were irradiated with a fractionated dose schedule (1.5 Gy ionizing radiation/week for four weeks) focally on the shaved back followed by the application of tumor promoting agent (TPA) once weekly till the termination of the study. Mice were administered 2-DG (0.2% and 0.4% w/v) containing water starting a week after last irradiation. A significant reduction in the tumor incidence, tumor burden, besides increase in the latency period was observed in the 2-DG fed mice. The average tumor incidence (papillomas formation) was reduced to 25% and 37% in 0.2% and 0.4% 2-DG group respectively from 47% in the control group with a significant delay in the onset. Under these conditions, 2-DG considerably enhanced the level of reduced glutathione (GSH) with a concomitant decrease in the lipid peroxidation. 2-DG fed tumor bearing mice showed decrease in splenic CD4 + to CD8 + T-cell ratio and prevented the tumor induced augmentation of T-regulatory cells (CD4 + CD25 + ) which correlated with an increase in CD8 + (CTLs) cells. Dietary 2-DG also reduced the tumor associated and radiation induced angiogenesis. These observations suggest that dietary 2-DG

Can 3'-Deoxy-3'-((18)F) Fluorothymidine Out Perform 2-Deoxy-2-((18)F) Fluoro-D-Glucose Positron Emission Tomography/Computed Tomography in the Diagnosis of Cervical Lymphadenopathy in Patients With Oral/Head and Neck Cancer?

Science.gov (United States)

Schaefferkoetter, Joshua D; Carlson, Eric R; Heidel, Robert E

2015-07-01

The present study investigated the performance of cellular metabolism imaging with 2-deoxy-2-((18)F) fluoro-D-glucose (FDG) versus cellular proliferation imaging with 3'-deoxy-3'-((18)F) fluorothymidine (FLT) in the detection of cervical lymph node metastases in oral/head and neck cancer. We conducted a prospective cohort study to assess a head-to-head performance of FLT imaging and clinical FDG imaging for characterizing cervical lymph node metastases in patients with squamous cell carcinoma (SCC) of the oral/head and neck region. The primary predictor variable of the study was the presence of FDG or FLT avidity within the cervical lymph nodes. The primary outcome variable was the histologic presence of metastatic SCC in the cervical lymph nodes. The performance was reported in terms of the sensitivity, specificity, accuracy, and positive and negative predictive values. The overall accuracy for discriminating positive from negative lymph nodes was evaluated as a function of the positron emission tomography (PET) standardized uptake value (SUV). Receiver operating characteristic (ROC) analyses were performed for both tracers. Eleven patients undergoing surgical resection of SCC of the oral/head and neck region underwent preoperative FDG and FLT PET-computed tomography (CT) scans on separate days. The interpretation of the FDG PET-CT imaging resulted in sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 43.2, 99.5, 94.4, 88.9, and 94.7%, respectively. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for FLT PET-CT imaging was 75.7, 99.2, 97.1, 90.3, and 97.7%, respectively. The areas under the curve for the ROC curves were 0.9 and 0.84 for FDG and FLT, respectively. Poor correlation was observed between the SUV for FDG and FLT within the lymph nodes and tumors. FLT showed better overall performance for detecting lymphadenopathy on qualitative assessment within the total

Glucosamine metabolism of herpes simplex virus infected cells. Inhibition of glycosylation by tunicamycin and 2-deoxy-D-glucose

International Nuclear Information System (INIS)

Olofsson, S.; Lycke, E.

1980-01-01

The formation of glucosamine-containing cell surface glycoproteins of herpes simplex virus (HSV) infected BMK cells was studied. Tunicamycin (TM) and 2-deoxy-D-glucose (DG) were used as inhibitors. With both inhibitors the multiplication of HSV was inhibited. DG markedly reduced cellular uptake of radioactively labelled glucosamine while TM interfered with the processing of glucosamine into TCA-insoluble material. Gel filtration chromatography on Sephadex G50 gel of cell surface material released by trypsin and further prepared by digestion with pronase indicated that TM and DG reduced the apparent high molecular weights of virus induced surface glycoproteins. In presence of DG the accumulation of a class of glucosamine-containing heterosaccharides (MW less than 3000) not present on DG-free HSV infected cells was observed. IN TM treated cells virtually all surface heterosaccharides with molecular weights exceeding 3000 and containing glucosamine disappeared. Moreover, a component compatible with a lipid-linked oligosaccharide present in DG treated cells was not observed in HSV infected TM treated cells. The results exemplifies some different steps in glucosamine metabolism of virus-induced cell surface glycoproteins differently affected by tunicamycin and 2-deoxy-D-glucose. (author)

Tumour and lymph node uptakes on dual-phased 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography correlate with prognostic parameters in breast cancer.

Science.gov (United States)

Chang, Chin-Chuan; Tu, Hung-Pin; Chen, Yu-Wen; Lin, Chia-Yang; Hou, Ming-Feng

2014-12-01

To examine correlations between the uptake of 2-deoxy-2-[18F]fluoro-D-glucose (FDG) by primary tumours and axillary lymph nodes, and clinical and biological tumour prognostic parameters, in patients with newly diagnosed breast cancer. Newly diagnosed breast cancer patients who had received a dual-phased FDG positron emission tomography/computed tomography scan for pretreatment staging were enrolled retrospectively. Maximal standardized uptake values at 1 h (SUV1), 2 h (SUV2), and retention indices (RI) of the tumours and ipsilateral axillary lymph nodes were measured. SUV and RI were compared with clinical and biological prognostic parameters. A total of 32 patients participated in the study. Tumour FDG uptake correlated with histological grade and tumour size. FDG uptake in axillary lymph nodes correlated positively with lymph node status, metastasis status and clinical stage. RI values for the tumour and lymph nodes were significantly positively correlated with human epidermal growth factor receptor-2 positivity. FDG uptake in tumours and lymph nodes showed correlations with some clinical and biological parameters, and may serve as a predictive marker of tumour biological behaviour in breast cancer. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Dielectric relaxation study of the dynamics of monosaccharides: D-ribose and 2-deoxy-D-ribose

Energy Technology Data Exchange (ETDEWEB)

Kaminski, K; Kaminska, E; Wlodarczyk, P; Paluch, M; Ziolo, J [Institute of Physics, Silesian University, ulica Uniwersytecka 4, 40-007 Katowice (Poland); Ngai, K L [Naval Research Laboratory, Washington, DC 20375-5320 (United States)

2008-08-20

The dielectric loss spectra of two closely related monosaccharides, D-ribose and 2-deoxy-D-ribose, measured at ambient and elevated pressures are presented. 2-deoxy-D-ribose and D-ribose are respectively the building blocks of the backbone chains in the nucleic acids DNA (deoxyribonucleic acid) and RNA (ribonucleic acid). Small differences in the structure between D-ribose and 2-deoxy-D-ribose result in changes of the glass transition temperature T{sub g}, as well as the dielectric strength and activation enthalpy of the secondary relaxations. However, the frequency dispersion of the structural {alpha}-relaxation for the same relaxation time remains practically the same. Two secondary relaxations are present in both sugars. The slower secondary relaxation shifts to lower frequencies with increasing applied pressure, but not the faster one. This pressure dependence indicates that the slower secondary relaxation is the important and 'universal' Johari-Goldstein {beta}-relaxation of both sugars according to one of the criteria set up to classify secondary relaxations. Additional confirmation of this conclusion comes from good agreement of the observed relaxation time of the slower secondary relaxation with the primitive relaxation time calculated from the coupling model. All the dynamic properties of D-ribose and 2-deoxy-D-ribose are similar to the other monosaccharides, glucose, fructose, galactose and sorbose, except for the much larger relaxation strength of the {alpha}-relaxation of the former compared to the latter. The difference may distinguish the chemical and biological functions of D-ribose and 2-deoxy-D-ribose from the other monosaccharides.

Evaluation of whole-body cancer screening using 18F-2-deoxy-2-fluoro-D-glucose positron emission tomography. A preliminary report

International Nuclear Information System (INIS)

Terauchi, Takashi; Murano, Takeshi; Daisaki, Hiromitsu; Kanou, Daisuke; Shoda, Hiroko; Kakinuma, Ryutaro; Hamashima, Chisato; Moriyama, Noriyuki; Kakizoe, Tadao

2008-01-01

18 F-2-deoxy-2-fluoro-d-glucose positron emission tomography (FDG-PET) is a promising screening modality targeting whole body. However, the validity of PET cancer screening remains to be assessed. Even the screening accuracy for whole-body screening using FDG-PET has not been evaluated. In this study, we investigated the screening accuracy of PET cancer screening. A total of 2911 asymptomatic participants (1629 men and 1282 women, mean age 59.79 years) underwent both FDG-PET and other thorough examinations for multiple organs (gastrofiberscopy, total colonofiberscopy or barium enema, low-dose thin section computed tomography and sputum cytology, abdominal ultrasonography, an assay of prostate-specific antigen, mammography, mammary ultrasonography, Pap smear for the uterine cervix, and magnetic resonance imaging for the endometrium and ovaries) between February 2004 and January 2005, and followed sufficiently. The detection rate, sensitivity, specificity, and positive predictive value of FDG-PET were calculated using cancer data obtained from all examinations along with a 1 year follow-up. From among 2911 participants FDG-PET found 28 cancers, 129 cancers were PET negative. PET-positive cancers comprised seven colorectal cancers, four lung cancers, four thyroid cancers, three breast cancers, two gastric cancers, two prostate cancers, two small intestinal sarcomas (gastrointestinal stromal tumors), one malignant lymphoma, one head and neck malignancy (nasopharyngeal carcinoid tumor), one thymoma, and one hepatocellular carcinoma. PET-negative cancers included 22 gastric cancers and 20 prostate cancers that were essentially difficult to detect using FDG-PET. The overall detection rate, sensitivity, specificity, and positive predictive value were estimated to be 0.96%, 17.83%, 95.15%, and 11.20%, respectively. FDG-PET can detect a variety of cancers at an early stage as part of a whole-body screening modality. The detection rate of PET cancer screening was higher than

Assessment of infarct size by positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose: a new absolute threshold technique

International Nuclear Information System (INIS)

Chareonthaitawee, P.; Iozzo, Patricia; Schaefers, K.; Stegger, L.; Baker, C.S.R.; Camici, Paolo G.; Rimoldi, Ornella; Turkheimer, F.; Banner, N.R.; Yacoub, Magdi; Bonser, Robert S.

2002-01-01

Along with hibernating myocardium, infarct size is a critical term in the progression of left ventricular remodelling and congestive heart failure. Both infarcted and hibernating myocardium determine changes in remote non-ischaemic tissue. This study was designed to test the accuracy of a new technique to quantify infarct size using positron emission tomography (PET) with [ 18 F]2-fluoro-2-deoxy-D-glucose (FDG). Studies were carried out in (a) nine pigs with acute myocardial infarction (two sham-operated), produced by a 90-min occlusion of the circumflex coronary artery followed by a 4-h reperfusion, and (b) humans (six patients with ischaemic cardiomyopathy awaiting cardiac transplantation and five normal volunteers). In both animals and patients, myocardial FDG uptake was measured by PET during hyperinsulinaemic-euglycaemic clamp. Infarct size was quantified by an absolute threshold of tracer uptake obtained from the parametric (voxel-by-voxel) image of the metabolic rate of FDG. PET infarct size estimates were compared with independent ex vivo planimetric measurements of the explanted swine and patient hearts (at transplantation) after staining with triphenyltetrazolium chloride. There was good agreement between the planimetric and PET infarct size estimates both in pigs (n=9; r=0.96, y=0.94x +0.64, SEE=0.10, P<0.0001) and in humans (n=11; r=0.94, y=0.72x +2.93, SEE=0.09, P<0.0001). This study demonstrates the feasibility and accuracy of this PET method in estimating infarct size both in a model of reperfused acute myocardial infarction and in chronic ischaemic cardiomyopathy, although larger studies are needed to confirm these findings. (orig.)

Differentiation between malignant and benign pathologic fractures with F-18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography

Energy Technology Data Exchange (ETDEWEB)

Shin, D.S.; Shon, O.J.; Byun, S.J. [Yeungnam University, Department of Orthopedic Surgery College of Medicine, Daegu (Korea); Choi, J.H. [Yeungnam University, Department of Surgical Pathology, College of Medicine, Daegu (Korea); Chun, K.A.; Cho, I.H. [Yeungnam University, Department of Nuclear Medicine, College of Medicine, Daegu (Korea)

2008-05-15

To evaluate the efficacy of F-18-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG PET/CT) in differentiating malignant from benign pathologic fractures. F-18 FDG PET/CT was performed on 34 patients with pathologic fractures between May 2004 and June 2007. Fractures were located in tubular bones (26), in the pelvis (six), in the spine (one) and in a rib (one). The FDG uptake pattern at the fracture site was described, whether FDG uptake occurred in the marrow or cortex and soft tissue. Maximum standardized uptake values (SUVmax, the largest value at the region of interest) were measured at the fracture site, including cortical bone, bone marrow and soft tissue. As a reference standard, biopsy was used for 12 patients and clinical follow-up for 22 patients. Sensitivity, specificity and diagnostic accuracy of PET/CT were calculated. There were 19 malignant and 15 benign fractures. In the malignant fractures, PET/CT demonstrated high (mean SUVmax 12.0, range 4.3 to 45.7) F-18 FDG uptake in bone marrow in most cases (17 of 19). In benign fractures, there was low FDG uptake (mean SUVmax 2.9, range 0.6 to 5.5) within cortical bone or adjacent soft tissue around the fracture, rarely in the marrow. There were significant differences in the pattern of intramedullary FDG uptake (P < 0.001) and in the mean SUVmax (P < 0.01) between malignant and benign fractures. The sensitivity, specificity and diagnostic accuracy of F-18 FDG PET/CT were 89.5%, 86.7% and 88.2%, respectively, with a cut-off SUVmax set at 4.7. The time interval between fracture and PET/CT did not significantly influence FDG uptake at the fracture site. F-18 FDG PET/CT reliably differentiated between malignant and benign fractures based on the SUVmax and based on medullary uptake, which was characteristic for malignant fractures. (orig.)

40 CFR 721.2076 - D-Glucuronic acid, polymer with 6-deoxy-L-mannose and D-glucose, acetate, calcium magnesium...

Science.gov (United States)

2010-07-01

...-deoxy-L-mannose and D-glucose, acetate, calcium magnesium potassium sodium salt. 721.2076 Section 721...-Glucuronic acid, polymer with 6-deoxy-L-mannose and D-glucose, acetate, calcium magnesium potassium sodium... identified as D-Glucuronic acid, polymer with 6-deoxy-L-mannose and D-glucose, acetate, calcium magnesium...

Tritiated 2-deoxy-D-glucose: a high-resolution marker for autoradiographic localization of brain metabolism

International Nuclear Information System (INIS)

Hammer, R.P. Jr.; Herkenham, M.

1984-01-01

The technique for autoradiographic localization of 2-deoxy-D-glucose (2DG) uptake has become a useful method for observing alterations of functional brain activity resulting from experimental manipulation. Autoradiographic resolution is improved using tritiated ([3H]) rather than carbon-14 ([14C)]2DG, due to the lower energy and shorter path of tritium emissions. In addition, lower 2DG uptake by white matter relative to gray matter is exaggerated in the [3H]2DG autoradiographs due to the greater absorption of tritium emissions by lipids. Using [3H]2DG, it is possible to observe differential metabolic labeling in various individual nuclei or portions of nuclei that is unresolvable using [14C]2DG in the awake, normal animal. Heterogeneous patterns of 2DG uptake seen only with [3H]2DG are found in the nucleus accumbens, the anterior portion of the basolateral nucleus of the amygdala, specific nuclei of the inferior olivary complex, various hypothalamic regions, and a region straddling the border of the medial and lateral habenular nuclei. The lamination of differential 2DG uptake in the hippocampus is better localized using [3H]2DG. Autoradiographic resolution of labeled 2DG is further improved when the brain is perfused prior to frozen sectioning, due perhaps to selective fixation and retention of intracellular labeled 2-deoxy-glycogen. A series of [3H]2DG autoradiographs are presented together with views of the Nissl-stained sections that produced the autoradiographs

18F-FDG PET/CT-based early treatment response evaluation of nanoparticle-assisted photothermal cancer therapy.

Science.gov (United States)

Norregaard, Kamilla; Jørgensen, Jesper T; Simón, Marina; Melander, Fredrik; Kristensen, Lotte K; Bendix, Pól M; Andresen, Thomas L; Oddershede, Lene B; Kjaer, Andreas

2017-01-01

Within the field of nanoparticle-assisted photothermal cancer therapy, focus has mostly been on developing novel heat-generating nanoparticles with the right optical and dimensional properties. Comparison and evaluation of their performance in tumor-bearing animals are commonly assessed by changes in tumor volume; however, this is usually a late-occurring event. This study implements 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography imaging to perform early evaluation of the treatment outcome of photothermal therapy. Silica-gold nanoshells (NS) are administered intravenously to nude mice bearing human neuroendocrine tumor xenografts and the tumors are irradiated by a near-infrared laser. The animals are positron emission tomography scanned with 2-deoxy-2-[F-18]fluoro-D-glucose one day before and one day after treatment. Using this setup, a significant decrease in tumor uptake of 2-deoxy-2-[F-18]fluoro-D-glucose is found already one day after therapy in the group receiving NS and laser treatment compared to control animals. At this time point no change in tumor volume can be detected. Moreover, the change in tumor uptake, is used to stratify the animals into responders and non-responders, where the responding group matched improved survival. Overall, these findings support the use of 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography imaging for preclinical and clinical evaluation and optimization of photothermal therapy.

Design, synthesis and evaluation of 2-deoxy-2-iodovinyl-branched carbohydrates as potential brain imaging agents

International Nuclear Information System (INIS)

Goodman, M.M.; Callahan, A.P.; Knapp, F.F. Jr.

1986-01-01

Radioiodinated carbohydrates such as 2-deoxy-2-iodo-D-glucose and 3-deoxy-3-iodo-D-glucose undergo facile chemical or in vivo deiodination which precludes their use as radiotracers of glucose metabolism in tissues. To overcome the problems resulting from in vivo deiodination, we explored the concept of stabilizing radioiodide on a model carbohydrate, (E)-C-3-iodovinyl-D-allose as an iodovinyl moiety. This agent did not exhibit brain specificity but showed low in vivo deiodination which demonstrated for the first time that radioiodide can be stabilized on a carbohydrate. The goal of this study was to develop a deoxy-branched carbohydrate with radioiodide stabilized as a vinyliodide with the objective of achieving high brain uptake. (author)

2-deoxy-2-(18F)fluoro-D-galactose: a new tracer for the evaluation of liver function by PET, 1

International Nuclear Information System (INIS)

Fukuda, Hiroshi; Yamaguchi, Keiichiro; Matsuzawa, Taiju

1987-01-01

We have developed a positron-labeled galactose analog, 2-deoxy-2-[ 18 F]fluoro-D-galactose ( 18 FDGal), and showed its potential for the evaluation of galactose metabolism in the liver by PET in animal studies. In this paper, we described about toxicity of FDGal and radiation dose to the organs from 18 FDGal. LD 50 of FDGal to ICR mice and rats were more than 800 mg/kg and radiation doses from 18 FDGal calculated using MIRD schema were 541, 446, 252 and 50 mrad/mCi, respectively, to the liver, bladder wall, kidney and total body. These were permissible values for clinical use of 18 FDGal. (author)

Detectability of colorectal neoplasia with fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography and computed tomography (FDG-PET/CT)

International Nuclear Information System (INIS)

Hirakawa, Tomoko; Okumura, Yoshihiro; Kato, Jun

2012-01-01

The purpose of this study was to analyze the detectability of colorectal neoplasia with fluorine-18-2-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT). Data for a total of 492 patients who had undergone both PET/CT and colonoscopy were analyzed. After the findings of PET/CT and colonoscopy were determined independently, the results were compared in each of the six colonic sites examined in all patients. The efficacy of PET/CT was determined using colonoscopic examination as the gold standard. In all, 270 colorectal lesions 5 mm or more in size, including 70 pathologically confirmed malignant lesions, were found in 172 patients by colonoscopy. The sensitivity and specificity of PET/CT for detecting any of the colorectal lesions were 36 and 98%, respectively. For detecting lesions 11 mm or larger, the sensitivity was increased to 85%, with the specificity remaining consistent (97%). Moreover, the sensitivity for tumors 21 mm or larger was 96% (48/50). Tumors with malignant or high-grade pathology were likely to be positive with PET/CT. A size of 10 mm or smaller [odds ratio (OR) 44.14, 95% confidence interval (95% CI) 11.44-221.67] and flat morphology (OR 7.78, 95% CI 1.79-36.25) were significant factors that were associated with false-negative cases on PET/CT. The sensitivity of PET/CT for detecting colorectal lesions is acceptable, showing size- and pathology-dependence, suggesting, for the most part, that clinically relevant lesions are detectable with PET/CT. However, when considering PET/CT for screening purposes caution must be exercised because there are cases of false-negative results. (author)

Immune Alterations in Male and Female Mice after 2-Deoxy-D-Glucose Administration

Science.gov (United States)

Dreau, Didier; Morton, Darla S.; Foster, Mareva; Swiggett, Jeanene P.; Sonnenfeld, Gerald

1995-01-01

Administration of 2-deoxy-D-glucose (2-DG), an analog of glucose which inhibits glycolysis by competitive antagonism for phosphohexose isomerase, results in acute periods of intracellular glucoprivation and hyperglycemia resulting in hyperphagia. In addition to these changes in the carbohydrate metabolism, injection of 2-DG results in alterations of both the endocrine and neurological systems as suggested by modifications in oxytocin and glucocorticoid levels and norepinephrine production. Moreover, alterations of the immune response, such as a decrease in the in vitro proliferation of splenocytes after mitogen-stimulation, were observed in mice injected with 2-DG. Sex, genotype and environment are among the factors that may modulate effects of catecholamines and hypothalamo-pituitary-adrenal axis on these immune changes. Sexual dimorphism in immune function resulting from the effects of sex hormones on immune effector cells has been shown in both animals and humans. These observations have important implications, especially with regard to higher incidence of many autoimmune diseases in females. Evidence exists that reproductive hormones influence the immune system and increase the risk of immunologically related disorders in both animals and humans. Indeed, immunological responses in stressful situations may also be confounded by fluctuations of sex hormones especially in females. Lymphocyte distribution, cytoldne production, and the ability of lymphocyte to proliferate in vitro were analyzed in male and female mice to determine if sex influenced 2-DG immunomodulation. In addition, the influence of hormones, especially sex hormones, on these changes were evaluated.

Design, synthesis and evaluation of 2-deoxy-2-iodovinyl-branched carbohydrates as potential brain imaging agents

International Nuclear Information System (INIS)

Goodman, M.M.; Callahan, A.P.; Knapp, F.F. Jr.

1986-01-01

Radioiodinated carbohydrates such as 2-deoxy-2-iodo-D-glucose and 3-deoxy-3-iodo-D-glucose undergo facile chemical or in vivo deiodination which precludes their use as radiotracers of glucose metabolism in tissues. To overcome the problems resulting from in vivo deiodination, we explored the concept of stabilizing radioiodide on a model carbohydrate, (E)-C-3-iodovinyl-D-allose (10) as an iodovinyl moiety. This agent did not exhibit brain specificity but showed low in vivo deiodination which demonstrated for the first time that radioiodide can be stabilized on a carbohydrate. The goal of this study was to develop a deoxy-branched carbohydrate with radioiodide stabilized as a vinyliodide with the objective of achieving high brain uptake. 10 refs., 1 fig., 1 tab

Design, synthesis and evaluation of 2-deoxy-2-iodovinyl-branched carbohydrates as potential brain imaging agents

Energy Technology Data Exchange (ETDEWEB)

Goodman, M.M.; Callahan, A.P.; Knapp, F.F. Jr.

1986-01-01

Radioiodinated carbohydrates such as 2-deoxy-2-iodo-D-glucose and 3-deoxy-3-iodo-D-glucose undergo facile chemical or in vivo deiodination which precludes their use as radiotracers of glucose metabolism in tissues. To overcome the problems resulting from in vivo deiodination, we explored the concept of stabilizing radioiodide on a model carbohydrate, (E)-C-3-iodovinyl-D-allose (10) as an iodovinyl moiety. This agent did not exhibit brain specificity but showed low in vivo deiodination which demonstrated for the first time that radioiodide can be stabilized on a carbohydrate. The goal of this study was to develop a deoxy-branched carbohydrate with radioiodide stabilized as a vinyliodide with the objective of achieving high brain uptake. 10 refs., 1 fig., 1 tab.

Inhibition of induced tumorigenesis by dietary 2-deoxy-D-Glucose in mice

International Nuclear Information System (INIS)

Singh, Saurabh; Pandey, Sanjay; Bhuria, Vikas; Bhatt, Anant Narayan; Taneja, Pankaj; Soni, Ravi; Dwarakanath, Bilikere S.; Oberoi, Raghav; Chawla, Aman Preet; Saluja, Daman

2014-01-01

Enhanced glycolysis facilitating proliferation and defence against death, besides energy production is a fundamental metabolic change exhibited by majority of the tumor types. Recent evidences support Warburg's proposition that this metabolic re-programming may also drive tumorigenesis induced by chemical carcinogens and radiation. Targeting this phenotype using the glycolytic inhibitor, 2-deoxy-D glucose (2-DG) has been shown to enhance the efficacy of radiation and chemotherapeutic drugs in experimental systems as well as clinics. 2-DG is also a potent Energy Restriction Mimetic Agent (ERMA) as an alternative to Dietary Energy Restriction (DER) for combating cancer. Since DER regimen is difficult to sustain in humans, we have hypothesized that 2-DG may impair the process of induced tumorigenesis, thereby offering an attractive chemopreventive strategy. Systematic studies have indeed shown that dietary 2-DG administration impairs the formation and growth of implanted tumor (Lewis Lung carcinoma; Ehrlich ascites carcinoma) as well as chemical (DMBA and TPA) and radiation-induced skin tumors in C57BL/6, Strain A and Swiss Albino mice respectively in the tumor implant study. Decrease in the fraction of animals bearing tumor and growth rate, besides increase in the latency period were evident. In the chemical and radiation induced tumor studies, a significant reduction in the percentage of tumor (papillomas) bearing animals (incidence), number of tumors per animal (tumor burden) and increased latency were observed. Although, mechanisms underlying cancer preventive/inhibitory potential of dietary 2-DG is not completely understood, our current findings suggests modifications of certain circulating factors (glucose and insulin), oxidative stress (LPO and GSH), immune status (CD4/CD8 and regulatory T-cells; T-regs), extracellular matrix (MMP-9) and angiogenesis (tumor associated and radiation-induced) as some of the contributing factors. Further studies are required

18F-FDG PET/CT-based early treatment response evaluation of nanoparticle-assisted photothermal cancer therapy.

Directory of Open Access Journals (Sweden)

Kamilla Norregaard

Full Text Available Within the field of nanoparticle-assisted photothermal cancer therapy, focus has mostly been on developing novel heat-generating nanoparticles with the right optical and dimensional properties. Comparison and evaluation of their performance in tumor-bearing animals are commonly assessed by changes in tumor volume; however, this is usually a late-occurring event. This study implements 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography imaging to perform early evaluation of the treatment outcome of photothermal therapy. Silica-gold nanoshells (NS are administered intravenously to nude mice bearing human neuroendocrine tumor xenografts and the tumors are irradiated by a near-infrared laser. The animals are positron emission tomography scanned with 2-deoxy-2-[F-18]fluoro-D-glucose one day before and one day after treatment. Using this setup, a significant decrease in tumor uptake of 2-deoxy-2-[F-18]fluoro-D-glucose is found already one day after therapy in the group receiving NS and laser treatment compared to control animals. At this time point no change in tumor volume can be detected. Moreover, the change in tumor uptake, is used to stratify the animals into responders and non-responders, where the responding group matched improved survival. Overall, these findings support the use of 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography imaging for preclinical and clinical evaluation and optimization of photothermal therapy.

Using positron emission tomography (PET) response criteria in solid tumours (PERCIST) 1.0 for evaluation of 2'-deoxy-2'-[18F] fluoro-D-glucose-PET/CT scans to predict survival early during treatment of locally advanced non-small cell lung cancer (NSCLC).

Science.gov (United States)

Fledelius, Joan; Khalil, Azza Ahmed; Hjorthaug, Karin; Frøkiaer, Jørgen

2016-04-01

The demand for early-response evaluation with 2'-deoxy-2'-[18F] fluoro-D-glucose (F-18-FDG) positron emission tomography combined with whole body CT (PET/CT) is rapidly growing. This study was initiated to evaluate the applicability of the PET response criteria in solid tumours (PERCIST 1.0) for response evaluation. We performed a retrospective study of 21 patients with locally advanced non-small cell lung cancer (NSCLC), who had undergone both a baseline and a follow-up F-18-FDG-PET/CT scan during their treatments. The scans were performed at our institution in the period September 2009 and March 2011 and were analysed visually and according to PERCIST 1.0 by one board-certified nuclear medicine physician. The response was compared with overall survival (OS) and progression-free survival (PFS). The variation in key parameters affecting the F-18-FDG uptake was assessed. A kappa of 0.94 corresponding to an almost perfect agreement was found for the comparison of the visual evaluation with PERCIST. Patients with partial metabolic response and stable metabolic disease (as evaluated by PERCIST 1.0) had statistically significant longer median time to progression: 8.4 months (confidence interval (CI) 5.1-11.8 months) as compared with 2.7 months (CI 0-5.6 months) in patients classified with progression. The variation in uptake time between baseline and follow-up scans was more than the recommended 15 min in 48% of patients. PERCIST 1.0 is readily implementable and highly comparable with visual evaluation of response using early F-18-FDG-PET/CT scanning for locally advanced NSCLC patients. In spite of variations in parameters affecting F-18-FDG uptake, evaluation of F-18-FDG-PET/CT during treatment with PERCIST 1.0 is shown to separate non-responders from responders, each with statistically significant differences in both OS and PFS. © 2015 The Royal Australian and New Zealand College of Radiologists.

Effects of 2-deoxy-D-glucose administration on cytokine production in BDF1 mice

Science.gov (United States)

Dreau, D.; Morton, D. S.; Foster, M.; Fowler, N.; Sonnenfeld, G.

2000-01-01

Physical exercise and diet changes have been shown to affect immune parameters, and similar effects are also induced by the administration of a nonmetabolizable glucose analog, 2-deoxy-D-glucose (2-DG). The present study was designed to characterize the effects of glucoprivation induced by 2-DG administration on concentrations of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6 in the blood and interferon-gamma (IFN-gamma), IL-2, and IL-4 in vitro production by partially purified T splenocytes in BDF1 mice. Mice (n = 8 per group) were injected intraperitoneally one or three times with 0, 500, 750, or 1000 mg/kg of 2-DG, and blood and spleens were collected 2 h after the last injection. Partially purified T splenocytes were cultured 24 h in the presence of concanavalin A (ConA). A significant increase in the corticosterone levels with the amount of 2-DG injected was observed after one or three injections (palpha, IL-1beta, and IL-6 concentrations in the blood of mice after one or three injections of 2-DG (p<0.05). A significant decrease in in vitro proliferation of partially purified splenocytes in the presence of ConA was associated with a decrease in IFN-gamma production in the culture supernatants and an increase in IL-1 receptor expression on the cell surface (p<0.05).

Fluoro-2-deoxy-D-glucose (FDG)-PET in APOEepsilon4 carriers in the Australian population.

Science.gov (United States)

Rimajova, Mira; Lenzo, Nat P; Wu, Jing-Shan; Bates, Kristyn A; Campbell, Andrew; Dhaliwal, Satvinder S; McCarthy, Michael; Rodrigues, Mark; Paton, Athena; Rowe, Christopher; Foster, Jonathan K; Martins, Ralph N

2008-03-01

Apolipoprotein E-epsilon4 (APOEepsilon4) has been associated with increased risk of developing Alzheimer's disease (AD) and regional cerebral glucose hypometabolism, as measured by fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET). We report here preliminary data from studies that aim to determine whether cerebral glucose hypometabolism is observed in APOEepsilon4 positive, cognitively intact individuals between the ages of 50 and 80, and whether there is an additional impact of subjective memory complainer (SMC) status on glucose metabolism determined by NeuroStat analysis. FDG-PET was conducted in 30 community dwelling, APOE-epsilon4 carriers without clinical evidence of dementia and objective cognitive impairment as assessed using a neuropsychological battery. Neurological soft-signs (NSS) were also assessed. Glucose hypometabolism was demonstrated in the anterior and posterior cingulate cortex and in the temporal association cortices in APOEepsilon4 carriers compared to the normative NeuroStat database. This pattern was particularly evident in APOEepsilon4 heterozygous individuals. SMC showed hypometabolism in the aforementioned brain regions, whereas non-SMC showed no significant pattern of glucose hypometabolism. FDG-PET with NeuroStat analysis showed that APOEepsilon4 carriers have mild glucose hypometabolism in areas associated with AD. SMC may be associated with AD-related differences in regional cerebral glucose metabolism. These findings are currently being investigated in a larger group of APOEepsilon4 carriers.

Fluoro-deoxy-D-glucose: biological behaviour, significance and interest

International Nuclear Information System (INIS)

Vuillez, J.P.

2001-01-01

Fluorine 18-labelled fluoro-deoxy-D-glucose (FDG) demonstrated a growing interest in oncology during the fifteen past years. Biological mechanisms of its tumour uptake are well known, but uptake intensity depends on numerous factors related to cellular metabolism, tumour characteristics and environment, patient and treatments. Thus the significance of scintigraphic images and moreover their clinical interest require detailed semeiologic analysis which takes into account these factors, in order to make the best use of the FDG for the detection of lesions and recurrences, and for treatment response evaluation. (author)

Brain metabolic changes in Hodgkin disease patients following diagnosis and during the disease course: An 18F-FDG PET/CT study.

Science.gov (United States)

Chiaravalloti, Agostino; Pagani, Marco; Cantonetti, Maria; DI Pietro, Barbara; Tavolozza, Mario; Travascio, Laura; DI Biagio, Daniele; Danieli, Roberta; Schillaci, Orazio

2015-02-01

The aim of the present study was to investigate brain glucose metabolism in patients with Hodgkin disease (HD) after diagnosis and during chemotherapy treatment. Following the administration of first-line doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy, 74 HD patients underwent 18 F-fluoro-2-deoxy-D-glucose ( 18 F-FDG) positron emission tomography (PET)/computed tomography brain scans, both baseline (PET0) and interim (PET2) at the Department of Biomedicine and Prevention, University of Rome Tor Vergata (Rome, Italy). Fifty-seven patients were further evaluated 15±6 days after four additional cycles (PET6). Furthermore, a control group (CG) of 40 chemotherapy-naïve subjects was enrolled. Differences in brain 18 F-FDG uptake between the CG, PET0, PET2 and PET6 scans were analyzed using statistical parametric mapping. Compared with the PET0 and CG scans, the PET2 scan demonstrated a higher metabolic activity in Brodmann area (BA) 39, and a metabolic reduction in BA 11 bilaterally and in left BA 32. All of these changes disappeared at PET6. The results of the present study indicate that ABVD chemotherapy has a limited impact on brain metabolism.

Significance of 18F-2-deoxy-2-fluoro-glucose accumulation in the stomach on positron emission tomography

International Nuclear Information System (INIS)

Takahashi, Hiroshi; Ukawa, Kunio; Ohkawa, Nobuhiko

2009-01-01

To explain the accumulation of 18 F-2-deoxy-2-fluoro-glucose ( 18 FDG) on positron emission tomography (PET) in the stomach and differences in its pattern, we focus on the accumulation pattern in association with endoscopic findings of the gastric mucosa and Helicobacter pylori (Hp) infection. Of 599 cases undergoing 18 FDG-PET examinations, we retrospectively analyzed the pattern of 18 FDG accumulation in the stomach, findings of upper gastrointestinal endoscopy, and Hp infection. The pattern of 18 FDG accumulation was classified into three groups: localized accumulation only in the fornix (Group A, 32 patients), diffuse accumulation throughout the entire stomach (Group B, 49 patients), and no accumulation (Group C, 191 patients). Regarding the relation between Hp infection and 18 FDG accumulation, Hp infection was positive in 56.3% of Group A, 73.5% of Group B, and 24.1% of Group C, with significant differences (p 18 FDG accumulation and gastric mucosal inflammation, when Groups A and B were compared with Group C, nearly half of the cases in the former groups had papular redness with a significantly higher frequency of redness and erosion. Three cases found to have malignant tumor were limited to the former groups. One mucosa-associated lymphoid tissue (MALT) lymphoma case was also found in the same group. Accumulation of 18 FDG largely corresponded to mucosal inflammation including superficial gastritis and erosive gastritis, and therefore the main cause of non-specific 18 FDG accumulation was considered to be inflammatory mucosa (mainly redness). The accumulation pattern was not associated with atrophic changes of the gastric mucosa or with Hp infection, but with mucosal inflammatory changes, including redness and erosion localized to the fornix. Accumulation of 18 FDG in the stomach suggests a high probability of the presence of inflammatory change in the gastric mucosa forming a background for the development of cancer or malignant lymphoma, and thus requires

The role of 18F-fluoro-2-deoxyglucose positron emission tomography/computed tomography in the management of patients with carcinoma of unknown primary.

Science.gov (United States)

Deonarine, P; Han, S; Poon, F W; de Wet, C

2013-08-01

Carcinoma of unknown primary is one of the ten most frequent cancers worldwide. Its median survival time is less than 10 months. Detecting primary tumour locations and/or occult metastatic lesions may inform definitive treatment and improve patients' prognosis. We aimed to determine: (1) the sensitivity, specificity and accuracy of (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography; (2) its detection rate of primary tumour locations and occult metastases and (3) factors associated with improved survival times. We retrospectively reviewed all cases in the West of Scotland for the period 1 December 2007 to 31 May 2011 that met all our selection criteria: (1) diagnosis of carcinoma of unknown primary; (2) a thorough but negative 'work-up' and (3) (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography report. Statistical methods included frequencies, Kaplan-Meier graphs and log-rank tests to compare survival times. (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography detected primary tumour sites in 19/51 (37.3%) and occult metastases in 28/51 (54.9%) of eligible patients. Its sensitivity, specificity and accuracy were 79.2%, 70.4% and 74.5%, respectively; 20/51 (39.2%) patients died during the study period with a median survival of 8.4 months (range 21.4, SD ± 6.2). The number of metastatic locations was strongly associated with survival (p = 0.002), but detection of a primary tumour site (p = 0.174) or histopathology (p = 0.301) was not. (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography detected occult metastatic sites in the majority and a primary cancer location in a substantial minority of patients. Our results were comparable with international literature and may indicate that (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography have an early role to improve the accuracy of cancer staging and to optimise carcinoma of unknown

Clinical studies for improving radiotherapy with 2-deoxy-D-glucose: Present status and future prospects

Directory of Open Access Journals (Sweden)

Dwarakanath B

2009-09-01

Full Text Available Higher rates of glucose usage generally correlate with poor prognosis in several types of malignant tumours. Experimental studies (both in vitro and in vivo have shown that 2-deoxy-D-glucose (2-DG, a glucose analog and glycolytic inhibitor, enhances radiation-induced damage selectively in tumor cells while protecting normal cells, thereby suggesting that 2-DG can be used as a differential radiomodifier to improve the efficacy of radiotherapy. Clinical trials undertaken to study the feasibility, safety, and validity of this suggested approach will be described. Based on 2-DG-induced radiosensitization observed in primary organ cultures of cerebral glioma tissues, clinical trials were designed taking into consideration the radiobiology of gliomas and pharmacokinetics of 2-DG. Phase I/II clinical trials have unequivocally demonstrated that a combination of 2-DG (200-300 mg 2-DG per kg body weight orally administered after overnight fasting, 20min before irradiation with large weekly fractions (5 Gy/fraction of low-LET radiotherapy is well tolerated without any acute toxicity or late radiation damage to the normal brain tissue. Nonserious transient side effects similar to hypoglycemia induced disturbances like restlessness, nausea, and vomiting were observed at the 2-DG doses used. Data from these trials involving more than 100 patients have clearly indicated a moderate increase in the survival, with a significant improvement in the quality of life with clinicopathological evidence of protection of normal brain tissue. A phase III multicentric trial to evaluate the efficacy of the combined treatment is in progress. Directions for future studies are discussed.

Parametric imaging of {sup 18}F-fluoro-3-deoxy-3-l-fluorothymidine PET data to investigate tumour heterogeneity

Energy Technology Data Exchange (ETDEWEB)

Veronese, M. [University of Padova, Department of Information Engineering (DEI), Padova (Italy); King' s College London, Department of Neuroimaging, Institute of Psychiatry, London (United Kingdom); Rizzo, G.; Bertoldo, A. [University of Padova, Department of Information Engineering (DEI), Padova (Italy); Aboagye, E.O. [Imperial College London, Comprehensive Cancer Imaging Centre, London (United Kingdom)

2014-09-15

[{sup 18}F]Fluoro-3'-deoxy-3'-l-fluorothymidine ([{sup 18}F]FLT) is a tissue proliferation marker which has been widely validated as a tumour-specific imaging tracer for PET. [{sup 18}F]FLT uptake in breast cancer is generally quantified at the region level or through first-order statistical descriptors (mean or maximum value), approaches that ignore the known complexity and heterogeneity of cancer tissues. Our aims were: (1) to validate a robust and reproducible voxel-wise approach to the quantification of [{sup 18}F]FLT PET data in breast cancer patients, and (2) to exploit the entire distribution of the [{sup 18}F]FLT retention estimates and their variability in the tumour region for the prediction of early treatment response. The dataset was derived from 15 patients with stage II-IV breast cancer, scanned twice before chemotherapy and once 1 week after therapy. Using RECIST criteria (after 60 days) nine patients were categorized as responders or nonresponders to treatment. Kinetic modelling (compartmental modelling, Patlak analysis and spectral analysis with iterative filter), tissue-to-plasma ratio and standardized uptake value were applied at the voxel level. Test-retest estimates were used to assess reproducibility and reliability of the [{sup 18}F]FLT uptake values before and after therapy for responder/nonresponder prediction. All the methods provided a measure of [{sup 18}F]FLT uptake that was reliable and reproducible with ICC >0.94. Moreover, a very strong correlation was found among the methods (R {sup 2} > 0.81). All the methods provided a limited number of outliers (<20 % in tumour), with the exception of compartmental modelling (>25 %) which was therefore excluded from the prediction analysis. Differences between before and after therapy in mean voxel-wise uptake in tumour did not allow a complete responder/nonresponder classification. In contrast, considering the full estimate distributions within the tumour (changes in median and mode

Synthesis procedure for routine production of 2-[{sup 18}F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[{sup 18}F]F-A-85380)

Energy Technology Data Exchange (ETDEWEB)

Schildan, Andreas [Department of Nuclear Medicine, University of Leipzig, 04103 Leipzig (Germany)], E-mail: andreas.schildan@medizin.uni-leipzig.de; Patt, Marianne; Sabri, Osama [Department of Nuclear Medicine, University of Leipzig, 04103 Leipzig (Germany)

2007-11-15

2-[{sup 18}F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[{sup 18}F]F-A-85380) was among the first subtype selective radioligands to visualise the in vivo distribution of {alpha}4{beta}2-containing neuronal nicotinic acetylcholine receptors (nAChRs) in human brain. We developed a one-pot synthesis for the preparation of 2-[{sup 18}F]F-A-85380 in a commercially available TRACERlab FX{sub F-N} synthesis module. The synthesis comprises a nucleophilic substitution followed by hydrolysis of a t-butyloxycarbonyl (BOC)-protected intermediate. After formulation for intravenous application up to 20 GBq 2-[{sup 18}F]F-A-85380 were produced from a starting activity of 100 GBq [{sup 18}F]fluoride in 60 min with a specific activity of about 4.10{sup 5} GBq/mmol and a mean radiochemical purity of more than 99%.

Is enteral administration of fluorine-18-fluorodeoxyglucose (F-18 FDG) a palatable alternative to IV injection? Pre-clinical evaluation in normal rodents

Energy Technology Data Exchange (ETDEWEB)

Higashi, T. E-mail: higashi@kuhp.kyoto-u.ac.jp; Fisher, S.J.; Nakada, K.; Romain, D.J.; Wahl, R.L

2002-04-01

To establish effective methods of enteral 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) administration, the efficiency of FDG absorption in the gastrointestinal tracts following enteral administrations was evaluated using the FDG biodistribution in normal rodents, in combination with various fasting conditions and FDG diluents. The blood FDG curve using hypotonic solution showed a rapid increase, while that in iso- and hypertonic groups showed slow rises. Brain FDG uptake had a close positive correlation with blood AUC (area under curve) and an inverse relationship with the stomach contents.

Is enteral administration of fluorine-18-fluorodeoxyglucose (F-18 FDG) a palatable alternative to IV injection? Pre-clinical evaluation in normal rodents

International Nuclear Information System (INIS)

Higashi, T.; Fisher, S.J.; Nakada, K.; Romain, D.J.; Wahl, R.L.

2002-01-01

To establish effective methods of enteral 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) administration, the efficiency of FDG absorption in the gastrointestinal tracts following enteral administrations was evaluated using the FDG biodistribution in normal rodents, in combination with various fasting conditions and FDG diluents. The blood FDG curve using hypotonic solution showed a rapid increase, while that in iso- and hypertonic groups showed slow rises. Brain FDG uptake had a close positive correlation with blood AUC (area under curve) and an inverse relationship with the stomach contents

An autosynthesizer for 2-[fluorine-18]fluoro-2-deoxy-d-glucose

International Nuclear Information System (INIS)

Maeder, T.; Scherer, U.W.; Weinreich, R.; Schmid, N.

1992-01-01

[ 18 F]2-FDG as an important reagent for PET users is produced successfully in various apparatus all over the world. However most of these automated synthesizers are delicate, high-tech scientific machines with features that are not absolutely necessary for routine. The goal of our development project was to create a reliable, simple to operate and low cost autosynthesizer which requires a minimum of maintenance. Some new and unconventional units had to be developed to reduce mechanical movement and eliminate the need to handle the liquids for heating and cooling, or periodic manual cleaning steps. (author) 8 figs., 2 refs

2-deoxy-D-glucose-induced metabolic stress enhances resistance to Listeria monocytogenes infection in mice

Science.gov (United States)

Miller, E. S.; Bates, R. A.; Koebel, D. A.; Fuchs, B. B.; Sonnenfeld, G.

1998-01-01

Exposure to different forms of psychological and physiological stress can elicit a host stress response, which alters normal parameters of neuroendocrine homeostasis. The present study evaluated the influence of the metabolic stressor 2-deoxy-D-glucose (2-DG; a glucose analog, which when administered to rodents, induces acute periods of metabolic stress) on the capacity of mice to resist infection with the facultative intracellular bacterial pathogen Listeria monocytogenes. Female BDF1 mice were injected with 2-DG (500 mg/kg b. wt.) once every 48 h prior to, concurrent with, or after the onset of a sublethal dose of virulent L. monocytogenes. Kinetics of bacterial growth in mice were not altered if 2-DG was applied concurrently or after the start of the infection. In contrast, mice exposed to 2-DG prior to infection demonstrated an enhanced resistance to the listeria challenge. The enhanced bacterial clearance in vivo could not be explained by 2-DG exerting a toxic effect on the listeria, based on the results of two experiments. First, 2-DG did not inhibit listeria replication in trypticase soy broth. Second, replication of L. monocytogenes was not inhibited in bone marrow-derived macrophage cultures exposed to 2-DG. Production of neopterin and lysozyme, indicators of macrophage activation, were enhanced following exposure to 2-DG, which correlated with the increased resistance to L. monocytogenes. These results support the contention that the host response to 2-DG-induced metabolic stress can influence the capacity of the immune system to resist infection by certain classes of microbial pathogens.

The efficacy of preoperative positron emission tomography-computed tomography (PET-CT) for detection of lymph node metastasis in cervical and endometrial cancer: clinical and pathological factors influencing it.

Science.gov (United States)

Nogami, Yuya; Banno, Kouji; Irie, Haruko; Iida, Miho; Kisu, Iori; Masugi, Yohei; Tanaka, Kyoko; Tominaga, Eiichiro; Okuda, Shigeo; Murakami, Koji; Aoki, Daisuke

2015-01-01

We studied the diagnostic performance of (18)F-fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography in cervical and endometrial cancers with particular focus on lymph node metastases. Seventy patients with cervical cancer and 53 with endometrial cancer were imaged with (18)F-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography before lymphadenectomy. We evaluated the diagnostic performance of (18)F-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography using the final pathological diagnoses as the golden standard. We calculated the sensitivity, specificity, positive predictive value and negative predictive value of (18)F-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography. In cervical cancer, the results evaluated by cases were 33.3, 92.7, 55.6 and 83.6%, respectively. When evaluated by the area of lymph nodes, the results were 30.6, 98.9, 55.0 and 97.0%, respectively. As for endometrial cancer, the results evaluated by cases were 50.0, 93.9, 40.0 and 95.8%, and by area of lymph nodes, 45.0, 99.4, 64.3 and 98.5%, respectively. The limitation of the efficacy was found out by analyzing it by the region of the lymph node, the size of metastatic node, the historical type of tumor in cervical cancer and the prevalence of lymph node metastasis. The efficacy of positron emission tomography/computed tomography regarding the detection of lymph node metastasis in cervical and endometrial cancer is not established and has limitations associated with the region of the lymph node, the size of metastasis lesion in lymph node and the pathological type of primary tumor. The indication for the imaging and the interpretation of the results requires consideration for each case by the pretest probability based on the information obtained preoperatively. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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)

Radiochemistry on chip : towards dose-on-demand synthesis of PET radiopharmaceuticals

NARCIS (Netherlands)

Arima, V.; Pascali, G.; Lade, O.; Kretschmer, H.R.; Bernsdorf, I.; Hammond, V.; Watts, P.; De Leonardis, F.; Tarn, M.D.; Pamme, N.; Cvetkovic, B.Z.; Dittrich, P.S.; Vasovic, N.; Duane, R.; Jaksic, A.; Zacheo, A.; Zizzari, A.; Marra, L.; Perrone, E.; Salvadori, P.A.; Rinaldi, R.

2013-01-01

We have developed an integrated microfluidic platform for producing 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) in continuous flow from a single bolus of radioactive isotope solution, with constant product yields achieved throughout the operation that were comparable to those reported for

Clinical Value of Coincidence Detection Emission Tomography Using Fluoine-18-2-Fluoro-2-Deoxy-D-Glucose in the Diagnosis of Solitary Pulmonary Nodules: Correlation with Computed Tomography Findings

International Nuclear Information System (INIS)

Najjar, F.; Moretti, J.

2007-01-01

Solitary Pulmonary Nodules (size 40 mm) is the most frequent indication of coincidence detection emission tomography (CDET) with fluorine-18 fluoro-2-deoxy-D-glucose (18FDG). The aim of the present study was to establish the efficacy of this system with and without attenuation correction (AC) in correlation with computed tomography (CT) findings for the distinction between benign and malignant pulmonary nodules. Material and methods: Sixty-eight patients were included in this study. All patients presented with suspected pulmonary nodules on thoracic CT. In addition, they had CDET scan using a dual-head coincidence gamma-camera with and without measured attenuation using caesium- 137 source. Corrected images were independently interpreted from non-attenuation corrected images in a blinded manner of any clinical data. 18FDG-CDET findings were evaluated by histology when it was available. Otherwise, the final clinical outcome has been considered in data analysis. Results: A total of 71 suspected nodules were observed by CT. Malignant pulmonary disease was found in 38 of these nodules whereas 33 pulmonary nodules were proved to be benign. In addition, one malignant nodule was confirmed with negative CT findings. 18FDG-CDET imaging without AC demonstrated 48 suspected pulmonary lesions included 4 nodules with negative CT findings (sensitivity, 92%; specificity, 68.4%) Versus 43 lesions identified with AC (sensitivity, 92%; specificity, 81.5%). All of the malignant nodules >20 mm in diameter by 18FDG-CDET. In 5 patients (8% of cases), uncorrected images were spotting benign nodules which were considered as negative on corrected images. So lower specificity rate was obtained by non AC mode in comparison with AC mode (68.4% versus 81.5% respectively). Both modalities techniques failed to detect malignancy in 3 patients. In general, the diagnostic accuracy of 18FDG-CDET without AC was relatively comparable to that found with AC (82.6% to 87%, respectively).

Influence of 2-(18F) fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography on recurrent ovarian cancer diagnosis and on selection of patients for secondary cytoreductive surgery

DEFF Research Database (Denmark)

Risum, Signe; Høgdall, Claus; Markova, Elena

2009-01-01

physical examination, US, or increasing cancer antigen 125 (CA125) level (>50 U/mL or >15% above baseline level). Recurrent OC was diagnosed 58 times in 52 patients. The sensitivities of US, CT, and PET/CT for diagnosing recurrence were 66% (P = 0.003), 81% (P = 0.0001), and 97% (P ...The objective of this prospective study was to compare the sensitivities and the specificities of combined 2-(F) fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (PET/CT), abdominal/transvaginal ultrasound (US), and CT for diagnosing recurrent ovarian cancer (OC......) and to evaluate the influence of PET/CT on referral of patients with solitary recurrence to secondary cytoreductive surgery. From April 2005 to November 2007, 60 patients were consecutively included to PET/CT 68 times. The inclusion criteria were remission of 3 months or longer and recurrent OC suspected from...

Purification, crystallization and preliminary X-ray analysis of rice BGlu1 β-glucosidase with and without 2-deoxy-2-fluoro-β-d-glucoside

International Nuclear Information System (INIS)

Chuenchor, Watchalee; Pengthaisong, Salila; Yuvaniyama, Jirundon; Opassiri, Rodjana; Svasti, Jisnuson; Ketudat Cairns, James R.

2006-01-01

Rice BGlu1 β-glucosidase was purified from recombinant E. coli and crystallized with and without the inhibitor 2-deoxy-2-fluoro-β-d-glucose. The crystals diffracted to 2.15 and 2.75 Å, respectively. Rice (Oryza sativa) BGlu1 β-glucosidase was expressed in Escherichia coli with N-terminal thioredoxin and hexahistidine tags and purified by immobilized metal-affinity chromatography (IMAC). After removal of the N-terminal tags, cation-exchange and S-200 gel-filtration chromatography yielded a 50 kDa BGlu1 with >95% purity. The free enzyme and a complex with 2,4-dinitrophenyl-2-deoxy-2-fluoro-β-d-glucopyranoside inhibitor were crystallized by microbatch and hanging-drop vapour diffusion. Small tetragonal crystals of BGlu1 with and without inhibitor grew in 18%(w/v) PEG 8000 with 0.1 M sodium cacodylate pH 6.5 and 0.2 M zinc acetate. Crystals of BGlu1 with inhibitor were streak-seeded into 23%(w/v) PEG MME 5000, 0.2 M ammonium sulfate, 0.1 M MES pH 6.7 to yield larger crystals. Crystals with and without inhibitor diffracted to 2.15 and 2.75 Å resolution, respectively, and had isomorphous orthorhombic unit cells belonging to space group P2 1 2 1 2 1

Detection of N-(1-deoxy-d-fructos-1-yl) Fumonisins B2 and B3 in Corn by High-Resolution LC-Orbitrap MS

Science.gov (United States)

Matsuo, Yosuke; Takahara, Kentaro; Sago, Yuki; Kushiro, Masayo; Nagashima, Hitoshi; Nakagawa, Hiroyuki

2015-01-01

The existence of glucose conjugates of fumonisin B2 (FB2) and fumonisin B3 (FB3) in corn powder was confirmed for the first time. These “bound-fumonisins” (FB2 and FB3 bound to glucose) were identified as N-(1-deoxy-d-fructos-1-yl) fumonisin B2 (NDfrc-FB2) and N-(1-deoxy-d-fructos-1-yl) fumonisin B3 (NDfrc-FB3) respectively, based on the accurate mass measurements of characteristic ions and fragmentation patterns using high-resolution liquid chromatography-Orbitrap mass spectrometry (LC-Orbitrap MS) analysis. Treatment on NDfrc-FB2 and NDfrc-FB3 with the o-phthalaldehyde (OPA) reagent also supported that d-glucose binding to FB2 and FB3 molecules occurred to their primary amine residues. PMID:26389955

1-[18F]fluoro-2-propanol p-toluenesulfonate: a synthon for the preparation of N-([18F]fluoroisopropyl)amines

International Nuclear Information System (INIS)

Groot, T.J. de; Elsinga, P.H.; Visser, G.M.; Vaalburg, W.

1992-01-01

The new radiochemical synthon 1-[ 18 F]fluoro-2-propanol p-toluenesulfonate is prepared with a radiochemical yield of 45% [corrected for decay to beginning of synthesis, synthesis time 40 min]. This compound is used to prepare the [ 18 F]fluoroisopropyl-alkylated derivatives of benzylamine and norephedrine with a yield of 7 and 2% respectively, (synthesis time 90 min). This alkylation reaction a good perspective for the preparation of [ 18 F]fluoro-labelled analogues of β 1 -adrenergic receptor binding ligands for PET. (Author)

Three-dimensional patterns of speech-induced cerebral and cerebellar activation in healthy volunteers and in aphasic stroke patients studied by positron emission tomography of 2(18F)-fluorodeoxyglucose

International Nuclear Information System (INIS)

Pawlik, G.; Heiss, W.D.; Beil, C.; Gruenewald, G.; Herholz, K.; Wienhard, K.; Wagner, R.

1987-01-01

Eight healthy male volunteers and eight moderately aphasic patients with a single cerebral infarctions in the postacute stage, were studied by dynamic positron emission tomography (PET) using the 2(18F)-fluoro-2-deoxy-D-glucose method and a 7-slice positron camera. Because hemispheric speech dominance is commonly thought to be closely related to handedness, subjects were tested by the Oldfield and Bryden questionnaires; the volunteers also had a tracking and pin-sort test. PET studies were performed in random order, both at rest and during spontaneous speech of rather abstract and some biographic content, with a time interval of 2 to 7 days between measurements of the same individual. Data was analyzed by means of weighted, repeated measures of analysis of variance (ANOVA). 11 refs.; 2 figs

Opsoclonus-induced occipital deactivation with a region-specific distribution

NARCIS (Netherlands)

de Jong, BM; van Weerden, TW; Haaxma, R

The cerebral distribution of 2-[18F]fluoro 2-deoxy-D-glucose (FDG) uptake in a patient with opsoclonus was measured by positron emission tomography (PET) and subsequently compared with the distribution in ten normal subjects. Statistical parametric mapping (SPM) revealed a decreased occipital FDG

Simultaneous analysis of FDG, ClDG and Kryptofix 2.2.2 in [18F]FDG preparation by high-performance liquid chromatography with UV detection

International Nuclear Information System (INIS)

Nakao, Ryuji; Ito, Takehito; Yamaguchi, Masatoshi; Suzuki, Kazutoshi

2008-01-01

A practical, sensitive and rapid analytical method was established and validated for chemical impurity tests of 2-deoxy-2-fluoro-D-glucose (FDG), 2-deoxy-2-chloro-D-glucose (ClDG) and Kryptofix 2.2.2 (K-222) in [ 18 F]FDG. This method was based on precolumn derivatization with ultraviolet (UV) detection. FDG and ClDG were rapidly derivatized with 1-phenyl-3-methyl-5-pyrazolone in the presence of borate buffer at 40 o C, and the labeled derivatives and K-222 were separated by reversed-phase high-performance liquid chromatography and monitored by UV absorbance at 210 nm. After optimization of the conditions, FDG, ClDG and K-222 could be determined within 15 min and showed good performance in terms of sensitivity, linearity and reproducibility. This method could be successfully applied to the quality control test of [ 18 F]FDG produced by a commercially available apparatus

Evaluation of outcome prediction and disease extension by quantitative 2-deoxy-2-[18F] fluoro-D-glucose with positron emission tomography in patients with small cell lung cancer

International Nuclear Information System (INIS)

Arslan, N.; Tuncel, M.; Kuzhan, O.; Alagoz, E.; Budakoglu, B.; Ozet, A.; Ozguven, M.A.

2011-01-01

The objective of this study is to determine whether 2-deoxy-2-[18F] fluoro-D-glucose with positron emission tomography (FDG-PET) imaging and quantitative PET parameters can predict outcome and differentiate patients with limited disease (LD) from extensive disease (ED) in patients with small cell lung cancer (SCLC). We retrospectively evaluated data from 25 patients who underwent either initial staging (Group A, n 12) or restaging (Group B, n 13) by conventional imaging methods and FDG-PET according to the simplified staging scheme developed by the Veterans Administration Lung Cancer Study Group-2. FDG-PET images were both visually and quantitatively evaluated with standardized uptake value (SUV) max , SUV ave , total metabolic tumor volume (with SUV max >%50 and SUV max >2.5), total lesion glycolysis (TLG) (with SUV max >%50 and SUV max >2.5). The correlation between quantitative PET parameters, disease stages and survival were analyzed. By conventional methods 14 of 25 (56%) patients were reported to have LD and 11 of 25 (44%) had ED. FDG-PET scan upstaged 9 out of 25 (36%) and downstaged 2 out of 25 (%8) patients. Among the quantitative PET parameters, TLGs were the only PET parameters that differentiated between Group A and Group B patients. FDG-PET staging (p=0.019) could predict significant survival difference between stages on contrary to conventional staging (p=0.055). Moreover, TLG [SUV max >%50] was the only quantitative PET parameter that could predict survival (p=0.027). FDG-PET imaging is a valuable tool in the management of patients with SCLC for a more accurate staging. The use of quantitative PET parameters may have a role in prediction of stage and survival. (author)

Role of fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography in the evaluation of axillary lymph node involvement in operable breast cancer in comparison with sentinel lymph node biopsy

International Nuclear Information System (INIS)

Challa, Vasu Reddy; Srivastava, Anurag; Dhar, Anita; Parshad, Rajinder; Bal, Chandrasekhar; Gona, Rama Mohan Reddy; Kumar, Rakesh; Sharma, Punit; Gupta, Siddhartha Datta

2013-01-01

Role of (18(F)fluorine-18-labeled 2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography-computed tomography (PET-CT) in the evaluation of axillary lymph node involvement in T1T2N0 breast cancer and compare results with sentinel lymph node biopsy (SLNB). SLN was identified in 32 of 37 patients with an identification rate of 86.48% (32/37). With combined technique SLN identification rate was 100% (6/6) while with blue dye alone; it was 83.8% (26/31). Among 37 patients, 16 had axillary metastases of which 12 had macrometastases and four had micrometastases detected by immunohistochemistry (IHC). Of 12 patients with axillary macrometastases, skip metastases were present in two patients in whom SLN was negative and in two patients SLN was not identified, but axillary dissection showed metastases. PET-CT had shown sensitivity, specificity, negative predictive value and positive predictive value of 56%, 90%, 73%, and 81.8%, respectively. IHC of SLN detected four patients with micrometastases upstaging the disease by 11% (4/37). Because FDG PET-CT has a high specificity in the evaluation of axillary lymph node involvement in T1T2N0 breast cancer patients according to the results of this study if FDG PET-CT is positive in axillary lymph nodes, axillary lymph node dissection may be considered instead of SLNB

Callose deposition during gravitropism of Zea mays and Pisum sativum and its inhibition by 2-deoxy-D-glucose

Science.gov (United States)

Jaffe, M. J.; Leopold, A. C.

1984-01-01

In etiolated corn (Zea mays L.) and etiolated pea (Pisum sativum L.) seedlings, a gravitropic stimulation induces the deposition of callose. In the corn coleoptiles this occurs within 5 min of gravity stimulation, and prior to the beginning of curvature. Both gravitropic curvature and callose deposition reach their maxima by 12 h. Within the first 2 h more callose is deposited on the upper (concave) side, but after 2-3 h, this deposition pattern is reversed. An inhibitor of protein glycosylation, 2-deoxy-D-glucose (DDG), inhibits callose production and considerably retards gravitropic bending in both species of plants. Mannose can relieve the inhibition of gravitropic bending by DDG. The pea mutant "Ageotropum", which does not respond to gravity when etiolated, also fails to produce callose in response to a gravitic stimulus. These correlations indicate that callose deposition may be a biochemical component of gravitropism in plant shoots.

Hematoporphyrin derivatives potentiate the radiosensitizing effects of 2-deoxy-D-glucose in cancer cells

International Nuclear Information System (INIS)

Dwarakanath, B.S.; Adhikari, J.S.; Jain, Viney

1999-01-01

Purpose: Two deoxy-D-glucose (2-DG), an inhibitor of glucose transport and glycolysis, has been shown to differentially inhibit the repair of radiation damage in cancer cells by reducing the flow of metabolic energy. Since hematoporphyrin derivatives (Hpd) inhibit certain enzymes of the respiratory metabolism, resulting in an increase in the glucose usage and glycolysis, Hpd could possibly enhance the energy-linked radiosensitizing effects of 2-DG in cancer cells. The purpose of the present work was to verify this suggestion. Methods and Materials: Two human tumor cell lines (cerebral glioma, BMG-1 and squamous cell carcinoma, 4197) and a murine tumor cell line (Ehrlich ascites tumor [EAT], F-15) in vitro were investigated. A commercially available preparation of Hpd, Photosan-3 (PS-3) was used in the present studies. Cells incubated with 0-10 μg/ml PS-3 for 0-24 h before irradiation were exposed to 2.5 Gy of Co-60 gamma rays and maintained under liquid holding conditions for 1-4 h to facilitate repair. 2-DG (0-5 mM) added at the time of irradiation was present during the liquid holding. Radiation-induced cytogenetic damage (micronuclei formation) and cell death (macrocolony assay) were analyzed as parameters of radiation response. Effects of these radiosensitizers on glucose usage and glycolysis were also studied by measuring the glucose consumption and lactate production using enzymatic assays. Results: The glucose consumption and lactate production of BMG-1 cells (0.83 and 1.43 pmole/cell/h) were twofold higher than in the 4197 cells (0.38 and 0.63 pmole/cell/h). Presence of PS-3 (10 μg/ml) enhanced the rate of glycolysis (glucose consumption and lactate production) in these cells by 35% to 65%, which was reduced by 20% to 40% in the presence of 5 mM 2-DG. In exponentially growing BMG-1 and EAT cells, presence of 2-DG (5 mM; equimolar with glucose) for 4 hours after irradiation increased the radiation-induced micronuclei formation and cell death by nearly 40

FDG-PET/CT in the evaluation of anal carcinoma

International Nuclear Information System (INIS)

Cotter, Shane E.; Grigsby, Perry W.; Siegel, Barry A.

2006-01-01

Purpose: Surgical staging and treatment of anal carcinoma has been replaced by noninvasive staging studies and combined modality therapy. In this study, we compare computed tomography (CT) and physical examination to [ 18 F]-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in the staging of carcinoma of the anal canal, with special emphasis on determination of spread to inguinal lymph nodes. Methods and Materials: Between July 2003 and July 2005, 41 consecutive patients with biopsy-proved anal carcinoma underwent a complete staging evaluation including physical examination, CT, and 2-FDG-PET/CT. Patients ranged in age from 30 to 89 years. Nine men were HIV-positive. Treatment was with standard Nigro regimen. Results: [ 18 F]-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) detected 91% of nonexcised primary tumors, whereas CT visualized 59%. FDG-PET/CT detected abnormal uptake in pelvic nodes of 5 patients with normal pelvic CT scans. FDG-PET/CT detected abnormal nodes in 20% of groins that were normal by CT, and in 23% without abnormality on physical examination. Furthermore, 17% of groins negative by both CT and physical examination showed abnormal uptake on FDG-PET/CT. HIV-positive patients had an increased frequency of PET-positive lymph nodes. Conclusion: [ 18 F]-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography detects the primary tumor more often than CT. FDG-PET/CT detects substantially more abnormal inguinal lymph nodes than are identified by standard clinical staging with CT and physical examination

Synthesis of O-[2-[18F]fluoro-3-(2-nitro-1H-imidazole-1-yl)propyl]tyrosine ([18F]FNT]) as a new class of tracer for imaging hypoxia

International Nuclear Information System (INIS)

Noeen Malik; Xian Lin; Christoph Solbach; Hans-Juergen Machulla; Bin Shen; Gerald Reischl; Wolfgang Voelter

2012-01-01

For detection of hypoxic tumor tissue, all radiotracers synthesized until now, are based on the concept that cellular uptake is being controlled by diffusion. As a new approach, we chose the concept to have the tracer hypothetically transported into the cells by well known carrier systems like the amino acid transporters. For this purpose, radiosynthesis of O-[2-[ 18 F]fluoro-3-(2-nitro-1H-imidazole-1yl)propyl]tyrosine ([18F]FNT]) was carried out from methyl 2-(benzyloxycarbonyl)-3-(4-3-(2-nitro-1H-imidazol-1-yl) -2-(tosyloxy)propoxy) phenyl)propanoate via no-carrier-added nucleophilic aliphatic substitution. After labelling, 81 ± 0.9% of labelled intermediate i.e. methyl 2-(benzyloxycarbonyl)-3-(4-(2-[ 18 F]fluoro-3- (2-nitro-1H-imidazole-1-yl)propoxy) phenyl)propanoate was obtained at 140 deg C. At the end of radiosynthesis, [ 18 F]FNT was obtained in an overall radiochemical yield of 40 ± 0.9% (not decay corrected) within 90 min in a radiochemical purity of >98% in a formulation ready for application in the clinical studies for PET imaging of hypoxia. (author)

Chronic ingestion of 2-deoxy-D-glucose induces cardiac vacuolization and increases mortality in rats

International Nuclear Information System (INIS)

Minor, Robin K.; Smith, Daniel L.; Sossong, Alex M.; Kaushik, Susmita; Poosala, Suresh; Spangler, Edward L.; Roth, George S.; Lane, Mark; Allison, David B.; Cabo, Rafael de; Ingram, Donald K.; Mattison, Julie A.

2010-01-01

Calorie restriction (CR), the purposeful reduction of energy intake with maintenance of adequate micronutrient intake, is well known to extend the lifespan of laboratory animals. Compounds like 2-deoxy-D-glucose (2DG) that can recapitulate the metabolic effects of CR are of great interest for their potential to extend lifespan. 2DG treatment has been shown to have potential therapeutic benefits for treating cancer and seizures. 2DG has also recapitulated some hallmarks of the CR phenotype including reduced body temperature and circulating insulin in short-term rodent trials, but one chronic feeding study in rats found toxic effects. The present studies were performed to further explore the long-term effects of 2DG in vivo. First we demonstrate that 2DG increases mortality of male Fischer-344 rats. Increased incidence of pheochromocytoma in the adrenal medulla was also noted in the 2DG treated rats. We reconfirm the cardiotoxicity of 2DG in a 6-week follow-up study evaluating male Brown Norway rats and a natural form of 2DG in addition to again examining effects in Fischer-344 rats and the original synthetic 2DG. High levels of both 2DG sources reduced weight gain secondary to reduced food intake in both strains. Histopathological analysis of the hearts revealed increasing vacuolarization of cardiac myocytes with dose, and tissue staining revealed the vacuoles were free of both glycogen and lipid. We did, however, observe higher expression of both cathepsin D and LC3 in the hearts of 2DG-treated rats which indicates an increase in autophagic flux. Although a remarkable CR-like phenotype can be reproduced with 2DG treatment, the ultimate toxicity of 2DG seriously challenges 2DG as a potential CR mimetic in mammals and also raises concerns about other therapeutic applications of the compound.

Simple noninvasive quantification method for measuring myocardial glucose utilization in humans employing positron emission tomography and fluorine-18 deoxyglucose

International Nuclear Information System (INIS)

Gambhir, S.S.; Schwaiger, M.; Huang, S.C.; Krivokapich, J.; Schelbert, H.R.; Nienaber, C.A.; Phelps, M.E.

1989-01-01

To estimate regional myocardial glucose utilization (rMGU) with positron emission tomography (PET) and 2-[ 18 F]fluoro-2-deoxy-D-glucose (FDG) in humans, we studied a method which simplifies the experimental procedure and is computationally efficient. This imaging approach uses a blood time-activity curve derived from a region of interest (ROI) drawn over dynamic PET images of the left ventricle (LV), and a Patlak graphic analysis. The spillover of radioactivity from the cardiac chambers to the myocardium is automatically removed by this analysis. Estimates of rMGU were obtained from FDG PET cardiac studies of six normal human subjects. Results from this study indicate that the FDG time-activity curve obtained from the LV ROI matched well with the arterial plasma curve. The rMGU obtained by Patlak graphic analysis was in good agreement with direct curve fitting results (r = 0.90). The average standard error of the estimate of the Patlak rMGU was low (3%). These results demonstrate the practical usefulness of a simplified method for the estimation of rMGU in humans by PET. This approach is noninvasive, computationally fast, and highly suited for developing parametric images of myocardial glucose utilization rate

Reaction of Br/sub 3/. /sup 2 -/ with 2-deoxy-D-ribose. A preferred attack at C-1

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Parsons, B J; Schulte-Frohlinde, D; von Sonntag, C [Max-Planck-Institut fuer Kohlenforschung, Muelheim an der Ruhr (Germany, F.R.). Inst. fuer Strahlenchemie

1978-06-01

In the photolysis of 5-bromouracil containing DNA Br atoms are expected intermediates. In order to evaluate the possible site of attack of the Br atom at the sugar moiety of DNA the reaction of 2-deoxy-D-Ribose with the Br atom (complexed with two bromide ions) was investigated. Hydroxyl radicals generated by the radiolysis of N/sub 2/O saturated aqueous solutions were converted into Br/sub 3/./sup 2 -/-radicals by 1 M bromide ions. Br/sub 3/./sup 2 -/-reacts with 2-deoxy-D-ribose (k = 3.7 x 10/sup 4/M/sup -1/s/sup -1/, pulse radiolysis). The major product is 2-deoxy-D-erythro-pentonic acid (G = 2.4, ..gamma..-radiolysis). It is formed by hydrogen abstraction from C-1 and oxidation of this radical by other radicals. An alternative route via the radical at C-2 is neglible. It follows that Br/sub 3/./sup 2 -/ reacts preferentially at C-1 of 2-deoxy-D-ribose.

[18F]-Fluoro-Deoxy-Glucose Positron Emission Tomography Scan Should Be Obtained Early in Cases of Autoimmune Encephalitis

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C. R. Newey

2016-01-01

Full Text Available Introduction. Autoimmune encephalitis (AE is a clinically challenging diagnosis with nonspecific neurological symptoms. Prompt diagnosis is important and often relies on neuroimaging. We present a case series of AE highlighting the importance of an early [18F]-fluoro-deoxy-glucose positron emission tomography (FDG-PET scan. Methods. Retrospective review of seven consecutive cases of autoimmune encephalitis. Results. All patients had both magnetic resonance imaging (MRI and FDG-PET scans. Initial clinical presentations included altered mental status and/or new onset seizures. Six cases had serum voltage-gated potassium channel (VGKC antibody and one had serum N-methyl-D-aspartate (NMDA antibody. MRI of brain showed mesial temporal lobe hyperintensity in five cases of VGKC. The other two patients with VGKC or NMDA AE had restiform body hyperintensity on MRI brain or a normal MRI, respectively. Mesial temporal lobe hypermetabolism was noted in three cases on FDG-PET, despite initial unremarkable MRI. Malignancy workup was negative in all patients. Conclusion. A high index of suspicion for AE should be maintained in patients presenting with cognitive symptoms, seizures, and limbic changes on neuroimaging. In cases with normal initial brain MRI, FDG-PET can be positive. Additionally, extralimbic hyperintensity on MRI may also be observed.

[18F]-Fluoro-Deoxy-Glucose Positron Emission Tomography Scan Should Be Obtained Early in Cases of Autoimmune Encephalitis

Science.gov (United States)

Sarwal, A.; Hantus, S.

2016-01-01

Introduction. Autoimmune encephalitis (AE) is a clinically challenging diagnosis with nonspecific neurological symptoms. Prompt diagnosis is important and often relies on neuroimaging. We present a case series of AE highlighting the importance of an early [18F]-fluoro-deoxy-glucose positron emission tomography (FDG-PET) scan. Methods. Retrospective review of seven consecutive cases of autoimmune encephalitis. Results. All patients had both magnetic resonance imaging (MRI) and FDG-PET scans. Initial clinical presentations included altered mental status and/or new onset seizures. Six cases had serum voltage-gated potassium channel (VGKC) antibody and one had serum N-methyl-D-aspartate (NMDA) antibody. MRI of brain showed mesial temporal lobe hyperintensity in five cases of VGKC. The other two patients with VGKC or NMDA AE had restiform body hyperintensity on MRI brain or a normal MRI, respectively. Mesial temporal lobe hypermetabolism was noted in three cases on FDG-PET, despite initial unremarkable MRI. Malignancy workup was negative in all patients. Conclusion. A high index of suspicion for AE should be maintained in patients presenting with cognitive symptoms, seizures, and limbic changes on neuroimaging. In cases with normal initial brain MRI, FDG-PET can be positive. Additionally, extralimbic hyperintensity on MRI may also be observed. PMID:27559482

Western blot data using two distinct anti-O-GlcNAc monoclonal antibodies showing unique glycosylation status on cellular proteins under 2-deoxy-d-glucose treatment

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Tetsuya Okuda

2017-02-01

Full Text Available Protein modification by O-linked N-acetylglucosamine (O-GlcNAcylation is one of the post transcriptional modifications occurring on cellular proteins. This paper provides a data set relating to the O-GlcNAcylation of cellular proteins detected by RL2 and CTD110.6 antibodies, which are commonly used for detection of protein O-GlcNAcylation, in 2-deoxy-d-glucose (2DG-treated human teratocarcinoma NCCIT cells in support of the research article entitled “A novel, promoter-based, target-specific assay identifies 2-deoxy-d-glucose as an inhibitor of globotriaosylceramide biosynthesis” (Okuda et al., 2009 [1]. The main article described a suppressive effect of 2DG on an Sp1 target gene in NCCIT cells and discussed the relationship between the effect of 2DG and O-GlcNAcylation status of Sp1. The data in this paper complements this relationship by Western blotting and clearly showed that the 2DG treatment increased O-GlcNAcylation of cellular proteins in NCCIT cells, whereas the RL2 and CTD110.6 epitopes were detected in a different manner. The RL2 epitope was detected on Sp1 during 2DG treatment, and the level was transiently increased at 24 h. In contrast, the CTD110.6 epitope became detectable on Sp1 over 72 h after 2DG treatment, and then the other proteins containing CTD110.6 epitopes also appeared in the cell lysates and the anti-Sp1 antibody precipitates.

1-[[sup 18]F]fluoro-2-propanol p-toluenesulfonate: a synthon for the preparation of N-([[sup 18]F]fluoroisopropyl)amines

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Groot, T.J. de; Elsinga, P.H.; Visser, G.M.; Vaalburg, W. (Groningen Univ. (Netherlands). PET Center and GCCS)

1992-11-01

The new radiochemical synthon 1-[[sup 18]F]fluoro-2-propanol p-toluenesulfonate is prepared with a radiochemical yield of 45% [corrected for decay to beginning of synthesis, synthesis time 40 min]. This compound is used to prepare the [[sup 18]F]fluoroisopropyl-alkylated derivatives of benzylamine and norephedrine with a yield of 7 and 2% respectively, (synthesis time 90 min). This alkylation reaction a good perspective for the preparation of [[sup 18]F]fluoro-labelled analogues of [beta][sub 1]-adrenergic receptor binding ligands for PET. (Author).

Improving cancer therapy with 2-deoxy-D-glucose : past, present and the future

International Nuclear Information System (INIS)

Dwarakanath, B.S.

2014-01-01

Metabolic reprogramming involving high rates of glycolysis even in the presence of oxygen (Warburg's Effects), is a prominent phenotype of many tumors that facilitates cancer cell survival, proliferation and resistance to therapies. Mechanisms underlying this reprogramming include gene and mitochondrial mutations, alterations in metabolic enzymes and adaptation to the hypoxic tumor micro-milieu in case of solid tumors. Pharmacological agents targeting this phenotype have not made impact as a therapeutic. However, the glycolytic inhibitor 2-deoxy-D-glucose (2-DG), the widely investigated pharmacological agent has been established as an ideal adjuvant in the radio- and chemotherapy of tumors. In vitro studies with monolayer, spheroids and organ cultures have not only established the selective radio- and chemo-sensitization of tumor cells by 2-DG, but have also provided deep insight in to the underlying mechanisms. In vivo studies with animal tumors have shown heterogeneous response, which have been recently linked to immune modulations in the form of increased innate and adaptive immunity with enhanced memory response, depletion of T-regulatory cells as well as a shift from Th2 and Th17 to Th1 in the cytokine switching and macrophage stimulation. Clinical studies with 2-DG as an adjuvant in the radiotherapy have demonstrated feasibility, lack of acute or late toxicity and better quality of life, besides benefit in the local tumor control. Recent studies have shown the potential of 2-DG as an Energy Restriction Mimetic Agent (ERMA) impairing the process of induced tumorigenesis, which could be an attractive cancer preventive strategy. Dietary administration of 2-DG impairs the formation and growth of implanted tumour cells, as well as chemical and radiation-induced cancers in mice. Alterations in oxidative stress, immune status, angiogenesis and matrix metalloproteinase-9, appear to contribute to the impaired tumorigenesis and growth by dietary 2-DG. Prospective

Can FDG-PET/CT replace blind bone marrow biopsy of the posterior iliac crest in Ewing sarcoma?

NARCIS (Netherlands)

Kasalak, Omer; Glaudemans, Andor W. J. M.; Overbosch, Jelle; Jutte, Paul C.; Kwee, Thomas C.

OBJECTIVE: To determine and compare the value of (18)F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) to blind bone marrow biopsy (BMB) of the posterior iliac crest in detecting metastatic bone marrow involvement in newly diagnosed Ewing sarcoma. MATERIALS AND

Synthesis of P1-(11-phenoxyundecyl)-P2-(2-acetamido-2-deoxy-3-O-α-D-rhamnopyranosyl-α-D-glucopyranosyl) diphosphate and P1-(11-phenoxyundecyl)-P2-(2-acetamido-2-deoxy-3-O-β-D-galactopyranosyl-α-D-galactopyranosyl) diphosphate for the investigation of biosynthesis of O-antigenic polysaccharides in Pseudomonas aeruginosa and Escherichia coli O104.

Science.gov (United States)

Torgov, Vladimir; Danilov, Leonid; Utkina, Natalia; Veselovsky, Vladimir; Brockhausen, Inka

2017-12-01

Two new phenoxyundecyl diphosphate sugars were synthesized for the first time: P 1 -(11-phenoxyundecyl)-P 2 - (2-acetamido-2-deoxy-3-O-α-D-rhamnopyranosyl-α-D-glucopyranosyl) diphosphate and P 1 -(11-phenoxyundecyl)-P 2 -(2-acetamido-2-deoxy-3-O-β-D-galactopyranosyl-α-D-galactopyranosyl) diphosphate to study the third step of biosynthesis of the repeating units of O-antigenic polysaccharides in Pseudomonas aeruginosa and E.coli O104 respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

2-Deoxy-D-Glucose Modified Magnetic Nanoparticles with Dual Functional Properties: Nanothermotherapy and Magnetic Resonance Imaging.

Science.gov (United States)

Zhao, Lingyun; Zheng, Yajing; Yan, Hao; Xie, WenSheng; Sun, Xiaodan; Li, Ning; Tang, Jintian

2016-03-01

Superparamagnetic iron oxide nanoparticles (SPIONs) with appropriate surface chemistry have attracted wild attention in medical and biological application because of their current and potential usefulness such as magnetic resonance imaging (MRI) contrast enhancement, magnetic mediated hyperthermia (MMH), immunoassay, and in drug delivery, etc. In this study, we investigated the MRI contrast agents and MMH mediators properties of the novel 2-deoxy-D-glucose (2-DG) modified SPIONs. As a non-metabolizable glucose analogue, 2-DG can block glycolysis and inhibits protein glycosylation. Moreover, SPIONs coated with 2-DG molecules can be particularly attractive to resource-hungry cancer cells, therefore to realize the targeting strategy for the SPIONs. SPIONs with amino silane as the capping agent for amino-group surface modification were synthesized by the chemical co-precipitation method with modification. Glutaraldehyde was further applied as an activation agent through which 2-DG was conjugated to the amino-coated SPIONs. Physicochemical characterizations of the 2-DG-SPIONs, such as surface morphology, surface charge and magnetic properties were investigated by Transmission Electron Microscopy (TEM), ζ-Potential and Vibrating Sample Magnetometer (VSM), etc. Magnetic inductive heating characteristics of the 2-DG-SPIONs were analyzed by exposing the SPIONs suspension (magnetic fluid) under alternative magnetic field (AMF). U-251 human glioma cells with expression of glucose transport proteins type 1 and 3 (GLUT1 and GLUT 3), and L929 murine fibroblast cell as negative control, were employed to study the effect of 2-DG modification on the cell uptake for SPIONs. TEM images for ultra-thin sections as well as ICP-MS were applied to evaluate the SPIONs internalization within the cells. In vitro MRI was performed after cells were co-incubated with SPIONs and the T2 relaxation time was measured and compared. The results demonstrate that 2-DG-SPIONs were supermagnetic and in

In vivo evaluation of 2'-deoxy-2'-[{sup 18}F]fluoro-5-iodo-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]FIAU) and 2'-deoxy-2'-[{sup 18}F]fluoro-5-ethyl-1-{beta}-D-arabinofuranosyluracil ([{sup 18}F]FEAU) as markers for suicide gene expression

Energy Technology Data Exchange (ETDEWEB)

Alauddin, Mian M. [University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd. T8.3895, P.O. Box 059, Houston, TX (United States); Shahinian, Antranic; Park, Ryan; Fissekis, John D.; Conti, Peter S. [University of Southern California, PET Imaging Science Center, Keck School of Medicine, Los Angeles, CA (United States); Tohme, Michel [University of Southern California, PET Imaging Science Center, Keck School of Medicine, Los Angeles, CA (United States); Department of Biomedical Engineering, UC Davis, Davis, CA (United States)

2007-06-15

FIAU and FEAU were evaluated in vitro and in vivo as markers for HSV1-tk gene expression. In vitro and biodistribution studies were performed in wild type and transduced HT-29 cells using [{sup 14}C]FIAU and [{sup 3}H]FEAU. PET imaging was performed using [{sup 18}F]FIAU and [{sup 18}F]FEAU. In vitro uptake of [{sup 14}C]FIAU in tk-positive cells was 39-fold, 49-fold, and 43-fold higher (p < 0.001) than in wild type cells at 30, 60, and 120 min, respectively. Uptake of [{sup 3}H]FEAU in transduced cells was 46-fold, 62-fold, and 121-fold higher (p < 0.001) than in wild type cells at the same time points. In vivo uptake of [{sup 14}C]FIAU at 2 h in HSV1-tk positive tumors was 15.48 {+-} 3.94, 6.7-fold higher (p < 0.001) than in wild type tumors. Uptake of [{sup 3}H]FEAU in transduced tumors was 9.98 {+-} 1.99, 5.0-fold higher (p < 0.001) than in wild type tumors. Micro-PET images using [{sup 18}F]FIAU and [{sup 18}F]FEAU also showed very high uptake in HSV-tk tumors. [{sup 18}F]FIAU and [{sup 18}F]FEAU appear to be potential PET imaging agents for gene expression. (orig.)

Comparative Oncology: Evaluation of 2-Deoxy-2-[18F]fluoro-D-glucose (FDG Positron Emission Tomography/Computed Tomography (PET/CT for the Staging of Dogs with Malignant Tumors.

Directory of Open Access Journals (Sweden)

Stefanie M F Seiler

Full Text Available 2-Deoxy-2-[18F]fluoro-D-glucose PET/CT is a well-established imaging method for staging, restaging and therapy-control in human medicine. In veterinary medicine, this imaging method could prove to be an attractive and innovative alternative to conventional imaging in order to improve staging and restaging. The aim of this study was both to evaluate the effectiveness of this image-guided method in canine patients with spontaneously occurring cancer as well as to illustrate the dog as a well-suited animal model for comparative oncology.Ten dogs with various malignant tumors were included in the study and underwent a whole body FDG PET/CT. One patient has a second PET-CT 5 months after the first study. Patients were diagnosed with histiocytic sarcoma (n = 1, malignant lymphoma (n = 2, mammary carcinoma (n = 4, sertoli cell tumor (n = 1, gastrointestinal stromal tumor (GIST (n = 1 and lung tumor (n = 1. PET/CT data were analyzed with the help of a 5-point scale in consideration of the patients' medical histories.In seven of the ten dogs, the treatment protocol and prognosis were significantly changed due to the results of FDG PET/CT. In the patients with lymphoma (n = 2 tumor extent could be defined on PET/CT because of increased FDG uptake in multiple lymph nodes. This led to the recommendation for a therapeutic polychemotherapy as a treatment. In one of the dogs with mammary carcinoma (n = 4 and in the patient with the lung tumor (n = 1, surgery was cancelled due to the discovery of multiple metastasis. Consequently no treatment was recommended.FDG PET/CT offers additional information in canine patients with malignant disease with a potential improvement of staging and restaging. The encouraging data of this clinical study highlights the possibility to further improve innovative diagnostic and staging methods with regard to comparative oncology. In the future, performing PET/CT not only for staging but also in therapy control could offer a

Single hind limb burn injury to mice alters nuclear factor-κB expression and [¹⁸F] 2-fluoro-2-deoxy-D-glucose uptake.

Science.gov (United States)

Carter, Edward A; Hamrahi, Victoria; Paul, Kasie; Bonab, Ali A; Jung, Walter; Tompkins, Ronald G; Fischman, Alan J

2014-01-01

Burn trauma to the extremities can produce marked systemic effects in mice. Burn injury to the dorsal surface of mice is also associated with changes in glucose metabolism ([18F] 2-fluoro-2-deoxy-D-glucose [18FDG] uptake) by brown adipose tissue (BAT) and nuclear factor (NF)-κB activity in several tissues including skeletal muscle. This study examined the effect of a single hind limb burn in mice on 18FDG uptake by NF-κB activity in vivo, and blood flow was determined by laser Doppler techniques. Male NF-κB luciferase reporter mice (28-30 g) were anesthetized, both legs were shaven, and the right leg was subjected to scald injury by immersion in 90°C water for 5 seconds. Sham-treated animals were used as controls. Each burned and sham mouse was resuscitated with saline (2 mL, i.p.). The individual animals were placed in wire bottom cages with no food and free access to water. After 24 hours, the animals were imaged with laser Doppler for measuring blood flow in the hind limb. The animals were then unanesthetized with 50 μCi of FDG or luciferin (1.0 mg, i.v.) via tail vein. Five minutes after luciferin injection, NF-κB mice were studied by bioluminescence imaging with a charge-coupled device camera. One hour after 18FDG injection, the animals were killed with carbon dioxide overdose, and 18FDG biodistribution was measured. Tissues were also analyzed for NF-κB luciferase activity. The scalding procedure used here produced a full-thickness burn injury to the leg with sharp margins. 18FDG uptake by the burned leg was lower than that in the contralateral limb. Similarly, luciferase activity and blood flow in the burned leg were lower than those in the contralateral leg. 18FDG uptake by BAT and heart increased, whereas that by brain decreased. In conclusion, the present study suggests that burn injury to a single leg decreased FDG uptake by skeletal muscle but increased 18FDG uptake by BAT. The injury to the leg reduced NF-κB expression compared with the

A simplified one-pot synthesis of 9-[(3-[18F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine([18F]FHPG) and 9-(4-[18F]Fluoro-3-hydroxymethylbutyl)guanine ([18F]FHBG) for gene therapy

International Nuclear Information System (INIS)

Shiue, Grace G.; Shiue, Chyng-Yann; Lee, Roland L.; MacDonald, Douglas; Hustinx, Roland; Eck, Stephen L.; Alavi, Abass A.

2001-01-01

9-[(3-[ 18 F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine ([ 18 F]FHPG, 2) has been synthesized by nucleophilic substitution of N 2 -(p-anisyldiphenylmethyl)-9-{[1-(p-anisyldiphenylmethoxy)-3 -toluenesulfonyloxy-2-propoxy]methyl}guanine (1) with potassium [ 18 F]fluoride/Kryptofix 2.2.2 followed by deprotection with 1 N HCl and purification with different methods in variable yields. When both the nucleophilic substitution and deprotection were carried out at 90 deg. C and the product was purified by HPLC (method A), the yield of compound 2 was 5-10% and the synthesis time was 90 min from EOB. However, if both the nucleophilic substitution and deprotection were carried out at 120 deg. C and the product was purified by HPLC, the yield of compound 2 decreased to 2%. When compound 2 was synthesized at 90 deg. C and purified by Silica Sep-Pak (method B), the yield increased to 10-15% and the synthesis time was 60 min from EOB. Similarly, 9-(4-[ 18 F]fluoro-3-hydroxymethylbutyl)guanine ([ 18 F]FHBG, 4) was synthesized with method A and method B in 9% and 10-15% yield, respectively, in a synthesis time of 90 and 60 min, respectively, from EOB. Compound 2 was relatively unstable in acidic medium at 120 deg. C while compound 4 was stable under the same condition. Both compound 2 and compound 4 had low lipid/water partition coefficient (0.126±0.022, n=5 and 0.165±0.023, n=5, respectively). Although it contains non-radioactive ganciclovir (∼5-30 μg) as a chemical by-product, compound 2 synthesized by method B has a similar uptake in 9L glioma cells as that synthesized by method A, and is a potential tracer for imaging herpes simplex virus thymidine kinase gene expression in tumors using PET. Similarly, compound 4 synthesized by method B contains ∼10-25 μg of penciclovir as a chemical by-product. Thus, the simplified one pot synthesis (method B) is a useful method for synthesizing both compound 2 and compound 4 in good yield for routine clinical use, and the method is

Diagnostic value of 18F-FDG PET and 11C-PIB PET on early stage posterior cortical atrophy

Directory of Open Access Journals (Sweden)

Shuai LIU

2015-08-01

Full Text Available Background  Posterior cortical atrophy (PCA is a kind of progressive neurodegenerative disease with cortical visual impairment as the first symptom. Because of rare clinical incidence, early onset age, special clinical symptoms and unobvious MRI abnormality, the definitive diagnosis of PCA is difficult. This study used 18F-fluoro-2-deoxy-D-glucose (18F-FDG PET and 11C-Pittsburgh compound B (11C-PIB PET for PCA patients with unobvious MRI abnormality, so as to discuss the value of PET in the early diagnosis of PCA.  Methods  Five patients diagnosed as PCA in our hospital between April 2012 and March 2015 were enrolled in this study. Cognitive function was measured by Mini-Mental State Examination (MMSE, Montreal Cognitive Assessment (MoCA, Activities of Daily Living (ADL and Clock Drawing Test (CDT. Brain MRI, 18F-FDG PET and 11C-PIB PET were performed to analyze glucose metabolism and perfusion of posterior cortex.  Results Neuropsychological tests revealed that the ability of writing, calculating, visuospatial and executive function of all these patients were impaired. Color vision tests showed abnormal results. MRI showed that the posterior atrophy (PA scores were 0-2 (average 1 on the left side and 0-1 (average 0.80 on the right side. The medial temporal atrophy (MTA scores were 1-3 (average 1.80 on the left side and 1-4 (average 2 on the right side. The ventricular enlargement (VE scores were 1-2 (average 1.80 on the left side and 1-2 (average 1.60 on the right side. 18F-FDG PET showed glucose metabolism decreased obviously on bilateral temporo-parieto-occipital cortex, precuneus and cingulate gyrus, and slightly on frontal lobes and subcortical structure. 11C-PIB PET showed radioactive 11C-PIB deposition on bilateral frontal, temporal, parietal and occipital cortex, and the outline of cerebellar cortex was clear.  Conclusions  For PCA patients whose parietal and occipital cortical atrophy is not obvious on MRI, 18F-FDG PET

18F-fluoro-2-deoxyglucose PET informs neutrophil accumulation and activation in lipopolysaccharide-induced acute lung injury.

Science.gov (United States)

Rodrigues, Rosana S; Bozza, Fernando A; Hanrahan, Christopher J; Wang, Li-Ming; Wu, Qi; Hoffman, John M; Zimmerman, Guy A; Morton, Kathryn A

2017-05-01

Molecular imaging of the earliest events related to the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) could facilitate therapeutic development and patient management. We previously reported that 18 F-fluoro-2-deoxyglucose ( 18 F-FDG) PET identifies ALI/ARDS prior to radiographic abnormalities. The purpose of this study was to establish the time courses of 18 F-FDG uptake, edema and neutrophil recruitment in an endotoxin-induced acute lung injury model and to examine molecular events required for 14 C-2DG uptake in activated neutrophils. Lung uptake of 18 F-FDG was measured by PET in control male Sprague Dawley rats and at 2, 6 and 24h following the intraperitoneal injection of 10mg/kg LPS. Lung edema (attenuation) was measured by microCT. Neutrophil influx into the lungs was measured by myeloperoxidase assay. Control and activated human donor neutrophils were compared for uptake of 14 C-2DG, transcription and content of hexokinase and GLUT isoforms and for hexokinase (HK) activity. Significant uptake of 18 F-FDG occurred by 2h following LPS, and progressively increased to 24h. Lung uptake of 18 F-FDG preceded increased CT attenuation (lung edema). Myeloperoxidase activity in the lungs, supporting neutrophil influx, paralleled 18 F-FDG uptake. Activation of isolated human neutrophils resulted in increased uptake of 14 C-2DG, expression of GLUT 3 and GLUT 4 and expression and increased HK1 activity. Systemic endotoxin-induced ALI results in very early and progressive uptake of 18 F-FDG, parallels neutrophil accumulation and occurs earlier than lung injury edema. Activated neutrophils show increased uptake of 14 C-2DG, expression of specific GLUT3, GLUT4 and HK1 protein and HK activity. ADVANCES IN KNOWLEDGE AND IMPLICATIONS FOR PATIENT CARE: 18 F-FDG pulmonary uptake is an early biomarker of neutrophil recruitment in ALI and is associated with specific molecular events that mediate 14 C-2DG uptake in activated neutrophils. 18 F

Fluorinated glucose analog, 2-fluoro-2-deoxy-D-glucose (F-18): nontoxic tracer for rapid tumor detection

International Nuclear Information System (INIS)

Som, P.; Atkins, H.L.; Bandoypadhyay, D.

1980-01-01

Rapid uptake of F-18 FDG was observed in a variety of transplanted and spontaneous tumors in animals. The tumor uptake reached a peak by 30 min and remained relatively constant up to 60 min, with a very slow wash-out of F-18 activity from the tumor thereafter. Tumor-to-normal tissue and tumor-to-blood ratios ranged from 2.10 to 9.15 and 2.61 to 17.82, respectively, depending on the type of tumor. A scintiscan of a seminoma in a dog showed very high uptake in the viable part and lack of uptake in the necrotic mass. Toxicological studies in mice using 1000 times human tracer dose (HTD) per week for 3 weeks and in dogs using 50 times HTD per week for 3 weeks did not show any evidence of acute or chronic toxicity

Tomography by positrons emission: integral unit to the service of Mexico

International Nuclear Information System (INIS)

Lopez D, F.A.

2005-01-01

The applications of the Positron emission tomography (PET) together with the one radiopharmaceutical 2 - [ 18 F]-fluoro-2-deoxy-D-glucose in the area of the medical imaging is expanding quickly and it possesses a bigger impact at the moment in favor of those patient to who suffers an oncological, cardiac or neurological illness in Mexico. (Author)

Tomography by positrons emission: integral unit to the service of Mexico; Tomografia por emision de positrones: unidad integral al servicio de Mexico

Energy Technology Data Exchange (ETDEWEB)

Lopez D, F A [Unidad PET-Ciclotron, Facultad de Medicina, UNAM (Mexico)

2005-07-01

The applications of the Positron emission tomography (PET) together with the one radiopharmaceutical 2 - [{sup 18} F]-fluoro-2-deoxy-D-glucose in the area of the medical imaging is expanding quickly and it possesses a bigger impact at the moment in favor of those patient to who suffers an oncological, cardiac or neurological illness in Mexico. (Author)

Mutagenicity of γ-irradiated oxygenated and deoxygenated solutions of 2-deoxy-D-ribose and D-ribose in Salmonella typhimurium

International Nuclear Information System (INIS)

Wilmer, J.; Leveling, H.; Schubert, J.

1981-01-01

Solutions of 2-deoxy-D-ribose and D-ribose were γ-irradiated under different experimental conditions and tested for mutagenicity, with and without preincubation, in Salmonella typhimurium. The irradiated sugar solutions were mutagenic in the tester strains TA 100 and TA 98. Except for malonaldehyde (MDA), which is not mutagenic in the concentrations produced radiolytically, the relative mutagenicities of the individual radiolytic products are unknown. With irradiated solutions of 2-deoxy-D-ribose, a relationship was found between the level of non-MDA aldehydes and the mutagenicity in TA 100. Heating the irradiated solutions of 2-deoxy-D-ribose resulted in a temperature-dependent reduction fo the mutagenicity. Autoclaved, non-irradiated solutions of 2-deoxy-D-ribose were not mutagenic in the Salmonella test. (orig.)

Increased fluoro-deoxy-D-glucose uptake on positron emission tomography-computed tomography postbronchoalveolar lavage: a potential cause of radiologic misinterpretation.

LENUS (Irish Health Repository)

Leong, Sum

2011-08-01

Cytologic analysis of bronchoalveolar lavage (BAL) fluid is used for lung cancer diagnosis. We describe a patient with a history of rectal carcinoma who presented with a new lung mass. BAL was performed, with positron emission tomography-computed tomography the following day. There was mildly increased fluoro-deoxy-D-glucose uptake in areas of the lung parenchyma with new ground-glass opacification. This created ambiguity in staging, clarified 2 weeks later by a computed tomography showing complete resolution of the ground-glass opacity. Clinicians should be aware that BAL may cause increased pulmonary fluoro-deoxy-D-glucose uptake, making accurate radiologic interpretation problematic. We suggest that to optimize positron emission tomography-computed tomography, studies should not be performed within 24 hours of BAL.

Optimizing cancer radiotheraphy with 2-deoxy-D-glucose. Dose escalation studies in patients with glioblastoma multiforme

Energy Technology Data Exchange (ETDEWEB)

Singh, D.; Gupta, J.P. [Dharmshila Cancer Hospital, New Delhi (India); Banerji, A.K. [Vidyasagar Inst. of Mental Health and Neurosciences, New Delhi (India); Dwarakanath, B.S.; Tripathi, R.P.; Mathew, T.L.; Ravindranath, T. [Institute of Nuclear Medicine and Allied Sciences, Delhi (India); Jain, V. [Wright State University, Dayton, OH (United States). Kettering Medical Center

2005-08-01

Background and purpose: Higher rates of glucose utilization and glycolysis generally correlate with poor prognosis in several types of malignant tumors. Own earlier studies on model systems demonstrated that the nonmetabolizable glucose analog 2-deoxy-D-glucose (2-DG) could enhance the efficacy of radiotherapy in a dose-dependent manner by selectively sensitizing cancer cells while protecting normal cells. Phase I/II clinical trials indicated that the combination of 2-DG, at an oral dose of 200 mg/kg body weight (BW), with large fractions of {gamma}-radiation was well tolerated in cerebral glioma patients. Since higher 2-DG doses are expected to improve the therapeutic gain, present studies were undertaken to examine the tolerance and safety of escalating 2-DG dose during combined treatment (2-DG + radiotherapy) in glioblastoma multiforme patients. Patients and methods: Untreated patients with histologically proven glioblastoma multiforme (WHO criteria) were included in the study. Seven weekly fractions of {sup 60}C {gamma}-rays (5 Gy/fraction) were delivered to the tumor volume (presurgical CT/MRI evaluation) plus 3 cm margin. Escalating 2-DG doses (200-250-300 mg/kg BW) were administered orally 30 min before irradiation after overnight fasting. Acute toxicity and tolerance were studied by monitoring the vital parameters and side effects. Late radiation damage and treatment responses were studied radiologically and clinically in surviving patients. Results: Transient side effects similar to hypoglycemia were observed in most of the patients. Tolerance and patient compliance to the combined treatment were very good up to a 2-DG dose of 250 mg/kg BW. However, at the higher dose of 300 mg/kg BW, two out of six patients were very restless and could not complete treatment, though significant changes in the vital parameters were not observed even at this dose. No significant damage to the normal brain tissue was observed during follow-up in seven out of ten patients who

Synthesis, characterization and biodistribution of technetium complexes (99Tc/99mTc) with 2-amino-2-deoxy-D-hexose oximes

International Nuclear Information System (INIS)

Steinmetz, H.J.

1993-05-01

In the present work, the synthesis and isolation of isomeric complexes of technetium ( 99 Tc/ 99m Tc) with the 2-amino-2-deoxy-D-hexoses D-glucose aminoxime, D-galactose aminoxime and D-mannose aminoxime, the characterization of the complexes as 99 Tc compounds, and bio-distribution studies on the analogous 99m Tc complexes have been untertaken. As a first step, the free ligands were synthesized and identified using elemental analysis, infra-red and nuclear magnetic resonance spectroscopy and FAB mass spectroscopy. In the bio-distribution studies on the 99m Tc complexes of D-glucose aminoxime and of D-galactose aminoxime in NMRI mice, significant short-term accumulation of 99m Tc activity in heart muscle could be detected, which may be attributed to a biochemical transport mechanism. Uptake in the lungs and the liver was found, but a more significant uptake was observed in the kidneys, where the complexes were rapidly secreted in proportion to their concentration in the blood plasma. (orig./BBR) [de

18F-FDG-PET Correlates of Impulse Control Disorder in a Diabetic Patient.

Science.gov (United States)

Yulug, Burak; Hanoglu, Lütfü; Tavlı, Ahmet Mithat; Cakir, Tansel; Khanmammadov, Elmir; Olmuscelik, Oktay

2016-01-01

Studies have already shown that hyperglycemia and insulin resistance are significantly associated with the impairment of cerebral glucose metabolism that may secondary lead to cognitive disturbances. In this study, we aimed to evaluate the neurometabolic correlates of diabetes in a patient with Intermittent explosive disorder (IED). We have investigated the cerebral glucose metabolism via 2-[18F]-fluoro-2- deoxy-D-glucose positron emission tomography (FDG-PET) in a diabetic patient with aggressive outbursts. We have found significantly reduced glucose uptake in left temporoparietal region, pontin area, and left nucleus lentiformis. Our present results indicate decreased cerebral glucose metabolism in specific cerebral cortical and subcortical areas. The main limitation of this report is that, this is a single case study and that these findings need to be replicated in well- conducted randomized controlled studies by using additional neuroquantitative methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Clinical impact of FDG-PET/CT in the planning of radiotherapy for early-stage Hodgkin lymphoma

DEFF Research Database (Denmark)

Hutchings, Martin; Loft, Annika; Hansen, Mads

2007-01-01

BACKGROUND: Early-stage Hodgkin lymphoma (HL) has excellent survival rates but carries a high risk of late treatment-related adverse effects. Modern, individualised therapeutic strategies require an accurate determination of the extent of the disease. This study investigated the potential impact...... of 2-[18F]-fluoro-2-deoxy-d-glucose positron emission tomography/computerised tomogrpahy (FDG-PET/CT) in the planning of involved field radiotherapy (IFRT). PATIENTS AND METHODS: Thirty patients received staging FDG-PET/CT before therapy, and IFRT after a short course of ABVD (adriamycin, bleomycin......, vinblastine, dacarbazine) chemotherapy. IFRT planning was performed using only the CT data from the FDG-PET/CT scan. Later, the IFRT planning was performed anew using the FDG-PET/CT data as basis for contouring. RESULTS: In 20 out of 30 patients, the radiotherapy (RT) course was unaffected by the addition...

Enhancement in the antitumor immunity contributes to the radio-sensitization of tumors by 2-deoxy-D-glucose

International Nuclear Information System (INIS)

Farooque, Abdullah; Dwarakanath, B.S.

2014-01-01

The glycolytic inhibitor, 2-deoxy-D-glucose sensitizes tumor cells while protects normal cells to radiation and chemotherapeutics in vitro and in vivo. Further, 2-DG has also been suggested as an adjuvant for low dose radiation therapy. Since immunomodulation plays an important role in tumor responses to anticancer therapies and glycolysis influences the activation of lymphocytes, we investigated the effects of 2-DG on immuno-regulatory networks during radiosensitization of Ehrlich ascites tumor (EAT) in mice. Mice were treated with 10 Gy of focal irradiation to tumor and single dose of 2-DG (2 gm/Kg/b.wt) intravenously. Immuno-phenotyping was done using flow cytometry, while cytokines and antibody classes were analyzed using bead array and ELISA. Further, mRNA and protein levels of transcription factors were assessed in sorted splenic CD4 + cells using real time PCR and Western blot techniques. Immune activation in the form of increase in the expression of NK cells, dendritic cells, macrophages and CD4 + cells, while a decrease was noted in myeloid derived suppressor cells (MDSCs), B cells, tumor tolerant CD4 + PD1 + and CD8 + PD1 + after the combined treatment (2-DG+ Radiation). Interestingly, decrease in the (CD4 + CD62L + ) naive cells with concomitant increase in effector memory cells (CD4 + CD44 + ) indicated the immune activation and memory response. This activation was found to be dependent on the restoration of TCR and CD28 mediated signaling leading to the shift from Th2 and Th17 to Th1 in the form of cytokine and antibody class switching and decrease in inflammation, which was correlated with the modulation of transcriptional factors in splenic CD4 + cells. Interestingly, depletion of T-regulatory cells appears to be partly responsible for the immune activation observed. These studies for the first time revealed the immuno-modulatory potential of 2-DG that should facilitate the optimization of protocols for enhancing the efficacy of radiotherapy, besides

Proportion of false-positive lesions at interim and end-of-treatment FDG-PET in lymphoma as determined by histology: Systematic review and meta-analysis

Energy Technology Data Exchange (ETDEWEB)

Adams, Hugo J.A., E-mail: h.j.a.adams@gmail.com; Kwee, Thomas C.

2016-11-15

Purpose: To systematically review and meta-analyze the proportion of false-positive lesions at interim and end-of-treatment {sup 18}F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) in lymphoma using biopsy as reference standard. Materials and methods: Medline was searched for original studies. Methodological quality of included studies was evaluated, and results were meta-analytically summarized using random effects (in case of interstudy heterogeneity [I{sup 2} ≤ 50%]) or fixed effects (in case of no interstudy heterogeneity [I{sup 2} > 50%]). Results: Eleven studies, comprising 139 patients who underwent biopsy of an FDG-avid lesion during or after completion of antilymphoma treatment, were included. Overall methodological quality was moderate. The proportion of false-positive results among all biopsied FDG-avid lesions at PET performed during of after completion of treatment ranged between 7.7% and 90.5% (the vast majority was due to inflammatory changes), with a weighted summary proportion (random effects, I{sup 2} = 75.7%) of 55.7% (95% confidence interval [CI]: 32.6–76.6%). There were no available studies on interim FDG-PET in Hodgkin lymphoma. The pooled summary false-positive proportions were 83.0% (95% CI: 72.0%–90.2%) for interim FDG-PET in non-Hodgkin lymphoma (fixed effects, I{sup 2} = 27.7%), 23.1% (95% CI: 4.7%–64.5%) for end-of-treatment FDG-PET in Hodgkin lymphoma (random effects; I{sup 2} = 67.1%), and 31.5% (95% CI: 3.9%–83.9%) for end-of-treatment FDG-PET in non-Hodgkin lymphoma (random effects, I{sup 2} = 68.3%). Conclusion: Both interim and end-of-treatment FDG-PET scans in patients with lymphoma suffer from a very high number of false-positive FDG-avid lesions. This finding, in combination with the previously reported high number of false-negative FGD-PET scans for residual disease detection, suggests that the role of interim and end-of-treatment FDG-PET should be reconsidered.

Evaluation of F-18-labeled 5-iodocytidine ({sup 18}F-FIAC) as a new potential positron emission tomography probe for herpes simplex virus type 1 thymidine kinase imaging

Energy Technology Data Exchange (ETDEWEB)

Chan, Pei-Chia; Wu, Chun-Yi; Chang, Wen-Yi; Chang, Wei-Ting [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 11221, Taiwan (China); Alauddin, Mian [Department of Experimental Diagnostic Imaging, MD Anderson Cancer Center, University of Texas, TX, 77054 (United States); Liu, Ren-Shan [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 11221, Taiwan (China); Department of Nuclear Medicine, Faculty of Medicine, National Yang-Ming University, Taipei, 11221, Taiwan (China); Department of Nuclear Medicine and National PET/Cyclotron Center, Taipei Veterans General Hospital, Taipei, 11217, Taiwan (China); Lin, Wuu-Jyh [Institute of Nuclear Energy Research, Atomic Energy Council, Taoyuan, 32546, Taiwan (China); Chen, Fu-Du [College of Health and Leisure Science, TransWorld University, Yunlin, 64063, Taiwan (China); Chen, Chuan-Lin, E-mail: clchen2@ym.edu.tw [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 11221, Taiwan (China); Wang, Hsin-Ell, E-mail: hewang@ym.edu.tw [Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, 11221, Taiwan (China)

2011-10-15

Objective: Herpes simplex virus type 1 thymidine kinase (HSV1-tk) gene in combination with radiolabeled nucleoside substrates is the most widely used reporter system. This study characterized 1-(2'-deoxy-2'-[{sup 18}F]fluoro-{beta}-D-arabinofuranosyl)-5-iodocytosine ({sup 18}F-FIAC) as a new potential positron emission tomography (PET) probe for HSV1-tk gene imaging and compared it with 2'-deoxy-2'-[{sup 18}F]fluoro-5-iodo-1-{beta}-D-arabinofuranosyluracil ({sup 18}F-FIAU) and 2'-deoxy-2'-[{sup 18}F]fluoro-5-ethyl-1-{beta}-D-arabinofuranosyluracil({sup 18}F-FEAU) (thymidine analogues) in an NG4TL4-WT/STK sarcoma-bearing mouse model. Methods: A cellular uptake assay, biodistribution study, radioactive metabolites assay and microPET imaging of NG4TL4-WT/STK tumor-bearing mice post administration of {sup 18}F-FIAC, {sup 18}F-FIAU and {sup 18}F-FEAU were conducted to characterize the biological properties of these tracers. Results: Highly specific uptake of {sup 18}F-FIAC, {sup 18}F-FIAU and {sup 18}F-FEAU in tk-transfected [tk(+)] cells was observed. The tk(+)-to-tk(-) cellular uptake ratio after a 2-h incubation was 66.6{+-}25.1, 76.3{+-}18.2 and 247.2{+-}37.2, respectively. In biodistribution studies, {sup 18}F-FIAC showed significant tk(+) tumor specificity (12.6; expressed as the tk(+)-to-tk(-) tumor uptake ratio at 2 h postinjection) comparable with {sup 18}F-FIAU (15.8) but lower than {sup 18}F-FEAU (48.0). The results of microPET imaging also revealed the highly specific accumulation of these three radioprobes in the NG4TL4-tk(+) tumor. Conclusion: Our findings suggested that the cytidine analogue {sup 18}F-FIAC is a new potential PET probe for the imaging of HSV1-tk gene expression. {sup 18}F-FIAC may be regarded as the prodrug of {sup 18}F-FIAU in vivo.

Defective glycolysis and the use of 2-deoxy-D-glucose in polycystic kidney disease: from animal models to humans.

Science.gov (United States)

Magistroni, Riccardo; Boletta, Alessandra

2017-08-01

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited renal disease characterized by bilateral renal cyst formation. ADPKD is one of the most common rare disorders, accounting for ~10% of all patients with end-stage renal disease (ESRD). ADPKD is a chronic disorder in which the gradual expansion of cysts that form in a minority of nephrons eventually causes loss of renal function due to the compression and degeneration of the surrounding normal parenchyma. Numerous deranged pathways have been identified in the cyst-lining epithelia, prompting the design of potential therapies. Several of these potential treatments have proved effective in slowing down disease progression in pre-clinical animal studies, while only one has subsequently been proven to effectively slow down disease progression in patients, and it has recently been approved for therapy in Europe, Canada and Japan. Among the affected cellular functions and pathways, recent investigations have described metabolic derangement in ADPKD as a major trait offering additional opportunities for targeted therapies. In particular, increased aerobic glycolysis (the Warburg effect) has been described as a prominent feature of ADPKD kidneys and its inhibition using the glucose analogue 2-deoxy-D-glucose (2DG) proved effective in slowing down disease progression in preclinical models of the disease. At the same time, previous clinical experiences have been reported with 2DG, showing that this compound is well tolerated in humans with minimal and reversible side effects. In this work, we review the literature and speculate that 2DG could be a good candidate for a clinical trial in humans affected by ADPKD.

Incidental head and neck findings on 18F-fluoro-deoxy-glucose positron emission tomography computed tomography.

Science.gov (United States)

Williams, S P; Kinshuck, A J; Williams, C; Dwivedi, R; Wieshmann, H; Jones, T M

2015-09-01

The overlapping risk factors for lung and head and neck cancer present a definite risk of synchronous malignant pathology. This is the first study to specifically review incidental positron emission tomography computed tomography findings in the head and neck region in lung carcinoma patients. A retrospective review was performed of all lung cancer patients who underwent positron emission tomography computed tomography imaging over a five-year period (January 2008 - December 2012), identified from the Liverpool thoracic multidisciplinary team database. Six hundred and nine patients underwent positron emission tomography computed tomography imaging over this period. In 76 (12.5 per cent) scans, incidental regions of avid 18F-fluoro-deoxy-glucose uptake were reported in the head and neck region. In the 28 patients who were fully investigated, there were 4 incidental findings of malignancy. In lung cancer patients undergoing investigative positron emission tomography computed tomography scanning, a significant number will also present with areas of clinically significant 18F-fluoro-deoxy-glucose uptake in the head and neck region. Of these, at least 5 per cent may have an undiagnosed malignancy.

A simplified one-pot synthesis of 9-[(3-[{sup 18}F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine([{sup 18}F]FHPG) and 9-(4-[{sup 18}F]Fluoro-3-hydroxymethylbutyl)guanine ([{sup 18}F]FHBG) for gene therapy

Energy Technology Data Exchange (ETDEWEB)

Shiue, Grace G.; Shiue, Chyng-Yann E-mail: Shiue@rad.upenn.edu; Lee, Roland L.; MacDonald, Douglas; Hustinx, Roland; Eck, Stephen L.; Alavi, Abass A

2001-10-01

9-[(3-[{sup 18}F]Fluoro-1-hydroxy-2-propoxy)methyl]guanine ([{sup 18}F]FHPG, 2) has been synthesized by nucleophilic substitution of N{sup 2}-(p-anisyldiphenylmethyl)-9-{l_brace}[1-(p-anisyldiphenylmethoxy)-3 -toluenesulfonyloxy-2-propoxy]methyl{r_brace}guanine (1) with potassium [{sup 18}F]fluoride/Kryptofix 2.2.2 followed by deprotection with 1 N HCl and purification with different methods in variable yields. When both the nucleophilic substitution and deprotection were carried out at 90 deg. C and the product was purified by HPLC (method A), the yield of compound 2 was 5-10% and the synthesis time was 90 min from EOB. However, if both the nucleophilic substitution and deprotection were carried out at 120 deg. C and the product was purified by HPLC, the yield of compound 2 decreased to 2%. When compound 2 was synthesized at 90 deg. C and purified by Silica Sep-Pak (method B), the yield increased to 10-15% and the synthesis time was 60 min from EOB. Similarly, 9-(4-[{sup 18}F]fluoro-3-hydroxymethylbutyl)guanine ([{sup 18}F]FHBG, 4) was synthesized with method A and method B in 9% and 10-15% yield, respectively, in a synthesis time of 90 and 60 min, respectively, from EOB. Compound 2 was relatively unstable in acidic medium at 120 deg. C while compound 4 was stable under the same condition. Both compound 2 and compound 4 had low lipid/water partition coefficient (0.126{+-}0.022, n=5 and 0.165{+-}0.023, n=5, respectively). Although it contains non-radioactive ganciclovir ({approx}5-30 {mu}g) as a chemical by-product, compound 2 synthesized by method B has a similar uptake in 9L glioma cells as that synthesized by method A, and is a potential tracer for imaging herpes simplex virus thymidine kinase gene expression in tumors using PET. Similarly, compound 4 synthesized by method B contains {approx}10-25 {mu}g of penciclovir as a chemical by-product. Thus, the simplified one pot synthesis (method B) is a useful method for synthesizing both compound 2 and compound 4 in

Prebiotic synthesis of 2-deoxy-d-ribose from interstellar building blocks promoted by amino esters or amino nitriles.

Science.gov (United States)

Steer, Andrew M; Bia, Nicolas; Smith, David K; Clarke, Paul A

2017-09-25

Understanding the prebiotic genesis of 2-deoxy-d-ribose, which forms the backbone of DNA, is of crucial importance to unravelling the origins of life, yet remains open to debate. Here we demonstrate that 20 mol% of proteinogenic amino esters promote the selective formation of 2-deoxy-d-ribose over 2-deoxy-d-threopentose in combined yields of ≥4%. We also demonstrate the first aldol reaction promoted by prebiotically-relevant proteinogenic amino nitriles (20 mol%) for the enantioselective synthesis of d-glyceraldehyde with 6% ee, and its subsequent conversion into 2-deoxy-d-ribose in yields of ≥ 5%. Finally, we explore the combination of these two steps in a one-pot process using 20 mol% of an amino ester or amino nitrile promoter. It is hence demonstrated that three interstellar starting materials, when mixed together with an appropriate promoter, can directly lead to the formation of a mixture of higher carbohydrates, including 2-deoxy-d-ribose.

18F-fluoro-2-deoxyglucose PET informs neutrophil accumulation and activation in lipopolysaccharide-induced acute lung injury genetic algorithm

International Nuclear Information System (INIS)

Rodrigues, Rosana S.; Bozza, Fernando A.; Hanrahan, Christopher J.; Wang, Li-Ming; Wu, Qi; Hoffman, John M.; Zimmerman, Guy A.; Morton, Kathryn A.

2017-01-01

Introduction: Molecular imaging of the earliest events related to the development of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) could facilitate therapeutic development and patient management. We previously reported that 18 F-fluoro-2-deoxyglucose ( 18 F-FDG) PET identifies ALI/ARDS prior to radiographic abnormalities. The purpose of this study was to establish the time courses of 18 F-FDG uptake, edema and neutrophil recruitment in an endotoxin-induced acute lung injury model and to examine molecular events required for 14 C-2DG uptake in activated neutrophils. Methods: Lung uptake of 18 F-FDG was measured by PET in control male Sprague Dawley rats and at 2, 6 and 24 h following the intraperitoneal injection of 10 mg/kg LPS. Lung edema (attenuation) was measured by microCT. Neutrophil influx into the lungs was measured by myeloperoxidase assay. Control and activated human donor neutrophils were compared for uptake of 14 C-2DG, transcription and content of hexokinase and GLUT isoforms and for hexokinase (HK) activity. Results: Significant uptake of 18 F-FDG occurred by 2 h following LPS, and progressively increased to 24 h. Lung uptake of 18 F-FDG preceded increased CT attenuation (lung edema). Myeloperoxidase activity in the lungs, supporting neutrophil influx, paralleled 18 F-FDG uptake. Activation of isolated human neutrophils resulted in increased uptake of 14 C-2DG, expression of GLUT 3 and GLUT 4 and expression and increased HK1 activity. Conclusion: Systemic endotoxin-induced ALI results in very early and progressive uptake of 18 F-FDG, parallels neutrophil accumulation and occurs earlier than lung injury edema. Activated neutrophils show increased uptake of 14 C-2DG, expression of specific GLUT3, GLUT4 and HK1 protein and HK activity. Advances in knowledge and implications for patient care: 18 F-FDG pulmonary uptake is an early biomarker of neutrophil recruitment in ALI and is associated with specific molecular events that mediate 14

Regional metabolic liver function measured in patients with cirrhosis by 2-[¹⁸F]fluoro-2-deoxy-D-galactose PET/CT.

Science.gov (United States)

Sørensen, Michael; Mikkelsen, Kasper S; Frisch, Kim; Villadsen, Gerda E; Keiding, Susanne

2013-06-01

There is a clinical need for methods that can quantify regional hepatic function non-invasively in patients with cirrhosis. Here we validate the use of 2-[(18)F]fluoro-2-deoxy-d-galactose (FDGal) PET/CT for measuring regional metabolic function to this purpose, and apply the method to test the hypothesis of increased intrahepatic metabolic heterogeneity in cirrhosis. Nine cirrhotic patients underwent dynamic liver FDGal PET/CT with blood samples from a radial artery and a liver vein. Hepatic blood flow was measured by indocyanine green infusion/Fick's principle. From blood measurements, hepatic systemic clearance (Ksyst, Lblood/min) and hepatic intrinsic clearance (Vmax/Km, Lblood/min) of FDGal were calculated. From PET data, hepatic systemic clearance of FDGal in liver parenchyma (Kmet, mL blood/mL liver tissue/min) was calculated. Intrahepatic metabolic heterogeneity was evaluated in terms of coefficient-of-variation (CoV, %) using parametric images of Kmet. Mean approximation of Ksyst to Vmax/Km was 86% which validates the use of FDGal as PET tracer of hepatic metabolic function. Mean Kmet was 0.157 mL blood/mL liver tissue/min, which was lower than 0.274 mL blood/mL liver tissue/min, previously found in healthy subjects (pdynamic FDGal PET/CT with arterial sampling provides an accurate measure of regional hepatic metabolic function in patients with cirrhosis. This is likely to have clinical implications for the assessment of patients with liver disease as well as treatment planning and monitoring. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

A convenient route to N-acetyl-D-glucosamine-2-C-d and N-acetyl-D-mannosamine-2-C-d

International Nuclear Information System (INIS)

Szilagyi, L.; Bujtas, G.

1977-01-01

Title compounds were prepared through epimerisation of 2-acetamido-2-deoxy-D-glucose in NaOD. The isotopic purity of the products was determined by NMR and mass spectroscopy. The mechanism of epimerisation is briefly discussed. (orig.) [de

Combined Modality Treatment for PET-Positive Non-Hodgkin Lymphoma: Favorable Outcomes of Combined Modality Treatment for Patients With Non-Hodgkin Lymphoma and Positive Interim or Postchemotherapy FDG-PET

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Halasz, Lia M. [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Jacene, Heather A. [Department of Imaging, Dana-Farber Cancer Institute, and Department of Radiology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Catalano, Paul J. [Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Van den Abbeele, Annick D. [Department of Imaging, Dana-Farber Cancer Institute, and Department of Radiology, Brigham and Women' s Hospital, Boston, Massachusetts (United States); LaCasce, Ann [Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts (United States); Mauch, Peter M. [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Boston, Massachusetts (United States); Ng, Andrea K., E-mail: ang@lroc.harvard.edu [Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham and Women' s Hospital, Boston, Massachusetts (United States)

2012-08-01

Purpose: To evaluate outcomes of patients treated for aggressive non-Hodgkin lymphoma (NHL) with combined modality therapy based on [{sup 18}F]fluoro-2-deoxy-2-D-glucose positron emission tomography (FDG-PET) response. Methods and Materials: We studied 59 patients with aggressive NHL, who received chemotherapy and radiation therapy (RT) from 2001 to 2008. Among them, 83% of patients had stage I/II disease. Patients with B-cell lymphoma received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone)-based chemotherapy, and 1 patient with anaplastic lymphoma kinase-negative anaplastic T-cell lymphoma received CHOP therapy. Interim and postchemotherapy FDG-PET or FDG-PET/computed tomography (CT) scans were performed for restaging. All patients received consolidated involved-field RT. Median RT dose was 36 Gy (range, 28.8-50 Gy). Progression-free survival (PFS) and local control (LC) rates were calculated with and without a negative interim or postchemotherapy FDG-PET scan. Results: Median follow-up was 46.5 months. Thirty-nine patients had negative FDG-PET results by the end of chemotherapy, including 12 patients who had a negative interim FDG-PET scan and no postchemotherapy PET. Twenty patients were FDG-PET-positive, including 7 patients with positive interim FDG-PET and no postchemotherapy FDG-PET scans. The 3-year actuarial PFS rates for patients with negative versus positive FDG-PET scans were 97% and 90%, respectively. The 3-year actuarial LC rates for patients with negative versus positive FDG-PET scans were 100% and 90%, respectively. Conclusions: Patients who had a positive interim or postchemotherapy FDG-PET had a PFS rate of 90% at 3 years after combined modality treatment, suggesting that a large proportion of these patients can be cured with consolidated RT.

Modulatory action of 2-deoxy-D-glucose on mitomycin C-and 4-nitroquinoline-1-oxide-induced genotoxicity in Swiss albino mice In vivo

Directory of Open Access Journals (Sweden)

Mohapatra Rashmi

2009-09-01

Full Text Available Background: 2-Deoxy-D-glucose (2-DG, a structural analog of glucose is an effective inhibitor of glucose metabolism and ATP production. It selectively accumulates in cancer cells and interferes with glycolysis leading to cell death. 2-DG is shown to differentially enhance the radiation-induced damage in cancer cells both under euoxic and hypoxic conditions. A combination of 2-DG and ionizing radiation selectively destroys tumors while protecting the normal tissue. 2-DG is being advocated as an adjuvant in the radiotherapy and chemotherapy of cancer. Objective: The present investigation focuses on the modulatory effect of 2-DG on mitomycin C- (MMC and 4-nitroquinoline-1-oxide (4-NQO-induced cytogenetic damage in bone marrow cells of Swiss albino mice in vivo. Materials and Methods: Experimental animals were pretreated with 2-DG (500 mg/kg, i.p. for five consecutive days followed by MMC (2 mg/kg, i.p or 4-NQO (15 mg/kg, i.p., 24h prior to sacrifice. Control animals were given either the mixture of olive oil and acetone (3:1 or distilled water. Bone marrow cells were processed for the micronucleus assay and metaphase analysis for estimating cytogenetic damage. Results: 2-DG significantly (P < 0.001 reduced the frequency of aberrant cells induced by MMC (~90% and 4-NQO (~74%. Incidence of micronucleated polychromatic erythrocytes (MnPCEs induced by the mutagens were reduced up to 68%. Conclusion: 2-DG effectively reduces the MMC-and 4-NQO-induced genotoxicity.

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)

Molecular basis for the regulation of hypoxia-inducible factor-1α levels by 2-deoxy-D-ribose.

Science.gov (United States)

Ikeda, Ryuji; Tabata, Sho; Tajitsu, Yusuke; Nishizawa, Yukihiko; Minami, Kentaro; Furukawa, Tatsuhiko; Yamamoto, Masatatsu; Shinsato, Yoshinari; Akiyama, Shin-Ichi; Yamada, Katsushi; Takeda, Yasuo

2013-09-01

The angiogenic factor, platelet-derived endothelial cell growth factor/thymidine phosphorylase (PD-ECGF/TP), stimulates the chemotaxis of endothelial cells and confers resistance to apoptosis induced by hypoxia. 2-Deoxy-D-ribose, a degradation product of thymidine generated by TP enzymatic activity, inhibits the upregulation of hypoxia-inducible factor (HIF) 1α, BNIP3 and caspase-3 induced by hypoxia. In the present study, we investigated the molecular basis for the suppressive effect of 2-deoxy-D-ribose on the upregulation of HIF-1α. 2-Deoxy-D-ribose enhanced the interaction of HIF-1α and the von Hippel-Lindau (VHL) protein under hypoxic conditions. It did not affect the expression of HIF-1α, prolyl hydroxylase (PHD)1/2/3 and VHL mRNA under normoxic or hypoxic conditions, but enhanced the interaction of HIF-1α and PHD2 under hypoxic conditions. 2-Deoxy-D-ribose also increased the amount of hydroxy-HIF-1α in the presence of the proteasome inhibitor MG-132. The expression levels of TP are elevated in many types of malignant solid tumors and, thus, 2-deoxy-D-ribose generated by TP in these tumors may play an important role in tumor progression by preventing hypoxia-induced apoptosis.

Heterogeneity in 2-deoxy-D-glucose-induced modifications in energetics and radiation responses of human tumor cell lines

International Nuclear Information System (INIS)

Dwarkanath, Bilikere S.; Zolzer, Frido; Chandana, Sudhir; Bauch, Thomas; Adhikari, Jawahar S.; Muller, Wolfgang U.; Streffer, Christian; Jain, Viney

2001-01-01

Purpose: The glucose analog and glycolytic inhibitor, 2-deoxy-D-glucose (2-DG), has been shown to differentially enhance the radiation damage in tumor cells by inhibiting the postirradiation repair processes. The present study was undertaken to examine the relationship between 2-DG-induced modification of energy metabolism and cellular radioresponses and to identify the most relevant parameter(s) for predicting the tumor response to the combined treatment of radiation + 2-DG. Methods and Materials: Six human tumor cell lines (glioma: BMG-1 and U-87, squamous cell carcinoma: 4451 and 4197, and melanoma: MeWo and Be-11) were investigated. Cells were exposed to 2 Gy of Co-60 γ-rays or 250 kVP X-rays and maintained under liquid-holding conditions 2-4 h to facilitate repair. 2-DG (5 mM, equimolar with glucose) that was added at the time of irradiation was present during the liquid holding. Glucose utilization, lactate production (enzymatic assays), and adenine nucleotides (high performance liquid chromatography and capillary isotachophoresis) were investigated as parameters of energy metabolism. Induction and repair of DNA damage (comet assay), cytogenetic damage (micronuclei formation), and cell death (macrocolony assay) were analyzed as parameters of radiation response. Results: The glucose consumption and lactate production of glioma cell lines (BMG-1 and U-87) were nearly 2-fold higher than the squamous carcinoma cell lines (4197 and 4451). The ATP content varied from 3.0 to 6.5 femto moles/cell among these lines, whereas the energy charge (0.86-0.90) did not show much variation. Presence of 2-DG inhibited the rate of glucose usage and glycolysis by 30-40% in glioma cell lines and by 15-20% in squamous carcinoma lines, while ATP levels reduced by nearly 40% in all the four cell lines. ATP:ADP ratios decreased to a greater extent (∼40%) in glioma cells than in squamous carcinoma 4451 and MeWo cells; in contrast, presence of 2-DG reduced ADP:AMP ratios by 3-fold in

18F-FDG positron emission tomography/computed tomography in infective endocarditis.

Science.gov (United States)

Salomäki, Soile Pauliina; Saraste, Antti; Kemppainen, Jukka; Bax, Jeroen J; Knuuti, Juhani; Nuutila, Pirjo; Seppänen, Marko; Roivainen, Anne; Airaksinen, Juhani; Pirilä, Laura; Oksi, Jarmo; Hohenthal, Ulla

2017-02-01

The diagnosis of infective endocarditis (IE), especially the diagnosis of prosthetic valve endocarditis (PVE) is challenging since echocardiographic findings are often scarce in the early phase of the disease. We studied the use of 2-[ 18 F]fluoro-2-deoxy-D-glucose ( 18 F-FDG) positron emission tomography/computed tomography (PET/CT) in IE. Sixteen patients with suspected PVE and 7 patients with NVE underwent visual evaluation of 18 F-FDG-PET/CT. 18 F-FDG uptake was measured also semiquantitatively as maximum standardized uptake value (SUV max ) and target-to-background ratio (TBR). The modified Duke criteria were used as a reference. There was strong, focal 18 F-FDG uptake in the area of the affected valve in all 6 cases of definite PVE, in 3 of 5 possible PVE cases, and in 2 of 5 rejected cases. In all patients with definite PVE, SUV max of the affected valve was higher than 4 and TBR higher than 1.8. In contrast to PVE, only 1 of 7 patients with NVE had uptake of 18 F-FDG by PET/CT in the valve area. Embolic infectious foci were detected in 58% of the patients with definite IE. 18 F-FDG-PET/CT appears to be a sensitive method for the detection of paravalvular infection associated with PVE. Instead, the sensitivity of PET/CT is limited in NVE.

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

International Nuclear Information System (INIS)

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

2007-01-01

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

Enhancement of Temozolomide and radiation induced damage in malignant glioma cell lines by 2-deoxy-D-glucose

International Nuclear Information System (INIS)

Kumari, Kalyani; Shyam, Sai; Chandrasekhar Sagar, B.K.; Jagath Lal, G.; Kalia, Vijay Kumar

2014-01-01

Malignant Gliomas are the most common and aggressive CNS tumors. The current standard treatment includes surgery, followed by Temozolomide (TMZ)-Radiotherapy. It leads to increased survival as compared to radiotherapy alone. However hematological toxicities are also increased by the combination treatments. Therefore, it is important to carry out further preclinical studies, to develop more effective treatment for these tumors. 2-deoxy-D-Glucose (2-DG), an inhibitor of glycolytic energy metabolism, has been shown earlier to differentially inhibit growth and survival of tumor cells in vitro. It also increases tumor regression in experimental models; and has been used in a few clinical studies as radiosensitizer. In the present study, effects of combining 2-DG with TMZ on radiation induced damage were studied in established malignant glioma cell lines (U251MG and U87MG); and primary cultures derived from malignant glioma biopsies. Exponentially growing cells were exposed to drugs and radiation. Drugs were removed 4 hours later and cultures were processed further for different assays of damage. Effects on proliferation response, viability and total cellular damage (TCD; micronuclei + apoptosis) were studied after post-treatment growth for 1, 2, 4 or 6 days. Our results showed that combination of 2-DG with TMZ ± Radiation significantly inhibited tumor cell proliferation up to 6 days, at low drug concentrations in primary as well as in established cell lines. The TCD at 24 and 48 hours after Gamma irradiation was also significantly increased by the combination of drugs as compared to individual treatments. Experiments to study proliferation kinetics by flow cytometry and cell survival are in progress. These studies suggest that 2-DG significantly enhances the cytotoxic effect of TMZ + radiation without increasing toxic side effects. Therefore, combining 2-DG with TMZ+ radiation therapy could be a potential strategy to improve the therapeutic outcome for Malignant

2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-D-pyranoside confers neuroprotection in cell and animal models of ischemic stroke through calpain1/PKA/CREB-mediated induction of neuronal glucose transporter 3

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Yu, Shu; Cheng, Qiong; Li, Lu; Liu, Mei; Yang, Yumin; Ding, Fei, E-mail: dingfei@ntu.edu.cn

2014-06-15

Salidroside is proven to be a neuroprotective agent of natural origin, and its analog, 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-D-pyranoside (named SalA-4 g), has been synthesized in our lab. In this study, we showed that SalA-4 g promoted neuronal survival and inhibited neuronal apoptosis in primary hippocampal neurons exposed to oxygen and glucose deprivation (OGD) and in rats subjected to ischemia by transient middle cerebral artery occlusion (MCAO), respectively, and that SalA-4 g was more neuroprotective than salidroside. We further found that SalA-4 g elevated glucose uptake in OGD-injured primary hippocampal neurons and increased the expression and recruitment of glucose transporter 3 (GLUT3) in ischemic brain. Signaling analysis revealed that SalA-4 g triggered the phosphorylation of CREB, and increased the expression of PKA RII in primary hippocampal neurons exposed to OGD injury, while inhibition of PKA/CREB by H-89 alleviated the elevation in glucose uptake and GLUT3 expression, and blocked the protective effects of SalA-4 g. Moreover, SalA-4 g was noted to inhibit intracellular Ca{sup 2+} influx and calpain1 activation in OGD-injured primary hippocampal neurons. Our results suggest that SalA-4 g neuroprotection might be mediated by increased glucose uptake and elevated GLUT3 expression through calpain1/PKA/CREB pathway. - Highlights: • A salidroside (Sal) analog (SalA-4 g) is prepared to be more neuroprotective than Sal. • SalA-4 g protected hippocampal neurons from oxygen and glucose deprivation insult. • SalA-4 g reduced ischemic injury after transient middle cerebral artery occlusion in rats. • Neuroprotection of SalA-4 g was mediated by GLUT3 level via calpain/PKA/CREB pathway.

2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-D-pyranoside confers neuroprotection in cell and animal models of ischemic stroke through calpain1/PKA/CREB-mediated induction of neuronal glucose transporter 3

International Nuclear Information System (INIS)

Yu, Shu; Cheng, Qiong; Li, Lu; Liu, Mei; Yang, Yumin; Ding, Fei

2014-01-01

Salidroside is proven to be a neuroprotective agent of natural origin, and its analog, 2-(4-Methoxyphenyl)ethyl-2-acetamido-2-deoxy-β-D-pyranoside (named SalA-4 g), has been synthesized in our lab. In this study, we showed that SalA-4 g promoted neuronal survival and inhibited neuronal apoptosis in primary hippocampal neurons exposed to oxygen and glucose deprivation (OGD) and in rats subjected to ischemia by transient middle cerebral artery occlusion (MCAO), respectively, and that SalA-4 g was more neuroprotective than salidroside. We further found that SalA-4 g elevated glucose uptake in OGD-injured primary hippocampal neurons and increased the expression and recruitment of glucose transporter 3 (GLUT3) in ischemic brain. Signaling analysis revealed that SalA-4 g triggered the phosphorylation of CREB, and increased the expression of PKA RII in primary hippocampal neurons exposed to OGD injury, while inhibition of PKA/CREB by H-89 alleviated the elevation in glucose uptake and GLUT3 expression, and blocked the protective effects of SalA-4 g. Moreover, SalA-4 g was noted to inhibit intracellular Ca 2+ influx and calpain1 activation in OGD-injured primary hippocampal neurons. Our results suggest that SalA-4 g neuroprotection might be mediated by increased glucose uptake and elevated GLUT3 expression through calpain1/PKA/CREB pathway. - Highlights: • A salidroside (Sal) analog (SalA-4 g) is prepared to be more neuroprotective than Sal. • SalA-4 g protected hippocampal neurons from oxygen and glucose deprivation insult. • SalA-4 g reduced ischemic injury after transient middle cerebral artery occlusion in rats. • Neuroprotection of SalA-4 g was mediated by GLUT3 level via calpain/PKA/CREB pathway

Enriched Water-H2 18O Purification to be Used in Routine 18FDG Production

International Nuclear Information System (INIS)

Al Rayyes, A.H.

2009-01-01

Oxygen-18 enriched water has been recovered from IBA (Ion Beam Applications) recovery system followed by purification and then used in the production of 18 F-. The purification process has been carried out by irradiation with UV followed by a distillation under vacuum. After purification, 95% of water is recovered and organic compounds, radioisotopes, trace metals and gases are eliminated efficiently. Results show that there are no significant differences in (2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) production yield using purified water by the proposed method and new enriched water. Tritium was detected in the irradiated enriched water. Contamination precautions during purification should be considered. Tritium was not present in 18 FDG or Na- 18 F final products. (author)

Her-2 Positive Gastric Cancer Presented with Thrombocytopenia and Skin Involvement: A Case Report

Directory of Open Access Journals (Sweden)

Deniz Arslan

2014-01-01

Full Text Available Gastric cancer is the 5th most frequent cancer around the world and the 3rd most frequent reason of deaths due to cancer. Every year, about 1 million new cases are taking place, with varying geographical distribution. Gastric cancer is often metastatic to liver, lungs, and bones in hematogenous way, to peripheral lymph nodes in lymphogenous way, and to peripheral tissues in adjacency way, yet bone marrow (BM and cutaneous metastasis are quite seldom. Pancytopenia is a more frequent finding identified in BM metastasis of solid organ cancers, and isolated thrombocytopenia is less often. The human epidermal growth factor 2 (HER-2 is positive in gastric cancer at a rate of 7–34%. Here, we have presented our HER-2 positive gastric cancer incident which presented with BM and cutaneous metastasis, and has no 18F-fluoro-2-deoxi-D-glucose (FDG involvement except bone metastases.

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...

Advantages and pitfalls of 18F-fluoro-2-deoxy-D-glucose positron emission tomography in detecting locally residual or recurrent nasopharyngeal carcinoma: comparison with magnetic resonance imaging

International Nuclear Information System (INIS)

Chan, Sheng-Chieh; Chang, Yu-Chen; Yen, Tzu-Chen; Ng, Shu-Hang; Chang, Joseph Tung-Chieh; Lin, Chien-Yu; Chen, Yen-Chao; Hsu, Cheng-Lung; Wang, Hung-Ming; Liao, Chun-Ta

2006-01-01

This prospective study was designed to elucidate the advantages and pitfalls of 18 F-FDG PET in detecting locally residual/recurrent nasopharyngeal carcinoma (NPC) in comparison with MRI. We recruited NPC patients from two ongoing prospective trials. One is being performed to evaluate suspected local recurrence (group A) and the other to assess local treatment response 3 months after therapy (group B). Both groups received 18 F-FDG PET and head and neck MRI. The gold standard was histopathology or clinical/imaging follow-up. An optimal cut-off standardised uptake value (SUV) was retrospectively determined. From January 2002 to August 2004, 146 patients were eligible. Thirty-four were from group A and 112 from group B. In all, 26 had locally recurrent/residual tumours. Differences in detection rate between 18 F-FDG PET and MRI were not statistically significant in either group. However, 18 F-FDG PET showed significantly higher specificity than MRI in detecting residual tumours among patients with initial T4 disease (p=0.04). In contrast, the specificity of 18 F-FDG PET for patients with an initial T1-2 tumour treated with intracavitary brachytherapy (ICBT) was significantly lower than that for patients not treated by ICBT (72.2% vs 98.1%, p=0.003). At an SUV cut-off of 4.2, PET showed an equal and a higher accuracy compared with MRI in groups A and B, respectively. 18 F-FDG PET is superior to MRI in identifying locally residual NPC among patients with initial T4 disease but demonstrates limitations in assessing treatment response in patients with initial T1-2 disease after ICBT. A cut-off SUV is a useful index for aiding in the visual detection of locally residual/recurrent NPC. (orig.)

Separate and concurrent use of 2-deoxy-D-glucose and 3-bromopyruvate in pancreatic cancer cells.

Science.gov (United States)

Xiao, Huijie; Li, Shasha; Zhang, Dapeng; Liu, Tongjun; Yu, Ming; Wang, Feng

2013-01-01

Unrestrained glycolysis characterizes energy meta-bolism in cancer cells. Thus, antiglycolytic reagents such as 2-deoxy-D-glucose (2-DG) and 3-bromopyruvate (3-BrPA) may be used as anticancer drugs. In the present study, we examined the anticancer effects of 2-DG and 3-BrPA in pancreatic cancer cells and investigated whether these effects were regulated by hypoxia-inducible factor-1α (HIF-1α). To this end, 2-DG and 3-BrPA were administered to wild-type (wt) MiaPaCa2 and Panc-1 pancreatic cancer cells that were incubated under hypoxic (HIF-1α-positive) or normoxic (HIF-1α-negative) conditions. In addition, 2-DG and 3-BrPA were also administered to si-MiaPaCa2 and si-Panc-1 cells that lacked HIF-1α as a result of RNA interference. Following drug exposure, cell population was measured using a viability assay. Both HIF-1α-positive and HIF-1α-negative MiaPaCa2 cells were further studied for their expression of Cu/Zn-superoxide dismutase (SOD1) and poly(ADP-ribose) polymerase (PARP) and for their contents of ATP and fumarate. In the viability assay, either 2-DG or 3-BrPA decreased the tested cells. Concurrent use of 2-DG and 3-BrPA resulted in a greater decrease of cells and also facilitated ATP depletion. In addition, 3-BrPA was seen to both decrease SOD1 and increase fumarate, which suggests that the reagent impaired the mitochondria. 3-BrPA also decreased both full-length PARP and cleaved PARP, which suggests that 3-BrPA-induced decrease in cell population was a result of cell necrosis rather than apoptosis. When HIF-1α was induced in wt-MiaPaCa2 cells by hypoxia, some effects of 2-DG and 3-BrPA were attenuated. We conclude that: i) concurrent use of 2-DG and 3-BrPA has better anticancer effects in pancreatic cancer cells, ii) 3-BrPA impairs the mitochondria of pancreatic cancer cells and induces cell necrosis, and iii) HIF-1α regulates the anticancer effects of 2-DG and 3-BrPA in pancreatic cancer cells.

Cloning and characterization of a thermostable 2- deoxy-D-ribose-5 ...

African Journals Online (AJOL)

Analysis of the presumptive 2-deoxy-D-ribose 5-phosphate aldolase gene from Aciduliprofundum boonei revealed an open reading frame (ORF) encoding 222 amino acids, which was subcloned and then expressed in Escherichia coli. The recombinant DERA protein was purified to apparent homogeneity. The enzyme ...

Computer-assisted three-dimensional reconstructions of [14C]-2-deoxy-D-glucose metabolism in cat lumbosacral spinal cord following cutaneous stimulation of the hindfoot

International Nuclear Information System (INIS)

Crockett, D.P.; Smith, W.K.; Proshansky, E.; Kauer, J.S.; Stewart, W.B.; Woodward, D.J.; Schlusselberg, D.S.; Egger, M.D.

1989-01-01

We report on computer-assisted three-dimensional reconstruction of spinal cord activity associated with stimulation of the plantar cushion (PC) as revealed by [14C]-2-deoxy-D-glucose (2-DG) serial autoradiographs. Moderate PC stimulation in cats elicits a reflex phasic plantar flexion of the toes. Four cats were chronically spinalized at about T6 under barbiturate anesthesia. Four to 11 days later, the cats were injected (i.v.) with 2-DG (100 microCi/kg) and the PC was electrically stimulated with needle electrodes at 2-5 times threshold for eliciting a reflex. Following stimulation, the spinal cord was processed for autoradiography. Subsequently, autoradiographs, representing approximately 8-18 mm from spinal segments L6-S1, were digitized for computer analysis and 3-D reconstruction. Several strategies of analysis were employed: (1) Three-dimensional volume images were color-coded to represent different levels of functional activity. (2) On the reconstructed volumes, virtual sections were made in the horizontal, sagittal, and transverse planes to view regions of 2-DG activity. (3) In addition, we were able to sample different regions within the grey and white matter semi-quantitatively (i.e., pixel intensity) from section to section to reveal differences between ipsi- and contralateral activity, as well as possible variation between sections. These analyses revealed 2-DG activity associated with moderate PC stimulation, not only in the ipsilateral dorsal horn as we had previously demonstrated, but also in both the ipsilateral and contralateral ventral horns, as well as in the intermediate grey matter. The use of novel computer analysis techniques--combined with an unanesthetized preparation--enabled us to demonstrate that the increased metabolic activity in the lumbosacral spinal cord associated with PC stimulation was much more extensive than had heretofore been observed

Identification of rare 6-deoxy-D-altrose from an edible mushroom (Lactarius lividatus).

Science.gov (United States)

Tako, Masakuni; Dobashi, Yahiko; Tamaki, Yukihiro; Konishi, Teruko; Yamada, Masashi; Ishida, Hideharu; Kiso, Makoto

2012-03-01

6-Deoxy-L-altrose is well known as a constituent sugar moiety of lipopolysaccharides in Gram-negative bacteria. However, its isomer, 6-deoxy-D-altrose, is little known. Identification of 6-deoxy-D-altrose isolated from a polysaccharide extracted from an edible mushroom (Lactarius lividatus), its comparison with chemically synthesized 6-deoxy-D-altrose using (1)H and (13)C NMR including COSY, HMQC spectroscopy, and investigation of its specific optical rotation were all conducted in this study. The 6-deoxy-hexose isolated from acid hydrolysate of the polysaccharide extracted from L. lividatus was involved in four anomeric isomers (α-pyranose and β-pyranose, and α-furanose and β-furanose), as was chemically synthesized 6-deoxy-d-altrose in an aqueous solution because of mutarotation. Almost all signals of 1D ((1)H NMR and (13)C NMR) and 2D (COSY and HMQC)-NMR spectra agreed with those of the authentic 6-deoxy-D-altrose. The specific optical rotation [α](589) of 6-deoxy-sugar showed a value of +18.2°, which was in agreement with that of authentic 6-deoxy-D-altrose. Consequently, 6-deoxy-hexose was identified as the 6-deoxy-D-altrose. This work is the first complete identification of 6-deoxy-D-altrose in a natural environment. Copyright © 2012 Elsevier Ltd. All rights reserved.

Coupled Imaging with [18F]FBB and [18F]FDG in AD Subjects Show a Selective Association Between Amyloid Burden and Cortical Dysfunction in the Brain.

Science.gov (United States)

Chiaravalloti, Agostino; Castellano, Anna Elisa; Ricci, Maria; Barbagallo, Gaetano; Sannino, Pasqualina; Ursini, Francesco; Karalis, Georgios; Schillaci, Orazio

2018-02-05

The present study was aimed to investigate the relationships between dysfunction of cortical glucose metabolism as detectable by means of 2-deoxy-2-[ 18 F]fluoro -D-glucose ([ 18 F]FDG) positron emission tomography/x-ray computed tomography (PET/CT) and amyloid burden as detectable by means of 4-{(E)-2-[4-(2-{2-[2-[ 18 F]fluoroethoxy]ethoxy}ethoxy)phenyl]vinyl}-N-methylaniline (florbetaben; [ 18 F]FBB) in a group of patients affected by Alzheimer's disease (AD). We examined 38 patients newly diagnosed with AD according to the NINCDS-ADRDA criteria. All the subjects underwent a PET/CT scan using both [ 18 F]FDG and [ 18 F]FBB with an average interval of 1 month. We used statistical parametric mapping (SPM8) implemented in Matlab R2012b and WFU pickatlas for the definition of a region of interest (ROI) mask including the whole cortex. These data were then normalized on the counts of the cerebellum and then used for a regression analysis on [ 18 F]FDG scans in SPM. Furthermore, 58 control subjects were used as control group for [ 18 F]FDG PET/CT scans. SPM analysis in AD patients showed a significant negative correlation between [ 18 F] FBB and [ 18 F] FDG uptake in temporal and parietal lobes bilaterally. Of note, these areas in AD patients displayed a marked glucose hypometabolism compared to control group. Combined imaging with [ 18 F]FBB and [ 18 FFDG shows that amyloid burden in the brain is related to cortical dysfunction of temporal and parietal lobes in AD.

[18F]FDG and [18F]FLT positron emission tomography imaging following treatment with belinostat in human ovary cancer xenografts in mice

DEFF Research Database (Denmark)

Jensen, Mette Munk; Erichsen, Kamille Dumong; Johnbeck, Camilla Bardram

2013-01-01

Belinostat is a histone deacetylase inhibitor with anti-tumor effect in several pre-clinical tumor models and clinical trials. The aim of the study was to evaluate changes in cell proliferation and glucose uptake by use of 3'-deoxy-3'-[(18)F]fluorothymidine ([18F]FLT) and 2-deoxy-2-[(18)F]fluoro-......]fluoro-D-glucose ([18F]FDG) positron emission tomography (PET) following treatment with belinostat in ovarian cancer in vivo models....

Comparison of 18F-fluoromethylcholine and 2-deoxy-D-glucose in the distribution of tumor and inflammation

International Nuclear Information System (INIS)

Kubota, Kazuo; Furumoto, Shozo; Iwata, Ren; Fukuda, Hiroshi; Kawamura, Kazunori; Ishiwata, Kiichi

2006-01-01

The distribution characteristics of 18 F-fluoromethylcholine ( 18 F-choline) in tumor and inflammatory tissue were compared with those of 14 C or 3 H-2-deoxyglucose (2DG) as a substitute for fluorodeoxyglucose (FDG). A solid tumor model of AH109A in the back of Donryu rats and an aseptic inflammation model of turpentine oil injection subcutaneously in rats were used for experiments. Tissue distribution was examined at 5, 30 and 60 min after injection of a mixture of 18 F-choline and 3 H-2DG. Double-tracer high-resolution autoradiographs (ARGs) of tumor and inflammation were obtained using 18 F-choline and 14 C-2DG. Whole body (WB) ARG was performed with 18 F-choline. Tumor uptake of 18 F-choline reached a peak at 30 min, when the tumor to blood ratio was 5.1. Both tumor and inflammation uptake of 2DG were higher than those of 18 F-choline. 18 F-choline uptake by inflammation was lower than that by tumor. The tumor to brain uptake ratio was 5.7 with 18 F-choline and 1.2 with 2DG. In the ARG of inflammation, linear or ring-like structures of 2DG uptake were observed in the wall of the abscess, but were not identified with 18 F-choline. Photomicrography showed that the uptake was limited to granulocytes, macrophages and fibroblasts, consistent with sub-acute or chronic inflammation. 18 F-choline uptake by inflammation was lower than that of 2DG in the tissue distribution study, and 18 F-choline uptake by abscess wall was significantly lower than that of 2DG in the autoradiography study. Our results may suggest the feasibility of 18 F-choline-PET imaging for the differential diagnosis of cancer and chronic inflammation in lung and brain. (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)

[18F]CFA as a clinically translatable probe for PET imaging of deoxycytidine kinase activity.

Science.gov (United States)

Kim, Woosuk; Le, Thuc M; Wei, Liu; Poddar, Soumya; Bazzy, Jimmy; Wang, Xuemeng; Uong, Nhu T; Abt, Evan R; Capri, Joseph R; Austin, Wayne R; Van Valkenburgh, Juno S; Steele, Dalton; Gipson, Raymond M; Slavik, Roger; Cabebe, Anthony E; Taechariyakul, Thotsophon; Yaghoubi, Shahriar S; Lee, Jason T; Sadeghi, Saman; Lavie, Arnon; Faull, Kym F; Witte, Owen N; Donahue, Timothy R; Phelps, Michael E; Herschman, Harvey R; Herrmann, Ken; Czernin, Johannes; Radu, Caius G

2016-04-12

Deoxycytidine kinase (dCK), a rate-limiting enzyme in the cytosolic deoxyribonucleoside (dN) salvage pathway, is an important therapeutic and positron emission tomography (PET) imaging target in cancer. PET probes for dCK have been developed and are effective in mice but have suboptimal specificity and sensitivity in humans. To identify a more suitable probe for clinical dCK PET imaging, we compared the selectivity of two candidate compounds-[(18)F]Clofarabine; 2-chloro-2'-deoxy-2'-[(18)F]fluoro-9-β-d-arabinofuranosyl-adenine ([(18)F]CFA) and 2'-deoxy-2'-[(18)F]fluoro-9-β-d-arabinofuranosyl-guanine ([(18)F]F-AraG)-for dCK and deoxyguanosine kinase (dGK), a dCK-related mitochondrial enzyme. We demonstrate that, in the tracer concentration range used for PET imaging, [(18)F]CFA is primarily a substrate for dCK, with minimal cross-reactivity. In contrast, [(18)F]F-AraG is a better substrate for dGK than for dCK. [(18)F]CFA accumulation in leukemia cells correlated with dCK expression and was abrogated by treatment with a dCK inhibitor. Although [(18)F]CFA uptake was reduced by deoxycytidine (dC) competition, this inhibition required high dC concentrations present in murine, but not human, plasma. Expression of cytidine deaminase, a dC-catabolizing enzyme, in leukemia cells both in cell culture and in mice reduced the competition between dC and [(18)F]CFA, leading to increased dCK-dependent probe accumulation. First-in-human, to our knowledge, [(18)F]CFA PET/CT studies showed probe accumulation in tissues with high dCK expression: e.g., hematopoietic bone marrow and secondary lymphoid organs. The selectivity of [(18)F]CFA for dCK and its favorable biodistribution in humans justify further studies to validate [(18)F]CFA PET as a new cancer biomarker for treatment stratification and monitoring.

Simultaneous formation of 3-deoxy-d-threo-hexo-2-ulose and 3-deoxy-d-erythro-hexo-2-ulose during the degradation of d-glucose derived Amadori rearrangement products: Mechanistic considerations.

Science.gov (United States)

Kaufmann, Martin; Krüger, Sophie; Mügge, Clemens; Kroh, Lothar W

2018-03-22

Analyzing classical model reaction systems of Amadori rearrangement products (ARP) it became apparent that the formation of 3-deoxy-d-threo-hexo-2-ulose (3-deoxygalactosone, 3-DGal) during the degradation of ARPs is highly dependent on pH and the amino acid residue of the respective ARP. Based on a detailed analysis of the NMR chemical shifts of the sugar moieties of different ARPs, it could be derived that the formation of 3-DGal is sensitive to the stability of a co-operative hydrogen bond network which involves HO-C3, the deprotonated carboxyl functionality and the protonated amino nitrogen of the amino acid substituent. Participating in this bond network, HO-C3 is partially protonated which facilitates the elimination of water at C3. Based on that, a new mechanism of 3-deoxyglycosone formation is proposed. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effects of 2-deoxy-D-glucose, oligomycin and theophylline on in vitro glycerol metabolism in rat adipose tissue: response to insulin and epinephrine

Energy Technology Data Exchange (ETDEWEB)

Dominguez, M C; Herrera, E [Barcelona Univ. (Spain). Catedra de Fisiologia General

1976-01-01

The effects of 2-deoxy-D-glucose (2DG), oligomycin and theophylline on the in vitro production and metabolism of glycerol and its response to insulin and epinephrine were studied in epididymal fat pads from fed rats. 2-DG failed to affect basic or epinephrine-stimulated glycerol production but decreased the uptake of 1-/sup 14/C-glycerol by the tissue and its conversion to glyceride-glycerol. Oligomycin also failed to affect the basic production of glycerol, but it inhibited the affect of epinephrine on this parameter as well as the uptake and utilization of 1-/sup 14/C-glycerol. Theophylline enhanced the production of glycerol by the tissue, and this effect was not further augmented by epinephrine. Theophylline also inhibited the uptake and utilization of 1-/sup 14/C-glycerol; the most pronounced effect of theophylline was observed in the formation of /sup 14/C-fatty acids from 1-/sup 14/C-glycerol in the presence of glucose. Insulin, but not epinephrine, decreased the inhibitory effect of theophylline on glycerol utilization. It is concluded that these compounds affect the ability of adipose tissue to metabolize glycerol more intensely than the ability to release it through lipolysis. The pathway for glycerol utilization in adipose tissue appears to be more sensitive to changes in the availability of ATP than the mechanisms for the release of glycerol from the tissue.

Difference in prognostic significance of maximum standardized uptake value on [18F]-fluoro-2-deoxyglucose positron emission tomography between adenocarcinoma and squamous cell carcinoma of the lung

International Nuclear Information System (INIS)

Tsutani, Yasuhiro; Miyata, Yoshihiro; Misumi, Keizo; Ikeda, Takuhiro; Mimura, Takeshi; Hihara, Jun; Okada, Morihito

2011-01-01

This study evaluates the prognostic significance of [18F]-fluoro-2-deoxyglucose positron emission tomography/computed tomography findings according to histological subtypes in patients with completely resected non-small cell lung cancer. We examined 176 consecutive patients who had undergone preoperative [18F]-fluoro-2-deoxyglucose-positron emission tomography/computed tomography imaging and curative surgical resection for adenocarcinoma (n=132) or squamous cell carcinoma (n=44). Maximum standardized uptake values for the primary lesions in all patients were calculated as the [18F]-fluoro-2-deoxyglucose uptake and the surgical results were analyzed. The median values of maximum standardized uptake value for the primary tumors were 2.60 in patients with adenocarcinoma and 6.95 in patients with squamous cell carcinoma (P 6.95 (P=0.83) among patients with squamous cell carcinoma, 2-year disease-free survival rates were 93.9% for maximum standardized uptake value ≤3.7 and 52.4% for maximum standardized uptake value >3.7 (P<0.0001) among those with adenocarcinoma, and notably, 100 and 57.2%, respectively, in patients with Stage I adenocarcinoma (P<0.0001). On the basis of the multivariate Cox analyses of patients with adenocarcinoma, maximum standardized uptake value (P=0.008) was a significantly independent factor for disease-free survival as well as nodal metastasis (P=0.001). Maximum standardized uptake value of the primary tumor was a powerful prognostic determinant for patients with adenocarcinoma, but not with squamous cell carcinoma of the lung. (author)

Basal 18F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography as a prognostic biomarker in patients with locally advanced breast cancer

International Nuclear Information System (INIS)

Garcia Vicente, Ana Maria; Soriano Castrejon, Angel; Lopez-Fidalgo, Jesus Fernando; Amo-Salas, Mariano; Mar Munoz Sanchez, Maria del; Alvarez Cabellos, Ruth; Espinosa Aunion, Ruth

2015-01-01

To explore the relationship between basal 18 F-FDG PET/CT information in breast tumours and survival in locally advanced breast cancer (LABC). This prospective, multicentre study included 198 women diagnosed with LABC. All patients underwent 18 F-FDG PET/CT prior to treatment. The maximum standardized uptake value (SUVmax) in tumor (T), lymph nodes (N) and the N/T ratio was obtained in all cases. Stage according to PET/CT imaging (metabolic stage) and conventional imaging techniques (clinical stage) was established. During follow-up, patient status was established (disease free status or not). The relationship between all the variables and overall survival (OS) and disease-free survival (DFS) was analysed using the Kaplan-Meier and Cox regression methods. A ROC analysis was performed to obtain a cut-off value of SUVmax that was useful in the prediction of outcome. The mean SUVmax ± SD values in the primary tumour, lymph nodes and the SUVmax N/T index were 7.40 ± 5.57, 4.17 ± 4.74 and 0.73 ± 1.20, respectively. Higher semiquantitative metabolic values were found in more advanced metabolic and clinical stages. During follow-up, 78.4 % of patients were free of disease. Significant relationships were observed between SUVT and SUVN and patient status. With respect to OS and DFS, significant differences were detected for the metabolic stage. Kaplan-Meier analysis revealed that using the cut-off values, a primary-tumour SUVmax ≥ 6.05 or a nodal SUVmax ≥2.25 were significantly correlated with DFS and OS. PET imaging with 18 F-FDG offers prognostic information for LABC that can be obtained preoperatively and noninvasively. (orig.)

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

Ketosis proportionately spares glucose utilization in brain.

Science.gov (United States)

Zhang, Yifan; Kuang, Youzhi; Xu, Kui; Harris, Donald; Lee, Zhenghong; LaManna, Joseph; Puchowicz, Michelle A

2013-08-01

The brain is dependent on glucose as a primary energy substrate, but is capable of utilizing ketones such as β-hydroxybutyrate and acetoacetate, as occurs with fasting, starvation, or chronic feeding of a ketogenic diet. The relationship between changes in cerebral metabolic rates of glucose (CMRglc) and degree or duration of ketosis remains uncertain. To investigate if CMRglc decreases with chronic ketosis, 2-[(18)F]fluoro-2-deoxy-D-glucose in combination with positron emission tomography, was applied in anesthetized young adult rats fed 3 weeks of either standard or ketogenic diets. Cerebral metabolic rates of glucose (μmol/min per 100 g) was determined in the cerebral cortex and cerebellum using Gjedde-Patlak analysis. The average CMRglc significantly decreased in the cerebral cortex (23.0±4.9 versus 32.9±4.7) and cerebellum (29.3±8.6 versus 41.2±6.4) with increased plasma ketone bodies in the ketotic rats compared with standard diet group. The reduction of CMRglc in both brain regions correlates linearly by ∼9% for each 1 mmol/L increase of total plasma ketone bodies (0.3 to 6.3 mmol/L). Together with our meta-analysis, these data revealed that the degree and duration of ketosis has a major role in determining the corresponding change in CMRglc with ketosis.

Radiopharmacological evaluation of 6-deoxy-6-[{sup 18}F]fluoro-D-fructose as a radiotracer for PET imaging of GLUT5 in breast cancer

Energy Technology Data Exchange (ETDEWEB)

Wuest, Melinda, E-mail: mwuest@ualberta.c [Department of Oncology, University of Alberta - Cross Cancer Institute, Edmonton, AB-T6G 1Z2 (Canada); Trayner, Brendan J. [Department of Physiology, University of Alberta, Edmonton, AB-T6G 1Z2 (Canada); Grant, Tina N. [Department of Physiology, University of Alberta, Edmonton, AB-T6G 1Z2 (Canada); Department of Chemistry, University of Alberta, Edmonton, AB-T6G 1Z2 (Canada); Jans, Hans-Soenke; Mercer, John R.; Murray, David [Department of Oncology, University of Alberta - Cross Cancer Institute, Edmonton, AB-T6G 1Z2 (Canada); West, Frederick G. [Department of Chemistry, University of Alberta, Edmonton, AB-T6G 1Z2 (Canada); McEwan, Alexander J.B.; Wuest, Frank [Department of Oncology, University of Alberta - Cross Cancer Institute, Edmonton, AB-T6G 1Z2 (Canada); Cheeseman, Chris I. [Department of Physiology, University of Alberta, Edmonton, AB-T6G 1Z2 (Canada)

2011-05-15

Introduction: Several clinical studies have shown low or no expression of GLUT1 in breast cancer patients, which may account for the low clinical specificity and sensitivity of 2-deoxy-2-[{sup 18}F]fluoro-D-glucose ([{sup 18}F]FDG) used in positron emission tomography (PET). Therefore, it has been proposed that other tumor characteristics such as the high expression of GLUT2 and GLUT5 in many breast tumors could be used to develop alternative strategies to detect breast cancer. Here we have studied the in vitro and in vivo radiopharmacological profile of 6-deoxy-6-[{sup 18}F]fluoro-D-fructose (6-[{sup 18}F]FDF) as a potential PET radiotracer to image GLUT5 expression in breast cancers. Methods: Uptake of 6-[{sup 18}F]FDF was studied in murine EMT-6 and human MCF-7 breast cancer cells over 60 min and compared to [{sup 18}F]FDG. Biodistribution of 6-[{sup 18}F]FDF was determined in BALB/c mice. Tumor uptake was studied with dynamic small animal PET in EMT-6 tumor-bearing BALB/c mice and human xenograft MCF-7 tumor-bearing NIH-III mice in comparison to [{sup 18}F]FDG. 6-[{sup 18}F]FDF metabolism was investigated in mouse blood and urine. Results: 6-[{sup 18}F]FDF is taken up by EMT-6 and MCF-7 breast tumor cells independent of extracellular glucose levels but dependent on the extracellular concentration of fructose. After 60 min, 30{+-}4% (n=9) and 12{+-}1% (n=7) ID/mg protein 6-[{sup 18}F]FDF was found in EMT-6 and MCF-7 cells, respectively. 6-deoxy-6-fluoro-D-fructose had a 10-fold higher potency than fructose to inhibit 6-[{sup 18}F]FDF uptake into EMT-6 cells. Biodistribution in normal mice revealed radioactivity uptake in bone and brain. Radioactivity was accumulated in EMT-6 tumors reaching 3.65{+-}0.30% ID/g (n=3) at 5 min post injection and decreasing to 1.75{+-}0.03% ID/g (n=3) at 120 min post injection. Dynamic small animal PET showed significantly lower radioactivity uptake after 15 min post injection in MCF-7 tumors [standard uptake value (SUV)=0

¹⁸F-FDG PET/CT-based early treatment response evaluation of nanoparticle-assisted photothermal cancer therapy

DEFF Research Database (Denmark)

Norregaard, Kamilla; Jørgensen, Jesper T.; Simón, Marina

2017-01-01

Within the field of nanoparticle-assisted photothermal cancer therapy, focus has mostly been on developing novel heat-generating nanoparticles with the right optical and dimensional properties. Comparison and evaluation of their performance in tumor-bearing animals are commonly assessed by changes...... in tumor volume; however, this is usually a late-occurring event. This study implements 2-deoxy-2-[F-18]fluoro-D-glucose positron emission tomography imaging to perform early evaluation of the treatment outcome of photothermal therapy. Silica-gold nanoshells (NS) are administered intravenously to nude mice...

2'-deoxy-5,6-dihydro-5-azacytidine-a less toxic alternative of 2'-deoxy-5-azacytidine. A comparative study of hypomethylating potential

Czech Academy of Sciences Publication Activity Database

Matoušová, Marika; Votruba, Ivan; Otmar, Miroslav; Tloušťová, Eva; Günterová, Jana; Mertlíková-Kaiserová, Helena

2011-01-01

Roč. 6, č. 6 (2011), s. 769-776 ISSN 1559-2294 R&D Projects: GA MŠk 1M0508 Institutional research plan: CEZ:AV0Z40550506 Keywords : epigenetic therapy * nucleoside analogs * DNA methylation * 2'-deoxy-5-azacytidine * 2'-deoxy-5,6-dihydro-5-azacytidine Subject RIV: CE - Biochemistry Impact factor: 4.318, year: 2011

Breast hemangioma mimicking metastasis at PET-CT

Energy Technology Data Exchange (ETDEWEB)

Vieira, Sabas Carlos [Universidade Federal do Piaui (UFPI), Teresina, PI (Brazil). Fac. de Medicina; Silva, Jucelia Saraiva e [MedImagem, Teresina, PI (Brazil). Clinica Medica; Madeira, Eveline Brandao; Franca, Julio Cesar Queiroz de; Martins Filho, Sebastiao Nunes [Universidade Federal do Piaui (UFPI), Teresina, PI (Brazil)

2011-11-15

Breast hemangioma is a rare benign tumor that presents either absent or low {sup 18}F-fluoro-2-deoxy-D-glucose (FDG) uptake at positron emission tomography (PET). The authors report the case of a breast nodule pathologically compatible with hemangioma in a woman whose PET-scan has demonstrated increased FDG uptake (simulating a malignant tumor). A brief review of factors leading to false positive and false negative PET results is also undertaken. (author)

Protecting-Group-Free Synthesis of 2-Deoxy-Aza-Sugars

Directory of Open Access Journals (Sweden)

Mattie Simon Maria Timmer

2009-12-01

Full Text Available The protecting-group-free asymmetric synthesis of 1,2,4-trideoxy-1,4-imino-L-xylitol is readily achieved in five steps from 2-deoxy-D-ribose and with an overall yield of 48%. Key in this synthesis is the application of our recently developed Vasella-reductive amination and carbamate annulation methodologies to the synthesis of 2-deoxy-aza-sugars. The carbamate annulation occurred with excellent yield and diastereoselectively (>20:1 d.r., in favour of the 3,4-cis isomer.

A PET study of 18FDG uptake in soft tissue masses

International Nuclear Information System (INIS)

Lodge, M.A.; Marsden, P.K.; Cronin, B.F.; O'Doherty, M.J.; Lucas, J.D.; Smith, M.A.

1999-01-01

A study was performed with the aim of investigating some of the methodological factors affecting the ability of quantitative 2-[ 18 F]-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography to assess tumour malignancy. Twenty-nine patients with soft tissue masses were studied using a 6-hour scanning protocol and various indices of glucose metabolism were compared with histological grade. Significant differences were observed in the time-activity response of benign and high-grade tumours. High-grade sarcomas were found to reach a peak activity concentration approximately 4 h after injection whereas benign lesions reached a maximum within 30 min. This translated to improved differentiation between these two tumour types using a standard uptake value (SUV) derived from images acquired at later times. An SUV measured 4 h post-injection was found to be as useful an index of tumour malignancy as the metabolic rate of FDG determined using either Patlak or non-linear regression techniques. Each of these indices had a sensitivity and specificity of 100% and 76% respectively for the discrimination of high-grade sarcomas from benign tumours. (orig.)

Comparison of five segmentation tools for 18F-fluoro-deoxy-glucose-positron emission tomography-based target volume definition in head and neck cancer.

NARCIS (Netherlands)

Schinagl, D.A.X.; Vogel, W.V.; Hoffmann, A.L.; Dalen, J.A. van; Oyen, W.J.G.; Kaanders, J.H.A.M.

2007-01-01

PURPOSE: Target-volume delineation for radiation treatment to the head and neck area traditionally is based on physical examination, computed tomography (CT), and magnetic resonance imaging. Additional molecular imaging with (18)F-fluoro-deoxy-glucose (FDG)-positron emission tomography (PET) may

Basal {sup 18}F-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography as a prognostic biomarker in patients with locally advanced breast cancer

Energy Technology Data Exchange (ETDEWEB)

Garcia Vicente, Ana Maria; Soriano Castrejon, Angel [University General Hospital, Nuclear Medicine Department, Ciudad Real (Spain); Lopez-Fidalgo, Jesus Fernando; Amo-Salas, Mariano [University of Castilla-La Mancha, Department of Mathematics, Ciudad Real (Spain); Mar Munoz Sanchez, Maria del [Virgen de la Luz Hospital, Oncology Department, Cuenca (Spain); Alvarez Cabellos, Ruth [Virgen de la Salud Hospital, Oncology Department, Toledo (Spain); Espinosa Aunion, Ruth [La Mancha Centro Hospital, Oncology Department, Ciudad Real (Spain)

2015-11-15

To explore the relationship between basal {sup 18}F-FDG PET/CT information in breast tumours and survival in locally advanced breast cancer (LABC). This prospective, multicentre study included 198 women diagnosed with LABC. All patients underwent {sup 18}F-FDG PET/CT prior to treatment. The maximum standardized uptake value (SUVmax) in tumor (T), lymph nodes (N) and the N/T ratio was obtained in all cases. Stage according to PET/CT imaging (metabolic stage) and conventional imaging techniques (clinical stage) was established. During follow-up, patient status was established (disease free status or not). The relationship between all the variables and overall survival (OS) and disease-free survival (DFS) was analysed using the Kaplan-Meier and Cox regression methods. A ROC analysis was performed to obtain a cut-off value of SUVmax that was useful in the prediction of outcome. The mean SUVmax ± SD values in the primary tumour, lymph nodes and the SUVmax N/T index were 7.40 ± 5.57, 4.17 ± 4.74 and 0.73 ± 1.20, respectively. Higher semiquantitative metabolic values were found in more advanced metabolic and clinical stages. During follow-up, 78.4 % of patients were free of disease. Significant relationships were observed between SUVT and SUVN and patient status. With respect to OS and DFS, significant differences were detected for the metabolic stage. Kaplan-Meier analysis revealed that using the cut-off values, a primary-tumour SUVmax ≥ 6.05 or a nodal SUVmax ≥2.25 were significantly correlated with DFS and OS. PET imaging with {sup 18}F-FDG offers prognostic information for LABC that can be obtained preoperatively and noninvasively. (orig.)

2-Deoxy-D-glucose treatment of endothelial cells induces autophagy by reactive oxygen species-mediated activation of the AMP-activated protein kinase.

Directory of Open Access Journals (Sweden)

Qilong Wang

2011-02-01

Full Text Available Autophagy is a cellular self-digestion process activated in response to stresses such as energy deprivation and oxidative stress. However, the mechanisms by which energy deprivation and oxidative stress trigger autophagy remain undefined. Here, we report that activation of AMP-activated protein kinase (AMPK by mitochondria-derived reactive oxygen species (ROS is required for autophagy in cultured endothelial cells. AMPK activity, ROS levels, and the markers of autophagy were monitored in confluent bovine aortic endothelial cells (BAEC treated with the glycolysis blocker 2-deoxy-D-glucose (2-DG. Treatment of BAEC with 2-DG (5 mM for 24 hours or with low concentrations of H(2O(2 (100 µM induced autophagy, including increased conversion of microtubule-associated protein light chain 3 (LC3-I to LC3-II, accumulation of GFP-tagged LC3 positive intracellular vacuoles, and increased fusion of autophagosomes with lysosomes. 2-DG-treatment also induced AMPK phosphorylation, which was blocked by either co-administration of two potent anti-oxidants (Tempol and N-Acetyl-L-cysteine or overexpression of superoxide dismutase 1 or catalase in BAEC. Further, 2-DG-induced autophagy in BAEC was blocked by overexpressing catalase or siRNA-mediated knockdown of AMPK. Finally, pretreatment of BAEC with 2-DG increased endothelial cell viability after exposure to hypoxic stress. Thus, AMPK is required for ROS-triggered autophagy in endothelial cells, which increases endothelial cell survival in response to cell stress.

Enriched Water-H{sub 2} {sup 18}O Purification to be Used in Routine {sup 18}FDG Production

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Al Rayyes, A. H. [Atomic Energy Commission of Syria, Chemistry Department, Cyclotron Division, Damascus (Syrian Arab Republic)

2009-07-01

Oxygen-18 enriched water has been recovered from IBA (Ion Beam Applications) recovery system followed by purification and then used in the production of {sup 18}F-. The purification process has been carried out by irradiation with UV followed by a distillation under vacuum. After purification, 95% of water is recovered and organic compounds, radioisotopes, trace metals and gases are eliminated efficiently. Results show that there are no significant differences in (2-deoxy-2-[{sup 18}F]fluoro-D-glucose ([{sup 18}F]FDG) production yield using purified water by the proposed method and new enriched water. Tritium was detected in the irradiated enriched water. Contamination precautions during purification should be considered. Tritium was not present in {sup 18}FDG or Na-{sup 18}F final products. (author)

Unilateral Muscle Artifacts due to Non-compliance During Uptake Phase of 18F-FDG PET/CT in an Oncologic Patient

Directory of Open Access Journals (Sweden)

William Makis

2018-02-01

Full Text Available A 49-year-old male patient with a prior history of poor compliance with medical appointments was referred for an 18F-fluoro-2-deoxy-D-glucose (18F-FDG positron emission tomography/computed tomography (PET/CT for the staging of a rectal squamous cell carcinoma. The PET/CT showed unilateral diffuse skeletal muscle 18F-FDG uptake as well as bilateral salivary gland uptake artifacts, suggestive of non-compliance with patient preparation instructions. The PET/CT nurse noted that during the 18F-FDG uptake phase, the patient appeared intoxicated, and she found two beer cans hidden in the waste disposal beside his chair just prior to imaging. The patient only admitted to eating a cookie approximately 30 minutes after the injection of 18F-FDG PET/CT and denied consuming alcohol during the uptake phase. We present the imaging findings of non-compliance with patient instructions during the uptake phase of 18F-FDG.

Ionizing radiation: down regulation of 'atm' by 2 Deoxy-D-Glucose: a dose and time dependent study

International Nuclear Information System (INIS)

Lahiri, S.S.; Saxena, N.; Hambarde, S.

2014-01-01

Exposure to Ionizing Radiation (IR) cause cell death, but it also help in radio-sensitization of cancer cells, by causing oxidative stress and DNA damage, primarily by double strand breaks. Ataxia telangiectasia mutated (atm) gene is involved in DNA double strand breaks, sensory and repair pathways. Therefore, inhibition of its expression, can lead to useful radio-sensitization of cancerous cells. Metabolic inhibitor 2-Deoxy-D-Glucose (2-DG) block glycolysis and modulates protein glycosylation (2-DG). This cause sensitization of cancer cells to radiation, which help in effective reduction in the essential dose of therapeutic ionizing radiation required for the treatment of cancer. The transcription factor Sp-1 involved, is also down-regulated by 2-DG. We have studied the effect of 2-DG at varied concentrations, applied at different pre, simultaneous as well as post irradiation time intervals with 2 Gy, 5 Gy or 10 Gy (lethal dose) of ionizing radiations. Expressions of 'atm' gene in response to the drug and/or IR of different doses were studied. Response was studied at different post irradiation time intervals, in the levels of mRNA, protein and cell survival. It was observed that exposure of human glioma cells (BMG1) to 2 Gy, 5 Gy or 10 Gy of IR alone, had differential and dose dependent effect on 'atm' expression. The 'atm' level was significantly down regulated by 2-DG, in non-irradiated as well as gamma ray irradiated cells. It was observed that BMG1 cells when treated with 2-DG and exposed to irradiation, there was no net significant alteration (normalcy was restored) in the expression level of 'atm'. It was also observed that the extent of down-regulation by pre-treatment with 2-DG, was greater than post-treatment. This work has great significance in the application of clinically relevant low dose radiotherapy for the treatment of cancer. (author)

{sup 18}F-FDG metabolism in a rat model of chronic infarction. A 17-sector semiquantitative analysis

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Penuelas, I. [Clinica Universitaria de Navarra, Pamplona (Spain). Dept. of Nuclear Medicine; MicroPET Research Unit CIMA-CUN, Pamplona (Spain); Abizanda, G.; Mazo, M.; Prosper, F. [Clinica Universitaria de Navarra, Pamplona (Spain). Hematology and Cell Therapy Service; Navarra Univ., Pamplona (Spain). Foundation for Applied Medical Research; Garcia-Velloso, M.J.; Marti-Climent, J.M.; Richter, J.A. [Clinica Universitaria de Navarra, Pamplona (Spain). Dept. of Nuclear Medicine; Gavira, J.J.; Barba, J. [Clinica Universitaria de Navarra, Pamplona (Spain). Cardiology and Cardiovascular Surgery; Ecay, M.; Collantes, M. [MicroPET Research Unit CIMA-CUN, Pamplona (Spain); Garcia de Jalon, J.A.; Garcia-Rodriguez, A. [Zaragoza Univ. (Spain). Dept. of Animal Pathology

2007-07-01

Strategies to establish the functional benefit of cell therapy in cardiac regeneration and the potential mechanism are needed. Aims: Development of a semi-quantitative method for non invasive assessment of cardiac viability and function in a rat model of myocardial infarction (MI) based on the use of microPET. Animals, methods: Ten rats were subjected to myocardial imaging 2, 7, 14, 30, 60 and 90 days after left coronary artery ligation. Intravenous {sup 18}F-fluoro-2-deoxy-2-D-glucose ({sup 18}F-FDG) was administered and regional {sup 18}F activity concentrations per unit area were measured in 17 regions of interest (ROIs) drawn on cardiac polar maps. By comparing the differences in {sup 18}F uptake between baseline and each of the follow up time points, parametric polar maps of statistical significance (PPMSS) were calculated. Left ventricular ejection fraction (LVEF) was blindly assessed echocardiographically. All animals were sacrificed for histopathological analysis after 90 days. Results: The diagnostic quality of {sup 18}F-FDG microPET images was excellent. PPMSS demonstrated a statistically significant decrease in {sup 18}F concentrations as early as 48 hours after MI in 4 of the 17 ROIs (segments 7, 13, 16 and 17; p <0.05) that persisted throughout the study. Semi-quantitative analysis of {sup 18}F-FDG uptake correlated with echocardiographic decrease in LVEF (p <0.001). Conclusion: The use of PPMSS based on 18F-FDG-microPET provides valuable semi-quantitative information of heart glucose metabolism allowing for non-invasive follow up thus representing a useful strategy for assessment of novel therapies in cardiac regeneration. (orig.)

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

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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

Regional glucose metabolism using PETT in normal and psychiatric populations

International Nuclear Information System (INIS)

Brodie, J.D.; Wolf, A.P.; Volkow, N.

1982-01-01

The metabolism of 18 F-2-deoxy-2-fluoro-D-glucose ( 18 FDG) in 150 subjects including normals, schizophrenics, senile dementias, and primary affective disorders was studied. Some of the data analyzed to date are discussed

Deoxyfluoroketohexoses: 4-deoxy-4-fluoro-D-sorbose and -tagatose and 5-deoxy-5-fluoro-L-sorbose.

Science.gov (United States)

Rao, G V; Que, L; Hall, L D; Fondy, T P

1975-04-01

4-Deoxy-4-fluoro-alpha-D-sorbose (6) was prepared in crystalline form by the action of potassium hydrogen fluoride on 3,4-anhydro-1,2-O-isopropylidene-beta-D-psicopyranose (3) followed by deacetonation. Under identical conditions, 3,4-anhydro-1,2-O-isopropylidene-beta-D-tagatopyranose (7) underwent epoxide migration to give 4,5-anhydro-1,2-O-isopropylidene-beta-D-fructopyranose (12), which after deacetonation yielded 4-deoxy-4-fluoro-D-tagatose (15) and 5-deoxy-5-fluoro-alpha-L-sorbopyranose (16), the latter as the crystalline, free sugar. The action of glycol-cleavage reagents on the isopropylidene acetals of the deoxyfluoro sugars was consistent with the assigned structures. The structures were established by 13-C n.m.r. studies of the free deoxyfluoro sugars 6 and 16 and of the isopropylidene acetal 13, and by 1-H n.m.r. studies on the acetylated isopropylidene acetals 5 diacetate, 13 diacetate, and 14 diacetate. 5-Deoxy-5-fluoro-L-sorbose (16) was biologically active, producing in mice effects characteristic of deoxyfluorotrioses and of fluoroacetate. 4-Deoxy-4-fluoro-D-tagatose (15) and 4-deoxy-4-fluoro-D-sorbose (6) produced no apparent effects in mice up to a dose of 500mg/kg. The implications of these findings with respect to transport, phosphorylation, and the action of aldolase on ketohexoses are discussed.

A facile and rapid automated synthesis of 3'-deoxy-3'-[18F]fluorothymidine

International Nuclear Information System (INIS)

Tang Ganghua; Tang Xiaolan; Wen Fuhua; Wang Mingfang; Li Baoyuan

2010-01-01

Aim: To develop a simplified and fully automated synthesis procedure of 3'-deoxy-3'-[ 18 F]fluorothymidine ([ 18 F]FLT) using PET-MF-2V-IT-I synthesis module. Methods: Synthesis of [ 18 F]FLT was performed using PET-MF-2V-IT-I synthesis module by one-pot two-step reaction procedure, including nucleophilic fluorination of 3-N-t-butoxycarbonyl-1-[5'-O-(4,4'-dimethoxy triphenylmethyl)-2'-deoxy-3'-O-(4-nitrobenzenesulfonyl) -β-D-threopentofuranosyl]thymine (15 mg) as the precursor molecule with [ 18 F]fluoride, and subsequent hydrolysis of the protecting group with 1.0 M HCl at the same reaction vessel and purification with SEP PAK cartridges instead of the HPLC system. Results: The automated synthesis of [ 18 F]FLT with SEP PAK purification gave corrected radiochemical yield of 23.2±2.6% (n=6, uncorrected yield: 16-22%) and radiochemical purity of >97% within the total synthesis time of 35 min. Conclusion: The fully one-pot automated synthesis procedure with SEP PAK purification can be applied to the fully automated synthesis of [ 18 F]FLT using commercial [ 18 F]FDG synthesis module.

A prospective evaluation of the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography staging on survival for patients with locally advanced esophageal cancer

International Nuclear Information System (INIS)

Blackstock, A. William; Farmer, Michael R.; Lovato, James; Mishra, Girish; Melin, Susan A.; Oaks, Timothy; Aklilu, Mabea; Clark, Paige B.; Levine, Edward A.

2006-01-01

Purpose: To determine the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) in the staging and prognosis of patients with locally advanced esophageal cancer (LAEC). Methods and Materials: Between January 2000 and October 2004, all patients with LAEC evaluated in the Department of Radiation Oncology were considered for enrollment into a Phase II trial of preoperative chemoradiation. Entry required a staging whole-body FDG-PET scan. Results: One hundred ten consecutive patients were evaluated; 38 were ineligible for reasons including treatment elsewhere, prior malignancy, or refusal of treatment. After conventional staging (clinical examination, endoscopic ultrasound, and chest/abdominal computerized tomography), 33 patients were ineligible because of metastatic disease or poor performance status. Of the remaining 39 patients, 23 were confirmed to have LAEC after FDG-PET staging and were treated in the Phase II trial (Cohort I). Sixteen patients, however, had FDG-PET findings consistent with occult metastatic disease and were deemed ineligible for the trial but were treated with curative intent (Cohort II). The 2-year survival rate for the 23 patients in Cohort I was 64%, compared with 17% (p = 0.003) for patients in Cohort II (FDG-PET positive). Conclusions: More than one-third of patients determined to have LAEC with conventional staging were upstaged with the use of FDG-PET. Despite comparable therapy, upstaging with FDG-PET predicts poor 2-year survival

Analysis of metabolism of 6FDG: a PET glucose transport tracer

Energy Technology Data Exchange (ETDEWEB)

Muzic, Raymond F., E-mail: raymond.muzic@case.edu [Department of Radiology, Case Western Reserve University, Cleveland, OH 44106 (United States); Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106 (United States); Chandramouli, Visvanathan [Department of Radiology, Case Western Reserve University, Cleveland, OH 44106 (United States); Huang, Hsuan-Ming [Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106 (United States); Wu Chunying; Wang Yanming [Department of Radiology, Case Western Reserve University, Cleveland, OH 44106 (United States); Ismail-Beigi, Faramarz [Department of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States)

2011-07-15

Introduction: We are developing {sup 18}F-labeled 6-fluoro-6-deoxy-D-glucose ([{sup 18}F]6FDG) as a tracer of glucose transport. As part of this process it is important to characterize and quantify putative metabolites. In contrast to the ubiquitous positron emission tomography (PET) tracer {sup 18}F-labeled 2-fluoro-2-deoxy-D-glucose ([{sup 18}F]2FDG) which is phosphorylated and trapped intracellularly, the substitution of fluorine for a hydroxyl group at carbon-6 in [{sup 18}F]6FDG should prevent its phosphorylation. Consequently, [{sup 18}F]6FDG has the potential to trace the transport step of glucose metabolism without the confounding effects of phosphorylation and subsequent steps of metabolism. Herein the focus is to determine whether, and the degree to which, [{sup 18}F]6FDG remains unchanged following intravenous injection. Methods: Biodistribution studies were performed using 6FDG labeled with {sup 18}F or with the longer-lived radionuclides {sup 3}H and {sup 14}C. Tissues were harvested at 1, 6, and 24 h following intravenous administration and radioactivity was extracted from the tissues and analyzed using a combination of ion exchange columns, high-performance liquid chromatography, and chemical reactivity. Results: At the 1 h time-point, the vast majority of radioactivity in the liver, brain, heart, skeletal muscle, and blood was identified as 6FDG. At the 6-h and 24-h time points, there was evidence of a minor amount of radioactive material that appeared to be 6-fluoro-6-deoxy-D-sorbitol and possibly 6-fluoro-6-deoxy-D-gluconic acid. Conclusion: On the time scale typical of PET imaging studies radioactive metabolites of [{sup 18}F]6FDG are negligible.

Regional glucose metabolism using PETT in normal and psychiatric populations

Energy Technology Data Exchange (ETDEWEB)

Brodie, J.D.; Wolf, A.P.; Volkow, N.

1982-01-01

The metabolism of /sup 18/F-2-deoxy-2-fluoro-D-glucose (/sup 18/FDG) in 150 subjects including normals, schizophrenics, senile dementias, and primary affective disorders was studied. Some of the data analyzed to date are discussed.

Position emission tomography with or without computed tomography in the primary staging of Hodgkin's lymphoma

DEFF Research Database (Denmark)

Hutchings, Martin; Loft, Annika; Hansen, Mads

2006-01-01

BACKGROUND AND OBJECTIVES: In order to receive the most appropriate therapy, patients with Hodgkin's lymphoma (HL) must be accurately stratified into different prognostic staging groups. Computed tomography (CT) plays a pivotal role in the conventional staging. The aim of the present study...... was to investigate the value of positron emission tomography using 2-[18F]fluoro-2-deoxy-D-glucose (FDG-PET) and combined FDG-PET/CT for the staging of HL patients, and the impact on the choice of treatment. DESIGN AND METHODS: Ninety-nine consecutive, prospectively included patients had FDG-PET and CT...

FDG-PET in the clinical management of Hodgkin lymphoma

DEFF Research Database (Denmark)

Hutchings, Martin; Eigtved, Annika I; Specht, Lena

2004-01-01

Positron emission tomography (PET) is a molecular functional imaging technique that provides qualitative and quantitative information about the localization and activity of pathophysiological processes. The most commonly used tracer for oncological purposes is 2-[18F]fluoro-2-deoxy-d-glucose (FDG......). FDG-PET has within recent years become the most important nuclear medicine imaging modality in the management of lymphoma. This review summarizes the data published so far concerning the value of FDG-PET in staging, treatment monitoring, therapy planning, and follow-up of Hodgkin lymphoma (HL). FDG...

Reassessment of FDG uptake in tumor cells: High FDG uptake as a reflection of oxygen-independent glycolysis dominant energy production

Energy Technology Data Exchange (ETDEWEB)

Waki, A.; Fujibayashi, Y.; Yonekura, Y.; Sadato, N.; Ishii, Y.; Yokoyama, A

1997-10-01

To determine appropriate use of 2-[{sup 18}F]-fluoro-2-deoxy-D-glucose (FDG) in the diagnosis of malignant tumors, the mechanism of enhanced FDG uptake in tumor cells was reassessed using in vitro cultured cell lines and {sup 3}H-deoxyglucose (DG), in combination with possible parameters of aerobic and anaerobic energy production. The high DG uptake in the tumor cells reflected the dependency of energy production on anaerobic glycolysis, and paradoxically on low levels of aerobic oxidative phosphorylation in mitochondria. We discuss here factors underlying anaerobic glycolysis in tumor cells.

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.

Revisiting the prognostic value of preoperative 18F-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET) in early-stage (I and II) non-small cell lung cancers (NSCLC)

International Nuclear Information System (INIS)

Agarwal, Mohit; Brahmanday, Govinda; Bajaj, Sunil K.; Wong, Ching-Yee Oliver; Ravikrishnan, K.P.

2010-01-01

The aims were to determine if the maximum standardized uptake value (SUV max ) of the primary tumor as determined by preoperative 18 F-fluoro-2-deoxyglucose ( 18 F-FDG) positron emission tomography (PET) is an independent predictor of overall survival and to assess its prognostic value after stratification according to pathological staging. A retrospective clinicopathologic review of 363 patients who had a preoperative 18 F-FDG PET done before undergoing attempted curative resection for early-stage (I and II) non-small cell lung cancer (NSCLC) was performed. Patients who had received any adjuvant or neoadjuvant chemotherapy or radiation therapy were excluded. The primary outcome measure was duration of overall survival. Receiver-operating characteristic (ROC) curves were plotted to find out the optimal cutoff values of SUV max yielding the maximal sensitivity plus specificity for predicting the overall survival. Survival curves stratified by median SUV max and optimal cutoff SUV max were estimated by the Kaplan-Meier method and statistical differences were assessed using the log-rank test. Multivariate proportional hazards (Cox) regression analyses were applied to test the SUV max 's independency of other prognostic factors for the prediction of overall survival. The median duration of follow-up was 981 days (2.7 years). The median SUV max was 5.9 for all subjects, 4.5 for stage IA, 8.4 for stage IB, and 10.9 for stage IIB. The optimal cutoff SUV max was 8.2 for all subjects. No optimal cutoff could be established for specific stages. In univariate analyses, each doubling of SUV max [i.e., each log (base 2) unit increase in SUV max ] was associated with a 1.28-fold [95% confidence interval (CI): 1.03-1.59, p = 0.029] increase in hazard of death. Univariate analyses did not show any significant difference in survival by SUV max when data were stratified according to pathological stage (p = 0.119, p = 0.818, and p = 0.882 for stages IA, IB, and IIB, respectively

Retinoblastoma treatment: impact of the glycolytic inhibitor 2-deoxy-d-glucose on molecular genomics expression in LHBETATAG retinal tumors

Directory of Open Access Journals (Sweden)

Piña Y

2012-05-01

Full Text Available Yolanda Piña,1 Samuel K Houston,1 Timothy G Murray,1 Tulay Koru-Sengul,2,3 Christina Decatur,1 William K Scott,4 Lubov Nathanson,4 Jennifer Clarke,2 Theodore J Lampidis,51Bascom Palmer Eye Institute, 2Department of Epidemiology and Public Health, 3Sylvester Comprehensive Cancer Center, 4Department of Molecular Genomics, 5Department of Cell Biology and Anatomy, University of Miami Miller School of Medicine, Miami, FL, USAPurpose: The purpose of this study was to evaluate the effect of 2-deoxy-D-glucose (2-DG on the spatial distribution of the genetic expression of key elements involved in angiogenesis, hypoxia, cellular metabolism, and apoptosis in LHBETATAG retinal tumors.Methods: The right eye of each LHBETATAG transgenic mouse (n = 24 was treated with either two or six subconjunctival injections of 2-DG (500 mg/kg or saline control at 16 weeks of age. A gene expression array analysis was performed on five different intratumoral regions (apex, center, base, anterior-lateral, and posterior-lateral using Affymetrix GeneChip Mouse Gene 1.0 ST arrays. To test for treatment effects of each probe within each region, a two-way analysis of variance was used.Results: Significant differences between treatment groups (ie, 0, 2, and 6 injections were found as well as differences among the five retinal tumor regions evaluated (P < 0.01. More than 100 genes were observed to be dysregulated by ≥2-fold difference in expression between the three treatment groups, and their dysregulation varied across the five regions assayed. Several genes involved in pathways important for tumor cell growth (ie, angiogenesis, hypoxia, cellular metabolism, and apoptosis were identified.Conclusions: 2-DG was found to significantly alter the gene expression in LHBETATAG retinal tumor cells according to their location within the tumor as well as the treatment schedule. 2-DG's effects on genetic expression found here correlate with previous reported results on varied processes

Tumor response to ionizing radiation and combined 2-deoxy-D-glucose application in EATC tumor bearing mice: monitoring of tumor size and microscopic observations

International Nuclear Information System (INIS)

Latz, D.; Thonke, A.; Jueling-Pohlit, L.; Pohlit, W.

1993-01-01

The present study deals with the changes induced by two fractionation schedules (5x9 Gy and 10x4.5 Gy; 30 MeV-electrons) of ionizing radiations and 2-Deoxy-D-Glucose (2-DG) application on EATC tumor bearing swiss albino mice. The monitoring of tumor response was carried out by means of calliper measurement on the macroscopic level and by histopathological examination of tumor preparations stained with hematoxiline and eosine on the microscopic level. The tumor material was assessed at suitable intervals after treatment by killing the animals. The tumor response was analysed in the histological preparations and the thickness of the tumor band was determined quantitatively by an ocularmicrometric technique. Tumor damage was most extensive in the combined treated animals (5x9 Gy + 2-DG). Only in this group local tumor control was achievable. The histological analysis of tumor preparations revealed additional data about treatment-induced changes in the tumor compared to the measurement of the tumor volume with mechanical callipers. We also found that the treatment outcome could be predicted from the histopathological analysis. It is concluded that studies involving histopathological examinations may give some insight into the way cancer is controlled by radiotherapy and may be of value in prognosis and selection of treatment in patients. (orig.) [de

Synthesis and preclinical characterization of 1-(6'-deoxy-6'-[18F]fluoro-β-d-allofuranosyl)-2-nitroimidazole (β-6'-[18F]FAZAL) as a positron emission tomography radiotracer to assess tumor hypoxia.

Science.gov (United States)

Wanek, Thomas; Kreis, Katharina; Križková, Petra; Schweifer, Anna; Denk, Christoph; Stanek, Johann; Mairinger, Severin; Filip, Thomas; Sauberer, Michael; Edelhofer, Patricia; Traxl, Alexander; Muchitsch, Viktoria E; Mereiter, Kurt; Hammerschmidt, Friedrich; Cass, Carol E; Damaraju, Vijaya L; Langer, Oliver; Kuntner, Claudia

2016-11-01

Positron emission tomography (PET) using fluorine-18 ( 18 F)-labeled 2-nitroimidazole radiotracers has proven useful for assessment of tumor oxygenation. However, the passive diffusion-driven cellular uptake of currently available radiotracers results in slow kinetics and low tumor-to-background ratios. With the aim to develop a compound that is actively transported into cells, 1-(6'-deoxy-6'-[ 18 F]fluoro-β-d-allofuranosyl)-2-nitroimidazole (β-[ 18 F]1), a putative nucleoside transporter substrate, was synthetized by nucleophilic [ 18 F]fluoride substitution of an acetyl protected labeling precursor with a tosylate leaving group (β-6) in a final radiochemical yield of 12±8% (n=10, based on [ 18 F]fluoride starting activity) in a total synthesis time of 60min with a specific activity at end of synthesis of 218±58GBq/μmol (n=10). Both radiolabeling precursor β-6 and unlabeled reference compound β-1 were prepared in multistep syntheses starting from 1,2:5,6-di-O-isopropylidene-α-d-allofuranose. In vitro experiments demonstrated an interaction of β-1 with SLC29A1 and SLC28A1/2/3 nucleoside transporter as well as hypoxia specific retention of β-[ 18 F]1 in tumor cell lines. In biodistribution studies in healthy mice β-[ 18 F]1 showed homogenous tissue distribution and excellent metabolic stability, which was unaffected by tissue oxygenation. PET studies in tumor bearing mice showed tumor-to-muscle ratios of 2.13±0.22 (n=4) at 2h after administration of β-[ 18 F]1. In ex vivo autoradiography experiments β-[ 18 F]1 distribution closely matched staining with the hypoxia marker pimonidazole. In conclusion, β-[ 18 F]1 shows potential as PET hypoxia radiotracer which merits further investigation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preliminary study on the evaluation of Langerhans cell histiocytosis using F-18-fluoro-deoxy-glucose PET/CT

Institute of Scientific and Technical Information of China (English)

Zhou Wenlan; Wu Hubing; Han Yanjiang; Wang Shaobo; Dong Ye; Wang Quanshi

2014-01-01

Background Limited number of studies have been reported regarding the utilization of F-18-fluoro-deoxy-glucose (F-18-FDG) positron emission tomography/computed tomography (F-18-FDG PET/CT) in Langerhans cell histiocytosis (LCH).The aim of this study was to assess the role of F-18-FDG PET/CT in the diagnosis and treatment of LCH.Methods Eight newly diagnosed and seven recurrent patients with LCH received F-18-FDG PET/CT scans.The diagnosis of LCH was established by pathology,multi-modality imaging,and clinical follow-up.Results F-18-FDG PET/CT was positive in 14 patients with 13 true positives and one false positive.All 45 LCH lesions were F-18-FDG avid including six small bone lesions ＜1.0 cm in diameter.The mean maximal standardized uptake value (SUVmax) was 7.13±4.91.F-18-FDG uptake showed no significant difference between newly diagnosed lesions vs recurrent lesions (SUVmax:6.50±2.97 vs.7.93±6.60,t=-0.901,P=0.376).Among 45 LCH lesions,68.9％ (31/45) were found in bones and 31.1％ (14/45) in soft tissue.The most commonly involved bones were the pelvis and vertebrae.There was no significant difference in F-18-FDG uptake between bone lesions vs.non-bone lesions (SUVmax:6.30±2.87 vs.8.97±7.58,t=1.277,P=0.221).In two patients,changes in F-18-FDG uptake on serial PET/CT scans reflected response of lesions to treatment.Conclusions The present study suggests that F-18-FDG PET/CT may be useful for diagnosis and assessing the treatment response of LCH.Because of the small sample size,further research is warranted to confirm our findings.

Impact of incidental findings on integrated 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography in patients with gastric cancer.

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Tae, Chung Hyun; Lee, Jun Haeng; Choi, Joon Young; Min, Byung-Hoon; Rhee, Poong-Lyul; Kim, Jae J

2015-03-01

Since positron emission tomography/computed tomography (PET/CT) has been introduced, many incidental findings have been identified. The aim of this study was to assess the clinical significance of incidental findings on PET/CT in patients with gastric cancer. A total of 421 patients with gastric cancer underwent PET/CT for initial staging. Incidental findings on PET/CT were classified into five categories according to clinical significance--normal variant, benign, probably benign, probably malignant, and definitely malignant. We obtained information regarding follow-up examinations, additional visits, final diagnosis of incidental findings and short-term medical costs for further evaluation. Eight hundred eighty-two incidental findings were detected in 386 (91.7%) patients. Of 274 incidental findings classified as probably benign, probably malignant or definitely malignant, 130 required one or more additional investigations. Finally, 12 (9.2%) were proved to be associated with second primary malignancy or metastasis of gastric cancer. One hundred twenty-nine additional outpatient visits and 10 additional hospitalizations were needed for evaluating the incidental findings. The treatment strategy for gastric cancer was changed in one patient. The estimated cost of additional investigations was $US283 (95% CI: $US248-$US311) per patient. Incidental findings on PET/CT were common. Although the incidental findings were suspicious of malignancy, most were benign with high costs for additional investigations. © 2015 Wiley Publishing Asia Pty Ltd.

Novel synthesis and initial preclinical evaluation of (18)F-[FDG] labeled rhodamine: a potential PET myocardial perfusion imaging agent.

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AlJammaz, Ibrahim; Al-Otaibi, Basim; AlHindas, Hussein; Okarvi, Subhani M

2015-10-01

Myocardial perfusion imaging is one of the most commonly performed investigations in nuclear medicine studies. Due to the clinical importance of [(18)F]-fluoro-2-deoxy-D-glucose ([(18)F]-FDG) and its availability in almost every PET center, a new radiofluorinated [(18)F]-FDG-rhodamine conjugate was synthesized using [(18)F]-FDG as a prosthetic group. In a convenient and simple one-step radiosynthesis, [(18)F]-FDG-rhodamine conjugate was prepared in quantitative radiochemical yields, with total synthesis time of nearly 20 min and radiochemical purity of greater than 98%, without the need for HPLC purification, which make these approaches amenable for automation. Biodistribution studies in normal rats at 60 min post-injection demonstrated a high uptake in the heart (>11% ID/g) and favorable pharmacokinetics. Additionally, [(18)F]-FDG-rhodamine showed an extraction value of 27.63%±5.12% in rat hearts. These results demonstrate that [(18)F]-FDG-rhodamine conjugate may be useful as an imaging agent for the positron emission tomography evaluation of myocardial perfusion. Copyright © 2015 Elsevier Inc. All rights reserved.

A clinical positron emission tomography facility. 2-18FDG studies: Development and results

International Nuclear Information System (INIS)

Ohlsson, Tomas.

1996-10-01

Two different types of accelerators have been used for production of ( 18 F)fluoride, and the isotope produced has been used for radiolabelling of 2-fluoro-2-deoxy-D-glucose (2- 18 FDG). A rotating PET scanner, based on two scintillation camera heads, has been developed and used for human 2- 18 FDG studies. The suitability of an energy window in the Compton region for imaging 511 keV photons in scintillation camera systems has been evaluated. A new simplified method for normalizing clinical 2- 18 FDG results has been developed and validated, using erythrocytes as a reference tissue, requiring only one blood sample in the middle of the PET scan to calculate the integrated 2- 18 FDG input function with an accuracy better than 8 percent. An investigation using 2- 18 FDG PET to monitor the effect of therapy in advanced head and neck cancer patients has been performed. We found that low initial metabolic rate of glucose (MRG) predicted a complete local response. The second PET examination gave no further information for this group. In the group of primary tumours and lymph node metastases representing a combination of high initial MRG and small decrease in MRG at he second PET examination, the outcome was unfavourable. An accurate normalization of 2- 18 FDG uptake was essential to evaluate the results of this study. 239 refs, 10 tabs

Effects of tetrahydrocannabinol on glucose uptake in the rat brain.

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Miederer, I; Uebbing, K; Röhrich, J; Maus, S; Bausbacher, N; Krauter, K; Weyer-Elberich, V; Lutz, B; Schreckenberger, M; Urban, R

2017-05-01

Δ 9 -Tetrahydrocannabinol (THC) is the psychoactive component of the plant Cannabis sativa and acts as a partial agonist at cannabinoid type 1 and type 2 receptors in the brain. The goal of this study was to assess the effect of THC on the cerebral glucose uptake in the rat brain. 21 male Sprague Dawley rats (12-13 w) were examined and received five different doses of THC ranging from 0.01 to 1 mg/kg. For data acquisition a Focus 120 small animal PET scanner was used and 24.1-28.0 MBq of [ 18 F]-fluoro-2-deoxy-d-glucose were injected. The data were acquired for 70 min and arterial blood samples were collected throughout the scan. THC, THC-OH and THC-COOH were determined at 55 min p.i. Nine volumes of interest were defined, and the cerebral glucose uptake was calculated for each brain region. Low blood THC levels of glucose uptake (6-30 %), particularly in the hypothalamus (p = 0.007), while blood THC levels > 10 ng/ml (injected dose: ≥ 0.05 mg/kg) coincided with a decreased glucose uptake (-2 to -22 %), especially in the cerebellar cortex (p = 0.008). The effective concentration in this region was estimated 2.4 ng/ml. This glucose PET study showed that stimulation of CB1 receptors by THC affects the glucose uptake in the rat brain, whereby the effect of THC is regionally different and dependent on dose - an effect that may be of relevance in behavioural studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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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

Tumour imaging by Positron Emission Tomography using fluorinase generated 5-[18F]fluoro-5-deoxyribose as a novel tracer

International Nuclear Information System (INIS)

Dall'Angelo, Sergio; Bandaranayaka, Nouchali; Windhorst, Albert D.; Vugts, Danielle J.; Born, Dion van der; Onega, Mayca; Schweiger, Lutz F.; Zanda, Matteo; O'Hagan, David

2013-01-01

Introduction: 5-[ 18 F]Fluoro-5-deoxyribose ([ 18 F]FDR) 3 was prepared as a novel monosaccharide radiotracer in a two-step synthesis using the fluorinase, a C-F bond forming enzyme, and a nucleoside hydrolase. The resulting [ 18 F]FDR 3 was then explored as a radiotracer for imaging tumours (A431 human epithelial carcinoma) by positron emission tomography in a mice model. Methods: 5-[ 18 F]Fluoro-5-deoxyribose ([ 18 F]FDR) 3, was prepared by incubating S-adenosyl-L-methionine (SAM) and [ 18 F]fluoride with the fluorinase enzyme, and then incubating the product of this reaction, [ 18 F]-5'-fluoro-5'-deoxadenosine ([ 18 F]FDA) 2, with an adenosine hydrolase to generate [ 18 F]FDR 3. The enzymes were freeze-dried and were used on demand by dissolution in buffer solution. The resulting [ 18 F]FDR 3 was then administered to four mice that had tumours induced from the A431 human epithelial carcinoma cell line. Results: The tumour (A431 human epithelial carcinoma) bearing mice were successfully imaged with [ 18 F]FDR 3. The radiotracer displayed good tumour imaging resolution. A direct comparison of the uptake and efflux of [ 18 F]FDR 3 with 2-[ 18 F]fluoro-2-deoxyglucose ([ 18 F]FDG) was made, revealing comparative tumour uptake and imaging potential over the first 10–20 min. The study revealed however that [ 18 F]FDR 3 does not accumulate in the tumour as efficiently as [ 18 F]FDG over longer time periods. Conclusions: [ 18 F]FDR 3 can be rapidly synthesised in a two enzyme protocol and used to image tumours in small animal models

False Positive 18F-FDG Uptake in Mediastinal Lymph Nodes Detected with Positron Emission Tomography in Breast Cancer: A Case Report

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Gamze Uğurluer

2013-01-01

Full Text Available Breast cancer is the most frequently diagnosed cancer among females. It is accepted that lymph node involvement with metastatic tumor and the presence of distant metastasis are the most important prognostic factors. Accurate staging is important in determining prognosis and appropriate treatment. Positron emission tomography with computed tomography detects malignancies using 2-[18F]-fluoro-2-deoxy-d-glucose (18F-FDG PET CT with high accuracy and they contribute to decisions regarding diagnosis, staging, recurrence, and treatment response. Here, we report a case of false positive metastatic mediastinal lymph nodes that were diagnosed by 18F-FDG PET CT in a 40-year-old breast cancer patient who had undergone preoperative evaluation. Right paratracheal, prevascular, aorticopulmonary, precarinal, subcarinal, hilar, and subhilar multiple conglomerated mediastinal lymph nodes were revealed in addition to left breast mass and axillary lymph nodes. Mediastinoscopy was performed with biopsy and pathology was reported as granulomatous lymphadenitis. In conclusion, any abnormal FDG accumulation in unusual lymph nodes must be evaluated carefully and confirmed histopathologically.

Positron Emission Tomography (PET) Experience with 2-[18F]Fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]FA) in the Living Human Brain of Smokers with Paranoid Schizophrenia

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BRAŠIĆ, JAMES ROBERT; CASCELLA, NICOLA; KUMAR, ANIL; ZHOU, YUN; HILTON, JOHN; RAYMONT, VANESSA; CRABB, ANDREW; GUEVARA, MARIA RITA; HORTI, ANDREW G.; WONG, DEAN FOSTER

2012-01-01

Utilizing postmortem data (Breese, et al., 2000), we hypothesized that the densities of high-affinity neuronal α4β2 nicotinic acetylcholine receptors (nAChRs) in the brain exist in a continuum from highest to lowest as follows: smokers without schizophrenia > smokers with schizophrenia > nonsmokers without schizophrenia > nonsmokers with schizophrenia. Application of the Kruskal-Wallis Test (Stata, 2003) to the postmortem data (Breese, et al., 2000) confirmed the hypothesized order in the cortex and the hippocampus and attained significance in the caudate and the thalamus. Positron emission tomography (PET) was performed for 60 minutes at 6 hours after the intravenous administration of 444 megabequerels [MBq] (12 mCi) 2-[18F]fluoro-3-(2(S)-azetidinylmethoxy)pyridine (2-[18F]FA), a radiotracer for high-affinity neuronal α4β2 nAChRs, as a bolus plus continuous infusion to 10 adults (7 men and 3 women) (6 smokers including 5 with paranoid schizophrenia and 4 nonsmokers) ranging in age from 22 to 56 years (mean 40.1, standard deviation 13.6). The thalamic nondisplaceable binding potential (BPND) was 1.32 ± 0.19 (mean ± standard deviation) for healthy control nonsmokers; 0.50 ± 0.19 for smokers with paranoid schizophrenia; and 0.51 for the single smoker without paranoid schizophrenia. The thalamic BPNDs of nonsmokers were significantly higher than those of smokers who smoked cigarettes a few hours before the scans (P = 0.0105) (StataCorp, 2003), which was likely due to occupancy of nAChRs by inhaled nicotine in smokers. Further research is needed to rule out the effects of confounding variables. PMID:22169936

Basic hydrolysis of 1, 3, 4, 6-tetra-O-acetyl-2-[18F] fluoro-D-glucose on solid phase extraction

International Nuclear Information System (INIS)

Zhang Jinming; Tian Jiahe; He Yijie; Huan Dingcai; Liu Boli

2003-01-01

A new base hydrolysis method are used for 1, 3, 4, 6-tetra-O-acetyl-2-[ 18 F] fluoro-D-glucose on solid phase extraction. The labeled intermediate is trapped on an active C-18 solid phase extraction cartridge, and hydrolyzed in cartridge with 1 mL 2 mol/L NaOH at room temperature. The results show that there are over 99% of the labeled intermediate being turned into 18 F-FDG within 2 min. It is easy to get 18 F-FDG after neutralized with phosphate buffer, purified by C-18 and Alumina cartridge. The basic hydrolysis on solid extraction is a simple method for preparation of 18 F-FDG

Effects of melatonin on 2-deoxy-[1-14C]glucose uptake within rat suprachiasmatic nucleus

International Nuclear Information System (INIS)

Cassone, V.M.; Roberts, M.H.; Moore, R.Y.

1988-01-01

Previously, we have demonstrated that metabolic activity, shown by autoradiographic determination of 2-deoxy-[1- 14 C]glucose (2-DG) uptake, within the rat hypothalamic suprachiasmatic nuclei (SCN) was inhibited by subcutaneous injection of 1 mg/kg melatonin. To determine whether this effect was specific to a particular time of day, the effects of melatonin on 2-DG uptake were studied in several hypothalamic areas, including the SCN, supraoptic nuclei (SON), lateral hypothalamic area (LHA), and anterior hypothalamic area (AHA) every 4 h throughout the circadian day. In a second experiment, the effects of different melatonin doses were studied at the time of day at which melatonin had its maximal effect to determine the dose-response relationship of melatonin-induced inhibition of SCN 2-DG uptake. The data indicate that melatonin inhibited 2-DG uptake in the SCN alone at one time of day, primarily at circadian time (CT) 6 and CT10, 2-6 h before subjective dusk, and secondarily at CT22, just before subjective dawn. This effect was dose dependent with a 50% effective dose of 1.49 +/- 2.30 micrograms/kg. The temporal and dose-response characteristics of these effects are similar to those characterizing the entraining effects of melatonin on circadian patterns of locomotion and drinking

Development & automation of a novel ["1"8F]F prosthetic group, 2-["1"8F]-fluoro-3-pyridinecarboxaldehyde, and its application to an amino(oxy)-functionalised Aβ peptide

International Nuclear Information System (INIS)

Morris, Olivia; Gregory, J.; Kadirvel, M.; Henderson, Fiona; Blykers, A.; McMahon, Adam; Taylor, Mark; Allsop, David; Allan, Stuart; Grigg, J.; Boutin, Herve; Prenant, Christian

2016-01-01

2-["1"8F]-Fluoro-3-pyridinecarboxaldehyde (["1"8F]FPCA) is a novel, water-soluble prosthetic group. It's radiochemistry has been developed and fully-automated for application in chemoselective radiolabelling of amino(oxy)-derivatised RI-OR2-TAT peptide, (Aoa-k)-RI-OR2-TAT, using a GE TRACERlab FX-FN. RI-OR2-TAT is a brain-penetrant, retro-inverso peptide that binds to amyloid species associated with Alzheimer's Disease. Radiolabelled (Aoa-k)-RI-OR2-TAT was reproducibly synthesised and the product of the reaction with FPCA has been fully characterised. In-vivo biodistribution of ["1"8F]RI-OR2-TAT has been measured in Wistar rats.

Chemical exchange-sensitive spin-lock MRI of glucose analog 3-O-methyl-d-glucose in normal and ischemic brain.

Science.gov (United States)

Jin, Tao; Mehrens, Hunter; Wang, Ping; Kim, Seong-Gi

2018-05-01

Glucose transport is important for understanding brain glucose metabolism. We studied glucose transport with a presumably non-toxic and non-metabolizable glucose analog, 3-O-methyl-d-glucose, using a chemical exchange-sensitive spin-lock MRI technique at 9.4 Tesla. 3-O-methyl-d-glucose showed comparable chemical exchange properties with d-glucose and 2-deoxy-d-glucose in phantoms, and higher and lower chemical exchange-sensitive spin-lock sensitivity than Glc and 2-deoxy-d-glucose in in vivo experiments, respectively. The changes of the spin-lattice relaxation rate in the rotating frame (Δ R 1 ρ) in normal rat brain peaked at ∼15 min after the intravenous injection of 1 g/kg 3-O-methyl-d-glucose and almost maintained a plateau for >1 h. Doses up to 4 g/kg 3-O-methyl-d-glucose were linearly correlated with Δ R 1 ρ. In rats with focal ischemic stroke, chemical exchange-sensitive spin-lock with 3-O-methyl-d-glucose injection at 1 h after stroke onset showed reduced Δ R 1 ρ in the ischemic core but higher Δ R 1 ρ in the peri-core region compared to normal tissue, which progressed into the ischemic core at 3 h after stroke onset. This suggests that the hyper-chemical exchange-sensitive spin-lock region observed at 1 h is the ischemic penumbra at-risk of infarct. In summary, 3-O-methyl-d-glucose-chemical exchange-sensitive spin-lock can be a sensitive MRI technique to probe the glucose transport in normal and ischemic brains.

A Novel Aldo-Keto Reductase, HdRed, from the Pacific Abalone Haliotis discus hannai, Which Reduces Alginate-derived 4-Deoxy-L-erythro-5-hexoseulose Uronic Acid to 2-Keto-3-deoxy-D-gluconate.

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Mochizuki, Shogo; Nishiyama, Ryuji; Inoue, Akira; Ojima, Takao

2015-12-25

Abalone feeds on brown seaweeds and digests seaweeds' alginate with alginate lyases (EC 4.2.2.3). However, it has been unclear whether the end product of alginate lyases (i.e. unsaturated monouronate-derived 4-deoxy-L-erythro-5-hexoseulose uronic acid (DEH)) is assimilated by abalone itself, because DEH cannot be metabolized via the Embden-Meyerhof pathway of animals. Under these circumstances, we recently noticed the occurrence of an NADPH-dependent reductase, which reduced DEH to 2-keto-3-deoxy-D-gluconate, in hepatopancreas extract of the pacific abalone Haliotis discus hannai. In the present study, we characterized this enzyme to some extent. The DEH reductase, named HdRed in the present study, could be purified from the acetone-dried powder of hepatopancreas by ammonium sulfate fractionation followed by conventional column chromatographies. HdRed showed a single band of ∼ 40 kDa on SDS-PAGE and reduced DEH to 2-keto-3-deoxy-D-gluconate with an optimal temperature and pH at around 50 °C and 7.0, respectively. HdRed exhibited no appreciable activity toward 28 authentic compounds, including aldehyde, aldose, ketose, α-keto-acid, uronic acid, deoxy sugar, sugar alcohol, carboxylic acid, ketone, and ester. The amino acid sequence of 371 residues of HdRed deduced from the cDNA showed 18-60% identities to those of aldo-keto reductase (AKR) superfamily enzymes, such as human aldose reductase, halophilic bacterium reductase, and sea hare norsolorinic acid (a polyketide derivative) reductase-like protein. Catalytic residues and cofactor binding residues known in AKR superfamily enzymes were fairly well conserved in HdRed. Phylogenetic analysis for HdRed and AKR superfamily enzymes indicated that HdRed is an AKR belonging to a novel family. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

A Novel Aldo-Keto Reductase, HdRed, from the Pacific Abalone Haliotis discus hannai, Which Reduces Alginate-derived 4-Deoxy-l-erythro-5-hexoseulose Uronic Acid to 2-Keto-3-deoxy-d-gluconate*

Science.gov (United States)

Mochizuki, Shogo; Nishiyama, Ryuji; Inoue, Akira; Ojima, Takao

2015-01-01

Abalone feeds on brown seaweeds and digests seaweeds' alginate with alginate lyases (EC 4.2.2.3). However, it has been unclear whether the end product of alginate lyases (i.e. unsaturated monouronate-derived 4-deoxy-l-erythro-5-hexoseulose uronic acid (DEH)) is assimilated by abalone itself, because DEH cannot be metabolized via the Embden-Meyerhof pathway of animals. Under these circumstances, we recently noticed the occurrence of an NADPH-dependent reductase, which reduced DEH to 2-keto-3-deoxy-d-gluconate, in hepatopancreas extract of the pacific abalone Haliotis discus hannai. In the present study, we characterized this enzyme to some extent. The DEH reductase, named HdRed in the present study, could be purified from the acetone-dried powder of hepatopancreas by ammonium sulfate fractionation followed by conventional column chromatographies. HdRed showed a single band of ∼40 kDa on SDS-PAGE and reduced DEH to 2-keto-3-deoxy-d-gluconate with an optimal temperature and pH at around 50 °C and 7.0, respectively. HdRed exhibited no appreciable activity toward 28 authentic compounds, including aldehyde, aldose, ketose, α-keto-acid, uronic acid, deoxy sugar, sugar alcohol, carboxylic acid, ketone, and ester. The amino acid sequence of 371 residues of HdRed deduced from the cDNA showed 18–60% identities to those of aldo-keto reductase (AKR) superfamily enzymes, such as human aldose reductase, halophilic bacterium reductase, and sea hare norsolorinic acid (a polyketide derivative) reductase-like protein. Catalytic residues and cofactor binding residues known in AKR superfamily enzymes were fairly well conserved in HdRed. Phylogenetic analysis for HdRed and AKR superfamily enzymes indicated that HdRed is an AKR belonging to a novel family. PMID:26555267

Radiosynthesis, rodent biodistribution, and metabolism of 1-deoxy-1-[18F]fluoro-d-fructose

International Nuclear Information System (INIS)

Haradahira, Terushi; Tanaka, Akihiro; Maeda, Minoru; Kanazawa, Yoko; Ichiya, Yu-Ichi; Masuda, Kouji

1995-01-01

Fluorine-18 labeled analog of d-fructose, 1-deoxy-1-[ 18 F]fluoro-d-fructose (1-[ 18 F]FDFrc), was synthesized by nucleophilic substitution of [ 18 F]fluoride ion and the effect of the fluorine substitution on its in vivo metabolism was investigated. The tissue distributions of 1-[ 18 F]FDFrc in rats and tumor bearing mice showed initial high uptake and subsequent rapid washout of the radioactivity in the principal sites of d-fructose metabolism (kidneys, liver and small intestine). The uptakes in the brain and tumor (fibrosarcoma) were the lowest and moderate, respectively, but tended to increase with time. The in vivo metabolic studies of 1-[ 18 F]FDFrc and nonradiactive 1-FDFrc in mouse brain and tumor showed that the fluorinated analog remained unmetabolized in these tissues, indicating that the substitution of fluorine at the C-1 position produces a nonmetabolizable analog of d-fructose. Thus, 1-[ 18 F]FDFrc had no features of a metabolic trapping tracer without showing any appreciable organ or tumor specific localization

2′-deoxy-5,6-dihydro-5-azacytidine—a less toxic alternative of 2′-deoxy-5-azacytidine

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Matoušová, Marika; Votruba, Ivan; Otmar, Miroslav; Tloušťová, Eva; Günterová, Jana

2011-01-01

Restoration of transcriptionally silenced genes by means of methyltransferases inhibitors plays a crucial role in the current therapy of myelodysplastic syndromes and certain types of leukemias. A comparative study of hypomethylating activities of a series of 5-azacytidine nucleosides: 5-azacytidine (AC), 2′-deoxy-5-azacytidine (DAC) and its α-anomer (α-DAC), 5,6-dihydro-5-azacytidine (DHAC), 2′-deoxy-5,6-dihydro-5-azacytidine (DHDAC, KP-1212) and its α-anomer (α-DHDAC), and of a 2-pyrimidone ribonucleoside (zebularine) was conducted. Methylation-specific PCR was employed to detect the efficiency of individual agents on cyclin-dependent kinase inhibitor 2B and thrombospondin-1 hypermethylated gene loci. Overall changes in DNA methylation level were quantified by direct estimation of 5-methyl-2′-deoxycytidine-5′-monophosphate by HPLC using digested genomic DNA. Flow cytometric analysis of cell cycle progression and apoptotic markers was used to determine cytotoxicity of the compounds. mRNA expression was measured using qRT-PCR. 2′-deoxy-5,6-dihydro-5-azacytidine was found to be less cytotoxic and more stable than 2′-deoxy-5-azacytidine at the doses that induce comparable DNA hypomethylation and gene reactivation. This makes it a valuable tool for epigenetic research and worth further investigations to elucidate its possible therapeutic potential. PMID:21566456

2-[F-18] fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) in uncommon malignancies

International Nuclear Information System (INIS)

Nair, N.; Basu, S.

2004-01-01

This is a retrospective study with an aim to evaluate the clinical role of FDG-PET imaging in changing the decision making process or management strategies in patients with various uncommon malignancies or in malignancies where there is paucity of literature regarding application of PET at present. The study population consisted of a wide variety of various uncommon malignancies who were mainly referred from the neighboring Tata Memorial Hospital with few cases from the outside centers. Patients were fasting at least for 6 hours. Sixty minutes after injection of 370 MBq FDG, patients were imaged on the dedicated BGO based GE Advance PET scanner (General Electric Medical systems, Milwaukee, WI). Images were reconstructed using the attenuation weighted Ordered Subsets Expectation Maximization (OSEM) algorithm. Axial, coronal, sagittal and 3D images were visually interpreted and foci of increased tracer uptake were considered as disease involvement. The findings were compared lesion by lesion with other imaging procedures regarding staging, treatment response evaluation and residual disease evaluation. The malignancies selected for retrospective analysis, along with the number of cases are presented. 2 cases of chordoma were evaluated of which one had primary in the cervicodorsal region and came for PET evaluation post surgery and RT. PET showed metastatic foci in left axillary node, body of sacrum and right lower neck region in addition to the persistence of disease in the primary. The other was a case of petroclival chordoma came for disease evaluation post surgery. The MRI was inconclusive regarding persistence of residual disease and postoperative changes. PET scan was normal in the case. In a solitary case of operated Dermato-fibrosarcoma, PET revealed a hypermetabolic focus at one end of scar, subsequently proven as scar recurrence of the primary. 3 cases of skin adenexal tumour were evaluated, all of whom were upstaged by PET and changed the subsequent

Validation of 123I-6-deoxy-6-iodo-D-glucose (6-DIC) as tracer for the in-vivo glucose transport

International Nuclear Information System (INIS)

Perret, P.; Ghezzi, C.; Mathieu, J.P.; Morin, C.; Vidal, M.; Comet, M.; Fagret, D.

1997-01-01

The evaluation of the glucose transport is very important clinically because alterations of this transport were described in numerous pathologies, in neurology, oncology and endocrinology. A new analog of the 123 I-labelled has been synthesized: 123 I-6-deoxy-6-iodo-D-glucose (6-DIG). Its in-vitro biological behaviour is similar to that of 3-O-methyl-D-glucose (3-OMG), the reference tracer of glucose transport. The aim of the study was to determine if it is possible to make evident by 6-DIG a variations of in-vivo glucose transport. The studies were effected on a model of homozygote mice (db/db), genetically diabetic (NIDDM), presenting a severe insulin-resistance, characterized by deficient glucose transport in response to insulin. The studies of 6-DIG biodistribution (5 nmol/mouse) with (1.5 UI/Kg) or without exogenous insulin, were conducted in diabetic mice (db/db) and in non-diabetic (db/+) control mice. The results show that the capture of 6-DIG, as well as that of glucose, increases (by 30%) in response to insulin in most of insulin-sensitive tissues in control mice. In the insulin-resistant and hyperglycemic db/db mouse, the capture of 6-DIG is not modified, no matter whether the exogenous insulin is present. In conclusion, the 6-DIG is able to make evident a lack of glucose transport in heart, diaphragm and skeletal muscle in diabetic mouse and a physiological variation of this transport in response to insulin, in the control mouse. This result should be stressed because for the first time it is possible to evidence in-vivo variations into glucose transport with a iodated molecule

Unusual presentation of metastatic carcinoma cervix with clinically silent primary identified by 18F-flouro deoxy glucose positron emission tomography/computed tomography

International Nuclear Information System (INIS)

Senthil, Raja; Mohapatra, Ranjan Kumar; Srinivas, Shripriya; Sampath, Mouleeswaran Koramadai; Sundaraiya, Sumati

2016-01-01

Carcinoma cervix is the most common gynecological malignancy among Indian women. The common symptoms at presentation include abnormal vaginal bleeding, unusual discharge from the vagina, or pain during coitus and postmenopausal bleeding. Rarely, few patients may present with distant metastases without local symptoms. We present two patients with an unusual presentation of metastatic disease without any gynecological symptoms, where 18 F-flouro deoxy glucose positron emission tomography/computed tomography helped in identifying the primary malignancy in the uterine cervix

A clinical positron emission tomography facility. 2-{sup 18}FDG studies: Development and results

Energy Technology Data Exchange (ETDEWEB)

Ohlsson, Tomas

1996-10-01

Two different types of accelerators have been used for production of ({sup 18}F)fluoride, and the isotope produced has been used for radiolabelling of 2-fluoro-2-deoxy-D-glucose (2-{sup 18}FDG). A rotating PET scanner, based on two scintillation camera heads, has been developed and used for human 2-{sup 18}FDG studies. The suitability of an energy window in the Compton region for imaging 511 keV photons in scintillation camera systems has been evaluated. A new simplified method for normalizing clinical 2-{sup 18}FDG results has been developed and validated, using erythrocytes as a reference tissue, requiring only one blood sample in the middle of the PET scan to calculate the integrated 2-{sup 18}FDG input function with an accuracy better than 8 percent. An investigation using 2-{sup 18}FDG PET to monitor the effect of therapy in advanced head and neck cancer patients has been performed. We found that low initial metabolic rate of glucose (MRG) predicted a complete local response. The second PET examination gave no further information for this group. In the group of primary tumours and lymph node metastases representing a combination of high initial MRG and small decrease in MRG at he second PET examination, the outcome was unfavourable. An accurate normalization of 2-{sup 18}FDG uptake was essential to evaluate the results of this study. 239 refs, 10 tabs.

Assessment of myocardial metabolic flexibility and work efficiency in human type 2 diabetes using 16-[18F]fluoro-4-thiapalmitate, a novel PET fatty acid tracer.

Science.gov (United States)

Mather, K J; Hutchins, G D; Perry, K; Territo, W; Chisholm, R; Acton, A; Glick-Wilson, B; Considine, R V; Moberly, S; DeGrado, T R

2016-03-15

Altered myocardial fuel selection likely underlies cardiac disease risk in diabetes, affecting oxygen demand and myocardial metabolic flexibility. We investigated myocardial fuel selection and metabolic flexibility in human type 2 diabetes mellitus (T2DM), using positron emission tomography to measure rates of myocardial fatty acid oxidation {16-[(18)F]fluoro-4-thia-palmitate (FTP)} and myocardial perfusion and total oxidation ([(11)C]acetate). Participants underwent paired studies under fasting conditions, comparing 3-h insulin + glucose euglycemic clamp conditions (120 mU·m(-2)·min(-1)) to 3-h saline infusion. Lean controls (n = 10) were compared with glycemically controlled volunteers with T2DM (n = 8). Insulin augmented heart rate, blood pressure, and stroke index in both groups (all P work efficiency was lower in T2DM (P = 0.006) and decreased in both groups with the insulin-induced increase in work and shift in fuel utilization (P = 0.01). Augmented fatty acid oxidation is present under baseline and insulin-treated conditions in T2DM, with impaired insulin-induced shifts away from fatty acid oxidation. This is accompanied by reduced work efficiency, possibly due to greater oxygen consumption with fatty acid metabolism. These observations suggest that improved fatty acid suppression, or reductions in myocardial fatty acid uptake and retention, could be therapeutic targets to improve myocardial ischemia tolerance in T2DM. Copyright © 2016 the American Physiological Society.

T-regulatory cells depletion is the main cause for enhanced antitumor immunity during radio-sensitization of tumors by 2-deoxy-D-glucose

International Nuclear Information System (INIS)

Farooque, Abdullah; Verma, Amit; Singh, Niharika; Chauhan, Sachin Kumar Singh; Jethani, Jyoti; Adhikari, J.S.; Dwarakanath, B.S.; Afrin, Farhat

2014-01-01

Regulatory T cells (Tregs) are known to have profound effects in blocking anti-tumor immunity. Therefore, Tregs are seen as a major hurdle that must be overcome in order to improve the efficacy of cancer therapy. The glycolytic inhibitor, 2-deoxy-d-glucose (2-DG) enhances radiation and chemotherapeutics induced death of many cancer cells in vitro and local tumor control in vivo, which was found to be associated with the enhanced anti-tumor immunity. Therefore, we investigated the role of Tregs in determining the tumor response to the combined treatment of 2-DG plus ionizing radiation. Ehrlich ascites tumor bearing mice were administered with a single dose of 2-DG (2 gm/Kg/b.wt) intravenously just before focal irradiation (10 Gy). Immuno-phenotyping of Tregs in secondary lymphoid organs was carried out using flow cytometry, while related cytokines were analyzed using bead array and ELISA. Further, mRNA and protein levels of transcription factors were assessed in sorted splenic CD4 + cells and CD4 + CD25 + using real time PCR and Western blot techniques. Results clearly showed depletion (TRAIL mediated apoptosis) of T regs (CD4 + CD25 + FoxP3 + CD39 + FR4 + GITR + CD127 - ), in blood, spleen, lymph node and tumor following the combined treatment. This led to the immune activation in the periphery, secondary lymphoid organs and massive infiltration of CD4 + , CD8 + and NK cells in the tumor, which correlated well with the complete response (cure; tumor free survival). Association of Treg depletion with the tumor response was further confirmed using low doses of cyclophosphamide (which depletes Tegs) and rapamycin (activator of Tregs),wherein the depletor of Tregs enhanced the efficacy of combined treatment, while Tregs enhancer compromised the efficacy. These studies unequivocally established the role of Tregs in determining the therapeutic response and can be used as a target for enhancing the efficacy of this combined treatment, besides establishing the potential of

Effect of thyrotropin-releasing hormone (TRH) on local cerebral glucose utilization, by the autoradiographic 2-deoxy [14C] glucose method, in conscious and pentobarbitalized rats

International Nuclear Information System (INIS)

Nagai, Y.; Narumi, S.; Nagawa, Y.; Sakurada, O.; Ueno, H.; Ishii, S.

1980-01-01

Effects of TRH and pentobarbital alone, and in combination, on local cerebral glucose utilization of rats were studied by the autoradiographic 2-deoxy[ 14 C] glucose method. TRH (5 mg/kg i.v.) reduced the rate of cerebral glucose utilization slightly in the whole brain. Locally, significant depression was observed in the following structures: frontal and visual cortices, hippocampus Ammon's horn and dentate gyrus, medial and lateral geniculate bodies, nucleus accumbens, caudate-putamen, substantia nigra, pontine gray matter, superior colliculus, superior olivary nucleus, vestibular nucleus, lateral lemniscus and cerebellar cortex. Pentobarbital (30 mg/kg i.v.) produced a marked and diffuse reduction in the rate of glucose utilization throughout the brain. TRH given 15 min after the administration of pentobarbital markedly shortened the pentobarbital sleeping time and caused some reversal of the depression in local cerebral glucose utilization produced by pentobarbital., These effects were almost completely abolished by pretreatment with intracerebroventricular injection of atropine methyl bromide (20 μg/rat). These results indicate that although TRH acts to cause a reduction in the rate of cerebral glucose utilization, it reverses the depression induced by pentobarbital, via a cholinergic mechanism, in a number of structures, some of which are related to monoaminergic systems and the reticulo-thalamo-cortical activating system. (author)

In situ formation of the amino sugars 1-amino-1-deoxy-fructose and 2-amino-2-deoxy-glucose under Maillard reaction conditions in the absence of ammonia.

Science.gov (United States)

Nashalian, Ossanna; Yaylayan, Varoujan A

2016-04-15

Replacing amino acids with their binary metal complexes during the Maillard reaction can initiate various processes, including the oxidative degradation of their glucose conjugates, generating 1-amino-1-deoxy-fructose and its derivatives. These reactive amino sugars are not easily accessible under Maillard reaction conditions and are only formed in the presence of ammonia. To explore the generality of this observation and to study in particular the ability of fructose to generate glucosamine, the amino acid-metal complexes were heated in aqueous solutions with three aldohexoses and two ketohexoses at 110°C for 2 h and the dry residues were analysed by ESI/qTOF/MS/MS. All the sugars generated relatively intense ions at [M+H](+) 180 (C6H14NO5); those ions originating from ketohexoses exhibited MS/MS fragmentations identical to glucosamine and those originating form aldohexoses showed ions identical to fructosamine. Furthermore, the amino sugars were found to form fructosazine, react with other sugars and undergo dehydration reactions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Stimulatory effect of the D2 antagonist sulpiride on glucose utilization in dopaminergic regions of rat brain

Energy Technology Data Exchange (ETDEWEB)

Pizzolato, G; Soncrant, T T; Larson, D M; Rapoport, S I

1987-08-01

Local cerebral glucose utilization (LCGU) was measured, using the quantitative autoradiographic (/sup 14/C)2-deoxy-D-glucose method, in 56 brain regions of 3-month-old, awake Fischer-344 rats, after intraperitoneal administration of sulpiride (SULP) 100 mg/kg. SULP, an atypical neuroleptic, is a selective antagonist of D2 dopamine receptors. LCGU was reduced in a few nondopaminergic regions at 1 h after drug administration. Thereafter, SULP progressively elevated LCGU in many other regions. At 3 h, LCGU was elevated in 23% of the regions examined, most of which are related to the CNS dopaminergic system (caudate-putamen, nucleus accumbens, olfactory tubercle, lateral habenula, median eminence, paraventricular hypothalamic nucleus). Increases of LCGU were observed also in the suprachiasmatic nucleus, lateral geniculate, and inferior olive. These effects of SULP on LCGU differ from the effects of the typical neuroleptic haloperidol, which produces widespread decreases in LCGU in the rat brain. Selective actions on different subpopulations of dopamine receptors may explain the different effects of the two neuroleptics on brain metabolism, which correspond to their different clinical and behavioral actions.

FGT-1 is a mammalian GLUT2-like facilitative glucose transporter in Caenorhabditis elegans whose malfunction induces fat accumulation in intestinal cells.

Directory of Open Access Journals (Sweden)

Shun Kitaoka

Full Text Available Caenorhabditis elegans (C. elegans is an attractive animal model for biological and biomedical research because it permits relatively easy genetic dissection of cellular pathways, including insulin/IGF-like signaling (IIS, that are conserved in mammalian cells. To explore C. elegans as a model system to study the regulation of the facilitative glucose transporter (GLUT, we have characterized the GLUT gene homologues in C. elegans: fgt-1, R09B5.11, C35A11.4, F53H8.3, F48E3.2, F13B12.2, Y61A9LA.1, K08F9.1 and Y37A1A.3. The exogenous expression of these gene products in Xenopus oocytes showed transport activity to unmetabolized glucose analogue 2-deoxy-D-glucose only in FGT-1. The FGT-1-mediated transport activity was inhibited by the specific GLUT inhibitor phloretin and exhibited a Michaelis constant (Km of 2.8 mM. Mannose, galactose, and fructose were able to inhibit FGT-1-mediated 2-deoxy-D-glucose uptake (P < 0.01, indicating that FGT-1 is also able to transport these hexose sugars. A GFP fusion protein of FGT-1 was observed only on the basolateral membrane of digestive tract epithelia in C. elegans, but not in other tissues. FGT-1::eGFP expression was observed from early embryonic stages. The knockdown or mutation of fgt-1 resulted in increased fat staining in both wild-type and daf-2 (mammalian insulin receptor homologue mutant animals. Other common phenotypes of IIS mutant animals, including dauer formation and brood size reduction, were not affected by fgt-1 knockdown in wild-type or daf-2 mutants. Our results indicated that in C. elegans, FGT-1 is mainly a mammalian GLUT2-like intestinal glucose transporter and is involved in lipid metabolism.

Single Hind Limb Burn Injury to Mice Alters NF Kappa B (NF-κB) Expression and [18F] 2-Fluoro-2-Deoxy-d-Glucose (FDG) Uptake

OpenAIRE

Carter, Edward A.; Hamrahi, Victoria; Paul, Kasie; Bonab, Ali A.; Jung, Walter; Tompkins, Ronald G.; Fischman, Alan J.

2014-01-01

Burn trauma to the extremities can produce marked systemic effects in mice1, 6, 7. Burn injury to the dorsal surface of mice is also associated with changes in glucose metabolism (18FDG uptake) by brown adipose tissue (BAT) and NF-κB activity in a number of tissues including skeletal muscle. This study examined the effect of a single hindlimb burn in mice on 18FDG uptake by in vivo, NF-κB activity in vivo, and blood flow determined by laser Doppler techniques. Male mice NF-κB luciferase repor...

A review of metabolism of labeled glucoses for use in measuring glucose recycling

International Nuclear Information System (INIS)

Russell, R.W.; Young, J.W.

1990-01-01

The fate of tritium from each carbon of D-glucose and the metabolism of L-glucose and 2-deoxy-D-glucose are known. Differences in metabolism of labeled glucoses can be used to quantify physical and chemical recycling of glucose. Only physical recycling is measured by [1- 3 H]-L-glucose, whereas [U- 14 C]-D-glucose measures total recycling. The difference between [1- 3 H]-L-glucose and [U- 14 C]-D-glucose, therefore, is chemical recycling. Recycling from extracellular binding sites and hepatic glucose 6-phosphate can be measured by difference between [1,2- 3 H]-2-deoxy-D-glucose and [1- 3 H]-L-glucose, and the difference in irreversible loss of the two will measure extrahepatic uptake of D-glucose. Recycling via Cori-alanine cycle plus CO 2 is the difference in irreversible loss measured by using [6- 3 H]-glucose and [U- 14 C]-D-glucose. Recycling via the hexose monophosphate pathway can be determined by difference in irreversible loss between [1- 3 H]-D-glucose and [6- 3 H]-D-glucose. Recycling via CO 2 and glycerol must be measured directly with [U- 14 C]glucose, bicarbonate, and glycerol. Recycling via hepatic glycogen can be estimated by subtracting all other measured chemical recycling from total chemical recycling. This review describes means to quantify glucose recycling in vivo, enabling studies of mechanisms for conservation and utilization of glucose. 54 references

Estimation of absorbed dose for 2-[F-18]fluoro-2-deoxy-d- glucose using whole-body positron emission tomography and magnetic resonance imaging

International Nuclear Information System (INIS)

Deloar, H.M.; Fujiwara, Takehiko; Shidahara, Miho; Nakamura, Takashi; Watabe, Hiroshi; Narita, Yuichiro; Itoh, Masatoshi; Miyake, Masayasu; Watanuki, Shoichi

1998-01-01

The purpose of this study was to measure the cumulated activity and absorbed dose in organs after i.v. administration of 18 F-FDG using whole-body PET and MRI. Whole-body dynamic emission scans for 18 F-FDG were performed in six normal volunteers after transmission scans. The total activity of a source organ was obtained from the activity concentration of the organ measured by whole-body PET and the volume of that organ measured by whole-body T1-weighted MRI. The cumulated activity of each source organ was calculated from the time-activity curve. Absorbed doses to the individuals were estimated by the MIRD (medical internal radiation dosimetry) method. Another calculation of cumulated activities and absorbed doses was performed using the organ volumes from the MIRD phantom and the ''Japanese reference man'' to investigate the discrepancy of actual individual results against the phantom results. The cumulated activities of 18 source organs were calculated, and absorbed doses of 27 target organs estimated. Among the target organs, bladder wall, brain and kidney received the highest doses for the above three sets of organ volumes. Using measured individual organ volumes, the average absorbed doses for those organs were found to be 3.1 x 10 -1 , 3.7 x 10 -2 and 2.8 x 10 -2 mGy/MBq, respectively. The mean effective doses in this study for individuals of average body weight (64.5 kg) and the MIRD phantom of 70 kg were the same, i.e. 2.9 x 10 -2 mSv/MBq, while for the Japanese reference man of 60 kg the effective dose was 2.1 x 10 -2 mSv/MBq. The results for measured organ volumes derived from MRI were comparable to those obtained for organ volumes from the MIRD phantom. Although this study considered 18 F-FDG, combined use of whole-body PET and MRI might be quite effective for improving the accuracy of estimations of the cumulated activity and absorbed dose of positron-labelled radiopharmaceuticals.(orig./MG) (orig.)

Evaluation of Schmorl's nodes using F-18 FDG PET/CT

International Nuclear Information System (INIS)

Lin, C.-Y.; Chen, H.-Y.; Ding, H.-J.; Chen, Y.-K.; Kao, C.-H.

2012-01-01

Aim: To evaluate the image findings of Schmorl's nodes on combined 2-[ 18 F]-fluoro-2-deoxy-D-glucose positron-emission tomography/computed tomography (FDG PET/CT). Materials and methods: Twelve patients who were diagnosed with Schmorl's nodes and had undergone magnetic resonance imaging (MRI) and FDG PET/CT were retrospectively recruited for this study. The period between the MRI and the FDG PET/CT examinations was within 1 week. The demographic data and clinical history were reviewed. The relationship between MRI findings and the values of maximum standardized uptake value (SUVmax) on FDG PET/CT was analysed. Results: The mean values of early and delayed SUVmax of Schmorl's nodes without MRI enhancement were 1.14 ± 0.28 and 1.09 ± 0.32. The mean values of early and delayed SUVmax of Schmorl's nodes with MRI enhancement were 1.73 ± 0.49 and 1.75 ± 0.54. There were significant differences in the early and delayed SUVmax between Schmorl's nodes with and without perifocal enhancement on MRI with Wilcoxon's rank-sum test (p = 0.012; p = 0.006). There was a trend of positive correlation, although not statistically significant, between delayed SUVmax on FDG PET/CT and age in Schmorl's nodes with Spearman’s rank correlation (B = 0.86, p = 0.056). Conclusions: Schmorl's nodes demonstrated low to moderate uptake on FDG PET/CT images. Schmorl's nodes with perifocal enhancement on MRI result in higher FDG uptake. The possibility of false positives caused by Schmorl's nodes should be considered when interpreting FDG PET/CT images of bone metastases, especially in the aging population.

Comparisons of [18F]-1-deoxy-1-fluoro-scyllo-inositol with [18F]-FDG for PET imaging of inflammation, breast and brain cancer xenografts in athymic mice

International Nuclear Information System (INIS)

McLarty, Kristin; Moran, Matthew D.; Scollard, Deborah A.; Chan, Conrad; Sabha, Nesrin; Mukherjee, Joydeep; Guha, Abhijit; McLaurin, JoAnne; Nitz, Mark; Houle, Sylvain; Wilson, Alan A.; Reilly, Raymond M.; Vasdev, Neil

2011-01-01

Introduction: The aim of the study was to evaluate the uptake of [ 18 F]-1-deoxy-1-fluoro-scyllo-inositol ([ 18 F]-scyllo-inositol) in human breast cancer (BC) and glioma xenografts, as well as in inflammatory tissue, in immunocompromised mice. Studies of [ 18 F]-2-fluoro-2-deoxy-D-glucose ([ 18 F]-FDG) under the same conditions were also performed. Methods: Radiosynthesis of [ 18 F]-scyllo-inositol was automated using a commercial synthesis module. Tumour, inflammation and normal tissue uptakes were evaluated by biodistribution studies and positron emission tomography (PET) imaging using [ 18 F]-scyllo-inositol and [ 18 F]-FDG in mice bearing subcutaneous MDA-MB-231, MCF-7 and MDA-MB-361 human BC xenografts, intracranial U-87 MG glioma xenografts and turpentine-induced inflammation. Results: The radiosynthesis of [ 18 F]-scyllo-inositol was automated with good radiochemical yields (24.6%±3.3%, uncorrected for decay, 65±2 min, n=5) and high specific activities (≥195 GBq/μmol at end of synthesis). Uptake of [ 18 F]-scyllo-inositol was greatest in MDA-MB-231 BC tumours and was comparable to that of [ 18 F]-FDG (4.6±0.5 vs. 5.5±2.1 %ID/g, respectively; P=.40), but was marginally lower in MDA-MB-361 and MCF-7 xenografts. Uptake of [ 18 F]-scyllo-inositol in inflammation was lower than [ 18 F]-FDG. While uptake of [ 18 F]-scyllo-inositol in intracranial U-87 MG xenografts was significantly lower than [ 18 F]-FDG, the tumour-to-brain ratio was significantly higher (10.6±2.5 vs. 2.1±0.6; P=.001). Conclusions: Consistent with biodistribution studies, uptake of [ 18 F]-scyllo-inositol was successfully visualized by PET imaging in human BC and glioma xenografts, with lower accumulation in inflammatory tissue than [ 18 F]-FDG. The tumour-to-brain ratio of [ 18 F]-scyllo-inositol was also significantly higher than that of [ 18 F]-FDG for visualizing intracranial glioma xenografts in NOD SCID mice, giving a better contrast. -- Graphical Abstract: Display Omitted

Cerebral (18)FluoroDeoxy-Glucose Positron Emission Tomography in paediatric anti N-methyl-D-aspartate receptor encephalitis: A case series.

Science.gov (United States)

Lagarde, Stanislas; Lepine, Anne; Caietta, Emilie; Pelletier, Florence; Boucraut, José; Chabrol, Brigitte; Milh, Mathieu; Guedj, Eric

2016-05-01

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a frequent and severe cause of encephalitis in children with potential efficient treatment (immunotherapy). Suggestive clinical features are behavioural troubles, seizures and movement disorders. Prompt diagnosis and treatment initiation are needed to guarantee favourable outcome. Nevertheless, diagnosis may be challenging because of the classical ancillary test (magnetic resonance imaging (MRI), electroencephalogram, standard cerebro-spinal fluid analysis) have limited sensitivity. Currently, immunological analyses are needed for the diagnostic confirmation. In adult patients, some studies suggested a potential role of cerebral (18)FluoroDeoxy-Glucose Positron Emission Tomography (FDG-PET) in the evaluation of anti-NMDAR encephalitis. Nevertheless, almost no data exist in paediatric population. We report retrospectively clinical, ancillary tests and cerebral FDG-PET data in 6 young patients (median age=10.5 years, 4 girls) with immunologically confirmed anti-NMDAR encephalitis. Our patients presented classical clinical features of anti-NMDAR encephalitis with severe course (notably four patients had normal MRI). Our series shows the feasibility and the good sensitivity of cerebral FDG-PET (6/6 patients with brain metabolism alteration) in paediatric population. We report some particular features in this population: extensive, symmetric cortical hypometabolism especially in posterior areas; asymmetric anterior focus of hypermetabolism; and basal ganglia hypermetabolism. We found also a good correlation between the clinical severity and the cerebral metabolism changes. Moreover, serial cerebral FDG-PET showed parallel brain metabolism and clinical improvement. Our study reveals the existence of specific patterns of brain metabolism alteration in anti-NMDAR encephalitis in paediatric population. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Positron emission tomography in the management of cervix cancer patients

International Nuclear Information System (INIS)

Bonardel, G.; Gontier, E.; Soret, M.; Dechaud, C.; Fayolle, M.; Foehrenbach, H.; Chargari, C.; Bauduceau, O.

2009-01-01

Since its introduction in clinical practice in the 1990 s, positron emission tomography (PET), usually with 18 F-fluoro-2-deoxy-D-glucose ( 18 F-F.D.G.), has become an important imaging modality in patients with cancer. For cervix carcinoma, F.D.G.-PET is significantly more accurate than computed tomography (CT) and is recommended for loco-regional lymph node and extra pelvic staging. The metabolic dimension of the technique provides additional prognostic information. Ongoing studies now concentrate on more advanced clinical applications, such as the planning of radiotherapy, the response evaluation after the induction of therapy, the early detection of recurrence. Technical innovations, such as PET cameras with better spatial resolution and hybrid positron emission tomography/computed tomography (PET-CT), available now on the whole territory, provide both anatomic and metabolic information in the same procedure. From the point of view of biological metabolism, new radiopharmaceutical probes are being developed. Those hold promise for future refinements in this field. This article reviews the current applications of F.D.G.-PET in patients with cervix cancer. (authors)

Positron emission tomography in the management of cervix cancer patients; Tomographie par emission de positons dans la prise en charge des cancers du col de l'uterus

Energy Technology Data Exchange (ETDEWEB)

Bonardel, G.; Gontier, E.; Soret, M.; Dechaud, C.; Fayolle, M.; Foehrenbach, H. [Hopital d' Instruction des Armees du Val-de-Grace, Service de Medecine Nucleaire, 75 - Paris (France); Chargari, C.; Bauduceau, O. [Hopital d' Instruction des Armees du Val-de-Grace, Service de Radiotherapie, 75 - Paris (France)

2009-10-15

Since its introduction in clinical practice in the 1990 s, positron emission tomography (PET), usually with {sup 18}F-fluoro-2-deoxy-D-glucose ({sup 18}F-F.D.G.), has become an important imaging modality in patients with cancer. For cervix carcinoma, F.D.G.-PET is significantly more accurate than computed tomography (CT) and is recommended for loco-regional lymph node and extra pelvic staging. The metabolic dimension of the technique provides additional prognostic information. Ongoing studies now concentrate on more advanced clinical applications, such as the planning of radiotherapy, the response evaluation after the induction of therapy, the early detection of recurrence. Technical innovations, such as PET cameras with better spatial resolution and hybrid positron emission tomography/computed tomography (PET-CT), available now on the whole territory, provide both anatomic and metabolic information in the same procedure. From the point of view of biological metabolism, new radiopharmaceutical probes are being developed. Those hold promise for future refinements in this field. This article reviews the current applications of F.D.G.-PET in patients with cervix cancer. (authors)

Effect of ginseng pretreatment on cerebral glucose metabolism in ischaemic rats using animal positron emission tomography (PET) and [18F]-FDG

Energy Technology Data Exchange (ETDEWEB)

Rye, Choi Seok; Magata, Y.; Saji, H.; Tajima, K.; Kitano, H.; Konishi, J.; Yokoyama, A. [Department of Radiopharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-01 (Japan)

1997-07-01

To investigate the effect of ginseng on damaged brain activity, we evaluated the cerebral metabolic rate of glucose (CMRglc) as a functional index in post-ischaemic rats and compared the results with those obtained after the administration of a ginseng extract. CMRglc was measured using high resolution animal positron emission tomography with {sup 18}F-2-fluoro-2-deoxy-D-glucose ({sup 18}F-FDG). The rats subjected to a 30-min occlusion showed a significant reduction of k3, the rate constant for phosphorylation of {sup 18}F-FDG by hexokinase, compared with the normal value. The ginseng pretreatment prevented the reduction in k3 and CMRglc caused by ischaemia. Although further investigation is needed to elucidate the mechanism of action, ginseng may be useful for prevention and treatment of ischaemia. © 1997 John Wiley & Sons, Ltd.

Selective inhibitory effects of (S)-9-(3-hydroxy-2-phosphonyl-methoxypropyl)adenine and 1-(2'-deoxy-2'-fluoro-ß-D-arabinofuranosyl)-5-iodouracil on seal herpesvirus (Phocid herpesvirus 1) infection in vitro.

NARCIS (Netherlands)

A.D.M.E. Osterhaus (Albert); J. Groen (Jan); E. de Clercq

1987-01-01

textabstractFrom a selection of 25 antiviral compounds with specific anti-herpes activity or broad-spectrum antiviral properties, two compounds, namely (S)-9-(3-hydroxy-2-phosphonyl-methoxypropyl)adenine and 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodouracil, appeared particularly effective

The synthesis of the 2H, 3H, and 14C-isotopomers of 2'-deoxy-2',2'-difluorocytidine hydrochloride, an anti-tumor compound

International Nuclear Information System (INIS)

Wheeler, W.J.; Mabry, T.E.; Jones, C.D.

1991-01-01

The 2 H, 3 H, and 14 C-isotopomers of 2'-deoxy-2', 2'-difluorocytidine hydrochloride (gemcitabine hydrochloride) have been synthesized in two radiochemical steps from the reaction of bis-trimethylsilylcytosine-[2- 14 C] and 3,5-O-bis-benzoyl-1-O-methanesulfonyl-2-deoxy-2,2-difluororibose. A mixture of anomers of 3',5'-dibenzoyl-2'-deoxy-2',2'-difluorocytidine or its 14 C-isotopomer were obtained which were readily separated by crystallization from ethyl acetate. Deprotection using methanolic ammonia yielded the target compound. The 2 H and 3 H-isotopomers were prepared by deuterium (or tritium) gas hydrogenolysis of 5-iodo-2'-deoxy-2',2'-difluorocytidine. (author)

The integration of 18-fluoro-deoxy-glucose positron emission tomography and endoscopic ultrasound in the treatment-planning process for esophageal carcinoma

International Nuclear Information System (INIS)

Konski, Andre; Doss, Mohan; Milestone, Barton; Haluszka, Oleh; Hanlon, Alexandra; Freedman, Gary; Adler, Lee

2005-01-01

Purpose: Accurate delineation of the gross tumor volume (GTV) is important in radiation therapy treatment planning. We evaluated the impact of PET and endoscopic ultrasound (EUS) compared with CT simulation in the planning of radiation fields for patients with esophageal carcinoma. Material and methods: Twenty-five patients presenting with esophageal carcinoma for radiation therapy underwent PET scans in the treatment position after conventional CT simulation. Patients underwent PET/CT scanning after being injected with 10 to 20 mCi of [F-18]-2-deoxy-2-fluro-D-glucose. The length of the abnormality seen on the CT portion of the PET/CT scan vs. the PET scan alone was determined independently by 2 separate investigators. The length of the GTV and detection of regional adenopathy by PET was also correlated with EUS in 18 patients. Of the 18 patients who had EUS, 2 had T2 tumors and 16 had T3 tumors. Eighteen patients had adenocarcinoma and 7 had squamous cell carcinoma. Nine tumors were located at the gastroesophageal junction, 8 at the lower esophagus, 7 in the middle esophagus, and 1 in the cervical esophagus. The PET scans were reviewed to determine the length of the abnormality by use of a standard uptake value (SUV) of 2.5 to delineate the tumor extent. Results: The mean length of the cancer was 5.4 cm (95% CI 4.4-6.4 cm) as determined by PET scan, 6.77 cm (95% CI, 5.6-7.9 cm) as determined by CT scan, and 5.1 cm (95% CI, 4.0-6.1 cm) for the 22 patients who had endoscopy. The length of the tumors was significantly longer as measured by CT scans compared with PET scans (p = 0.0063). EUS detected significantly more patients with periesophageal and celiac lymphadenopathy compared to PET and CT. The SUV of the esophageal tumors was higher in patients with peri-esophageal lymphadenopathy identified on PET scans. Conclusion: Endoscopic ultrasound and PET scans can add additional information to aid the radiation oncologist's ability to precisely identify the GTV in

Single Hind Limb Burn Injury to Mice Alters NF Kappa B (NF-κB) Expression and [18F] 2-Fluoro-2-Deoxy-d-Glucose (FDG) Uptake

Science.gov (United States)

Carter, Edward A.; Hamrahi, Victoria; Paul, Kasie; Bonab, Ali A.; Jung, Walter; Tompkins, Ronald G.; Fischman, Alan J.

2014-01-01

Burn trauma to the extremities can produce marked systemic effects in mice1, 6, 7. Burn injury to the dorsal surface of mice is also associated with changes in glucose metabolism (18FDG uptake) by brown adipose tissue (BAT) and NF-κB activity in a number of tissues including skeletal muscle. This study examined the effect of a single hindlimb burn in mice on 18FDG uptake by in vivo, NF-κB activity in vivo, and blood flow determined by laser Doppler techniques. Male mice NF-κB luciferase reporter mice (28 grams- 30 grams, male) were anesthetized, both legs were shaven, and the right leg was subjected to scald injury by immersion in 90°C water for 5 seconds. Sham treated animals were used as controls. Each burned and sham mouse was resuscitated with saline (2 ml, IP). The individual animals were placed in wire bottom cages with no food and free access to water. 24 hrs later, the animals were imaged with Laser Doppler for measurements of blood flow in the hind limb. The animals were then injected unanesthetized with 50 µCi of FDG or luciferin (1.0 mg), I.V. via tail vein. Five minutes after luciferin injection, NF-kB mice were studied by bioluminescence imaging with a CCD camera. One hour after 18FDG injection the animals were euthanized with carbon dioxide overdose and 18FDG biodistribution was measured. Tissues were also analyzed for NF-κB luciferase activity. The scalding procedure used here produced a full thickness burn injury to the leg with sharp margins. 18FDG uptake by the burned leg was lower than in the contralateral limb. Similarly luciferase activity and blood flow in the burned leg were lower than in the contralateral leg. 18FDG uptake by BAT and heart was increased, while brain was decreased. In conclusion, the present study suggests that burn injury to a single leg reduced 18FDG uptake by skeletal muscle but increased 18FDG uptake by BAT. The injury to the leg reduced NF-κB expression as compared to the contralateral leg and the uninjured

Temperature dependence of the heat capacities in the solid state of 18 mono-, di-, and poly-saccharides

International Nuclear Information System (INIS)

Hernandez-Segura, Gerardo O.; Campos, Myriam; Costas, Miguel; Torres, Luis A.

2009-01-01

The temperature dependence of the heat capacities in solid state C p (T) of 18 mono-, di-, and poly-saccharides has been determined using a power-compensation differential scanning calorimeter. The saccharides were α-D-xylose, D-ribose, 2-deoxy-D-ribose, methyl-β-D-ribose, α-D-glucose, 2-deoxy-D-glucose, α-D-mannose, β-D-fructose, α-D-galactose, methyl-α-D-glucose, sucrose, maltose monohydrate, α-lactose monohydrate, cellobiose, maltotriose, N-acetyl-D-glucosamine, α-cyclodextrin, and β-cyclodextrin. The measurements were carried out at atmospheric pressure and from T = (288.15 to 358.15) K for 15 saccharides and from T = (288.15 to 328.15) K for D-ribose, 2-deoxy-D-ribose, and methyl-β-D-ribose. The present results are compared against literature values both at single temperatures, where most of the data are available, and throughout a range of temperatures, i.e., for C p (T). The predictions of a recently published correlation for organic solids are briefly discussed. By grouping saccharides in subsets, our present results can be used to compare amongst saccharide isomers and to assess the effect of different chemical groups and molecular size

15-Deoxy-delta12,14-prostaglandin J2, a neuroprotectant or a neurotoxicant?

International Nuclear Information System (INIS)

Koh, Seong-Ho; Jung, Boo; Song, Chi Won; Kim, Youngchul; Kim, Yong Soon; Kim, Seung Hyun

2005-01-01

15-Deoxy-delta12,14-prostaglandin J2 (15d-PGJ2) is a potent ligand for peroxisome proliferators-activated receptor γ (PPARγ). However, its various effects independent of PPARγ have recently been observed. The effect of 15d-PGJ2 on neuronal cells is still controversial. We investigated its effect on neuronal cells (N18D3 cells). When N18D3 cells were treated with 15d-PGJ2, the viability was not changed up to 8 μM, but decreased at higher than 8 μM. The expressions of survival signals, such as p85a phosphatidylinositol 3-kinase, phospho-Akt, and phospho-glycogen synthase kinase-3 beta (Ser-9), slightly increased up to 8 μM, however, decreased at higher than 8 μM. The levels of free radicals and membrane lipid peroxidation and the expression of c-Jun N-terminal Kinase increased in a dose-dependent manner, especially at higher than 8 μM. However, the expressions of death signals, such as cytosolic cytochrome c, activated caspase-3, and cleaved poly(ADP-ribose) polymerase, decreased up to 8 μM, however, increased at higher than 8 μM. In the study to evaluate whether low dose of 15d-PGJ2, up to 8 μM, had protective effect on oxidative stress-injured N18D3 cells, compared to the cells treated with only 100 μM H 2 O 2 , the pretreatment with 8 μM 15d-PGJ2 increased the viability and the expressions of the survival signals, but decreased them of the death signals. These results indicate that 15d-PGJ2 could be a neuroprotectant or a neurotoxicant, depending on its concentration. Therefore, some specific optimum dose of 15d-PGJ2 may be a new potential therapeutic candidate for oxidative stress-injury model of neurodegenerative diseases

Metabolism of 2-deoxyglyconic acid in plants and bakers yeast

International Nuclear Information System (INIS)

Gakhokidze, R.A.; Beriashvili, L.T.; Chigvinadze, T.D.

1996-01-01

During photosynthesis in Phaseolus vulgaris haricot bean and Zea mays leaves, assimilated carbon 14 CO 2 is rapidly incorporated into aldonic acids including 2-deoxygluconic acid whose radioactivity was relatively high. In these plants, radioactive carbon of 2-deoxy-D-gluconic acid prepared from 1-6 14 C-D-glucose is actively involved in the formation of sugars, organic acids, and amino acids. In baking yeast Saccharomyces cerevisiae, the rate of respiration-dependent oxidation of 2-deoxy-D-gluconic acid differs versus the rate of D-glucose oxidation [ru

Comparisons of [{sup 18}F]-1-deoxy-1-fluoro-scyllo-inositol with [{sup 18}F]-FDG for PET imaging of inflammation, breast and brain cancer xenografts in athymic mice

Energy Technology Data Exchange (ETDEWEB)

McLarty, Kristin; Moran, Matthew D. [Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8 (Canada); PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Scollard, Deborah A.; Chan, Conrad [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Sabha, Nesrin; Mukherjee, Joydeep; Guha, Abhijit [Arthur and Sonia Labatt Brain Tumour Research Centre, Hospital for Sick Children, University of Toronto, ON, M5G 1X8 (Canada); McLaurin, JoAnne [Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, M5S 3H2 (Canada); Nitz, Mark [Department of Chemistry, University of Toronto, Toronto, ON, M5S 3H6 (Canada); Houle, Sylvain; Wilson, Alan A. [Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8 (Canada); PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada); Reilly, Raymond M., E-mail: raymond.reilly@utoronto.ca [Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Toronto General Research Institute, University Health Network, Toronto, ON, M5G 2M9 (Canada); Department of Medical Imaging, University of Toronto, Toronto, ON, M5S 3M2 (Canada); Vasdev, Neil, E-mail: neil.vasdev@utoronto.ca [Department of Psychiatry, University of Toronto, Toronto, ON, M5T 1R8 (Canada); PET Centre, Centre for Addiction and Mental Health, Toronto, ON, M5T 1R8 (Canada)

2011-10-15

Introduction: The aim of the study was to evaluate the uptake of [{sup 18}F]-1-deoxy-1-fluoro-scyllo-inositol ([{sup 18}F]-scyllo-inositol) in human breast cancer (BC) and glioma xenografts, as well as in inflammatory tissue, in immunocompromised mice. Studies of [{sup 18}F]-2-fluoro-2-deoxy-D-glucose ([{sup 18}F]-FDG) under the same conditions were also performed. Methods: Radiosynthesis of [{sup 18}F]-scyllo-inositol was automated using a commercial synthesis module. Tumour, inflammation and normal tissue uptakes were evaluated by biodistribution studies and positron emission tomography (PET) imaging using [{sup 18}F]-scyllo-inositol and [{sup 18}F]-FDG in mice bearing subcutaneous MDA-MB-231, MCF-7 and MDA-MB-361 human BC xenografts, intracranial U-87 MG glioma xenografts and turpentine-induced inflammation. Results: The radiosynthesis of [{sup 18}F]-scyllo-inositol was automated with good radiochemical yields (24.6%{+-}3.3%, uncorrected for decay, 65{+-}2 min, n=5) and high specific activities ({>=}195 GBq/{mu}mol at end of synthesis). Uptake of [{sup 18}F]-scyllo-inositol was greatest in MDA-MB-231 BC tumours and was comparable to that of [{sup 18}F]-FDG (4.6{+-}0.5 vs. 5.5{+-}2.1 %ID/g, respectively; P=.40), but was marginally lower in MDA-MB-361 and MCF-7 xenografts. Uptake of [{sup 18}F]-scyllo-inositol in inflammation was lower than [{sup 18}F]-FDG. While uptake of [{sup 18}F]-scyllo-inositol in intracranial U-87 MG xenografts was significantly lower than [{sup 18}F]-FDG, the tumour-to-brain ratio was significantly higher (10.6{+-}2.5 vs. 2.1{+-}0.6; P=.001). Conclusions: Consistent with biodistribution studies, uptake of [{sup 18}F]-scyllo-inositol was successfully visualized by PET imaging in human BC and glioma xenografts, with lower accumulation in inflammatory tissue than [{sup 18}F]-FDG. The tumour-to-brain ratio of [{sup 18}F]-scyllo-inositol was also significantly higher than that of [{sup 18}F]-FDG for visualizing intracranial glioma xenografts in

Are dual-phase 18F-FDG PET scans necessary in nasopharyngeal carcinoma to assess the primary tumour and loco-regional nodes?

International Nuclear Information System (INIS)

Yen, Tzu-Chen; Chang, Yu-Chen; Chan, Sheng-Chieh; Lin, Kun-Ju; Chang, Joseph Tung-Chieh; Hsu, Ching-Han; Lin, Wuu-Jyh; Fu, Ying-Kai; Ng, Shu-Hang

2005-01-01

This prospective study aimed to investigate the efficacy of dual-phase positron emission tomography (PET) in evaluating the loco-regional status of nasopharyngeal carcinoma (NPC). Eighty-four patients with newly diagnosed NPC and a fasting serum glucose level of 18 F]fluoro-2-deoxy-D-glucose ( 18 F-FDG) PET studies (at 40 min and 3 h after injection of 370 MBq 18 F-FDG) and head and neck magnetic resonance imaging (MRI) were performed within 1 week. Diagnostic criteria for NPC comprised the histopathological findings, the joint judgments of the research team and the post-treatment outcome. Each lesion's maximum standardised uptake value (SUV) and retention index were obtained. SUV data were evaluated using a paired test. Receiver operating characteristic curves and calculation of the area under the curve (AUC) determined the discriminative power. 18 F-FDG PET was significantly superior to MRI in identifying lower neck NPC nodal metastasis (AUC: 1 vs 0. 972, P=0.046) and overall loco-regional metastases (AUC: 0.985 vs 0.958, P=0.036). However, 18 F-FDG PET was similar to MRI in detecting primary tumour, as well as retropharyngeal, upper neck and supraclavicular nodal metastases. There was no significant difference between early phase (40 min) and delayed phase (3 h) 18 F-FDG PET in the detection of primary tumours (accuracy: 100% vs 100%) or loco-regional nodal metastasis (AUC: 0.984 vs 0.985, P=0.834). 18 F-FDG PET is superior to MRI in identifying lower neck nodal metastasis of NPC. Additional 3-h 18 F-FDG PET contributes no further information in the detection of primary tumours or loco-regional metastatic nodes in untreated NPC patients. (orig.)

(18)F-FDG uptake predicts diagnostic yield of transbronchial biopsy in peripheral lung cancer.

Science.gov (United States)

Umeda, Yukihiro; Demura, Yoshiki; Anzai, Masaki; Matsuoka, Hiroki; Araya, Tomoyuki; Nishitsuji, Masaru; Nishi, Koichi; Tsuchida, Tatsuro; Sumida, Yasuyuki; Morikawa, Miwa; Ameshima, Shingo; Ishizaki, Takeshi; Kasahara, Kazuo; Ishizuka, Tamotsu

2014-07-01

Recent advances in endobronchial ultrasonography with a guide sheath (EBUS-GS) have enabled better visualization of distal airways, while virtual bronchoscopic navigation (VBN) has been shown useful as a guide to navigate the bronchoscope. However, indications for utilizing VBN and EBUS-GS are not always clear. To clarify indications for a bronchoscopic examination using VBN and EBUS-GS, we evaluated factors that predict the diagnostic yield of a transbronchial biopsy (TBB) procedure for peripheral lung cancer (PLC) lesions. We retrospectively reviewed the charts of 194 patients with 201 PLC lesions (≤3cm mean diameter), and analyzed the association of diagnostic yield of TBB with [(18)F]-fluoro-2-deoxy-d-glucose ((18)F-FDG) positron emission tomography and chest computed tomography (CT) findings. The diagnostic yield of TBB using VBN and EBUS-GS was 66.7%. High maximum standardized uptake value (SUVmax), positive bronchus sign, and ground-glass opacity component shown on CT were all significant predictors of diagnostic yield, while multivariate analysis showed only high (18)F-FDG uptake (SUVmax ≥2.8) and positive bronchus sign as significant predictors. Diagnostic yield was higher for PLC lesions with high (18)F-FDG uptake (SUVmax ≥2.8) and positive bronchus sign (84.6%) than for those with SUVmax PLC lesions. (18)F-FDG uptake and bronchus sign may indicate for the accurate application of bronchoscopy with those modalities for diagnosing PLC. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Influence of free fatty acids on glucose uptake in prostate cancer cells

DEFF Research Database (Denmark)

Andersen, Kim Francis; Divilov, Vadim; Sevak, Kuntalkumar

2014-01-01

The study focuses on the interaction between glucose and free fatty acids (FFA) in malignant human prostate cancer cell lines by an in vitro observation of uptake of fluoro-2-deoxy-d-glucose (FDG) and acetate.......The study focuses on the interaction between glucose and free fatty acids (FFA) in malignant human prostate cancer cell lines by an in vitro observation of uptake of fluoro-2-deoxy-d-glucose (FDG) and acetate....

Quantitative dynamic ¹⁸FDG-PET and tracer kinetic analysis of soft tissue sarcomas.

Science.gov (United States)

Rusten, Espen; Rødal, Jan; Revheim, Mona E; Skretting, Arne; Bruland, Oyvind S; Malinen, Eirik

2013-08-01

To study soft tissue sarcomas using dynamic positron emission tomography (PET) with the glucose analog tracer [(18)F]fluoro-2-deoxy-D-glucose ((18)FDG), to investigate correlations between derived PET image parameters and clinical characteristics, and to discuss implications of dynamic PET acquisition (D-PET). D-PET images of 11 patients with soft tissue sarcomas were analyzed voxel-by-voxel using a compartment tracer kinetic model providing estimates of transfer rates between the vascular, non-metabolized, and metabolized compartments. Furthermore, standard uptake values (SUVs) in the early (2 min p.i.; SUVE) and late (45 min p.i.; SUVL) phases of the PET acquisition were obtained. The derived transfer rates K1, k2 and k3, along with the metabolic rate of (18)FDG (MRFDG) and the vascular fraction νp, was fused with the computed tomography (CT) images for visual interpretation. Correlations between D-PET imaging parameters and clinical parameters, i.e. tumor size, grade and clinical status, were calculated with a significance level of 0.05. The temporal uptake pattern of (18)FDG in the tumor varied considerably from patient to patient. SUVE peak was higher than SUVL peak for four patients. The images of the rate constants showed a systematic pattern, often with elevated intensity in the tumors compared to surrounding tissue. Significant correlations were found between SUVE/L and some of the rate parameters. Dynamic (18)FDG-PET may provide additional valuable information on soft tissue sarcomas not obtainable from conventional (18)FDG-PET. The prognostic role of dynamic imaging should be investigated.

Dual-time-point 18F-FDG PET imaging for diagnosis of disease type and disease activity in patients with idiopathic interstitial pneumonia

International Nuclear Information System (INIS)

Umeda, Yukihiro; Demura, Yoshiki; Ishizaki, Takeshi; Ameshima, Shingo; Miyamori, Isamu; Saito, Yuji; Tsuchida, Tatsuro; Fujibayashi, Yasuhisa; Okazawa, Hidehiko

2009-01-01

Individual clinical courses of idiopathic interstitial pneumonia (IIP) are variable and difficult to predict because the pathology and disease activity are contingent, and chest computed tomography (CT) provides little information about disease activity. In this study, we applied dual-time-point [ 18 F]-fluoro-2-deoxy-D-glucose ( 18 F-FDG) positron emission tomography (PET), commonly used for diagnosis of malignant tumours, to the differential diagnosis and prediction of disease progression in IIP patients. Fifty patients with IIP, including idiopathic pulmonary fibrosis (IPF, n = 21), non-specific interstitial pneumonia (NSIP, n = 18) and cryptogenic organizing pneumonia (COP, n = 11), underwent 18 F-FDG PET examinations at two time points: scan 1 at 60 min (early imaging) and scan 2 at 180 min (delayed imaging) after 18 F-FDG injection. The standardized uptake values (SUV) at the two points and the retention index (RI-SUV) calculated from them were evaluated and compared with chest CT findings, disease progression and disease types. To evaluate short-term disease progression, all patients were examined by pulmonary function test every 3 months for 1 year after 18 F-FDG PET scanning. The early SUV for COP (2.47 ± 0.74) was significantly higher than that for IPF (0.99 ± 0.29, p = 0.0002) or NSIP (1.22 ± 0.44, p= 0.0025). When an early SUV cut-off value of 1.5 and greater was used to distinguish COP from IPF and NSIP, the sensitivity, specificity and accuracy were 90.9, 94.3 and 93.5%, respectively. The RI-SUV for IPF and NSIP lesions was significantly greater in patients with deteriorated pulmonary function after 1 year of follow-up (progressive group, 13.0 ± 8.9%) than in cases without deterioration during the 1-year observation period (stable group, -16.8 ± 5.9%, p 18 F-FDG PET are useful parameters for the differential diagnosis and prediction of disease progression in patients with IIP. (orig.)

A click chemistry approach to glycomimetics: Michael addition of 2,3,4,6-tetra-O-acetyl-1-thio-beta-D-glucopyranose to 4-deoxy-1,2-O-isopropylidene-L-glycero-pent-4-enopyranos-3-ulose--a convenient route to novel 4-deoxy-(1-->5)-5-C-thiodisaccharides.

Science.gov (United States)

Witczak, Zbigniew J; Lorchak, David; Nguyen, Nguyen

2007-09-03

The base catalyzed conjugate Michael addition of the 1-thiosugar, 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranose, 1, to a new highly reactive enone 4-deoxy-1,2-O-isopropylidene-L-glycero-pent-4-enopyranos-3-ulose, 2, proceeds steroselectively with formation of adduct 3 in 94% yield. Convenient stereoselective reduction of the C-3 keto function of 3 with L-Selectride followed by in situ acetylation produces thiodisaccharide 4 in good 82% yield. Cleavage of the 1,2-O-isopropylidene protecting group with p-toluenesulfonic acid in methanol, followed by de-O-acetylation, produced an inseparable anomeric mixture of methyl 4-deoxy-5-C-(beta-D-glucopyranosyl)-thio-alpha/beta-L-ribo-pyranoside 5 in 72% overall yield. This approach constitutes a new general two-step click chemistry route to the previously unknown class of 4-deoxy-(1-->5)-5-C-thiodisaccharides as stable and biologically important glycomimetics.

Brain glucose metabolism in diffuse large B-cell lymphoma patients as assessed with FDG-PET: impact on outcome and chemotherapy effects.

Science.gov (United States)

Adams, Hugo Ja; de Klerk, John Mh; Fijnheer, Rob; Heggelman, Ben Gf; Dubois, Stefan V; Nievelstein, Rutger Aj; Kwee, Thomas C

2016-06-01

There is a lack of data on the effect of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy on brain glucose metabolism of diffuse large B-cell lymphoma (DLBCL) patients, as measured by 18F-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Moreover, the prognostic value of brain glucose metabolism measurements is currently unknown. To investigate the use of FDG-PET for measurement of brain glucose metabolism in R-CHOP-treated DLBCL patients, and to assess its prognostic value. This retrospective study included DLBCL patients who underwent FDG-PET including the brain. FDG-PET metabolic volume products (MVPs) of the entire brain, cerebral cortex, basal ganglia, and cerebellum were measured, before and after R-CHOP therapy. Whole-body total lesion glycolysis (TLG) was also measured. Thirty-eight patients were included, of whom 18 had an appropriate end-of-treatment FDG-PET scan. There were no significant differences (P > 0.199) between pre- and post-treatment brain glucose metabolism metrics. Low basal ganglia MVP was associated with a significantly worse progression-free survival (PFS) and overall survival (OS) (P = 0.020 and P = 0.032), and low cerebellar MVP was associated with a significantly worse OS (P = 0.034). There were non-significant very weak correlations between pretreatment brain glucose metabolism metrics and TLG. In the multivariate Cox regression, only the National Comprehensive Cancer Network International Prognostic Index (NCCN-IPI) remained an independent predictor of PFS (hazard ratio 3.787, P = 0.007) and OS (hazard ratio 2.903, P = 0.0345). Brain glucose metabolism was not affected by R-CHOP therapy. Low pretreatment brain glucose metabolism was associated with a worse outcome, but did not surpass the predictive value of the NCCN-IPI. © The Foundation Acta Radiologica 2015.

Comparison among conventional and advanced MRI, 18F-FDG PET/CT, phenotype and genotype in glioblastoma.

Science.gov (United States)

Valentini, Maria Consuelo; Mellai, Marta; Annovazzi, Laura; Melcarne, Antonio; Denysenko, Tetyana; Cassoni, Paola; Casalone, Cristina; Maurella, Cristiana; Grifoni, Silvia; Fania, Piercarlo; Cistaro, Angelina; Schiffer, Davide

2017-10-31

Glioblastoma (GB) is a highly heterogeneous tumor. In order to identify in vivo the most malignant tumor areas, the extent of tumor infiltration and the sites giving origin to GB stem cells (GSCs), we combined positron emission tomography/computed tomography (PET/CT) and conventional and advanced magnetic resonance imaging (MRI) with histology, immunohistochemistry and molecular genetics. Prior to dura opening and tumor resection, forty-eight biopsy specimens [23 of contrast-enhancing (CE) and 25 of non-contrast enhancing (NE) regions] from 12 GB patients were obtained by a frameless image-guided stereotactic biopsy technique. The highest values of 2-[18F]-fluoro-2-deoxy-D-glucose maximum standardized uptake value ( 18 F-FDG SUV max ), relative cerebral blood volume (rCBV), Choline/Creatine (Cho/Cr), Choline/N-acetylaspartate (Cho/NAA) and Lipids/Lactate (LL) ratio have been observed in the CE region. They corresponded to the most malignant tumor phenotype, to the greatest molecular spectrum and stem cell potential. On the contrary, apparent diffusion coefficient (ADC) and fractional anisotropy (FA) in the CE region were very variable. 18 F-FDG SUV max , Cho/Cr and Cho/NAA ratio resulted the most suitable parameters to detect tumor infiltration. In edematous areas, reactive astrocytes and microglia/macrophages were influencing variables. Combined MRI and 18 F-FDG PET/CT allowed to recognize the specific biological significance of the different identified areas of GB.

Pharmacokinetic and toxicological evaluation of multi-functional thiol-6-fluoro-6-deoxy-d-glucose gold nanoparticles in vivo

Science.gov (United States)

Roa, Wilson; Xiong, Yeping; Chen, Jie; Yang, Xiaoyan; Song, Kun; Yang, Xiaohong; Kong, Beihua; Wilson, John; Xing, James Z.

2012-09-01

We synthesized a novel, multi-functional, radiosensitizing agent by covalently linking 6-fluoro-6-deoxy-d-glucose (6-FDG) to gold nanoparticles (6-FDG-GNPs) via a thiol functional group. We then assessed the bio-distribution and pharmacokinetic properties of 6-FDG-GNPs in vivo using a murine model. At 2 h, following intravenous injection of 6-FDG-GNPs into the murine model, approximately 30% of the 6-FDG-GNPs were distributed to three major organs: the liver, the spleen and the kidney. PEGylation of the 6-FDG-GNPs was found to significantly improve the bio-distribution of 6-FDG-GNPs by avoiding unintentional uptake into these organs, while simultaneously doubling the cellular uptake of GNPs in implanted breast MCF-7 adenocarcinoma. When combined with radiation, PEG-6-FDG-GNPs were found to increase the apoptosis of the MCF-7 breast adenocarinoma cells by radiation both in vitro and in vivo. Pharmacokinetic data indicate that GNPs reach their maximal concentrations at a time window of two to four hours post-injection, during which optimal radiation efficiency can be achieved. PEG-6-FDG-GNPs are thus novel nanoparticles that preferentially accumulate in targeted cancer cells where they act as potent radiosensitizing agents. Future research will aim to substitute the 18F atom into the 6-FDG molecule so that the PEG-6-FDG-GNPs can also function as radiotracers for use in positron emission tomography scanning to aid cancer diagnosis and image guided radiation therapy planning.

Schooling mediates brain reserve in Alzheimer's disease: findings of fluoro-deoxy-glucose-positron emission tomography.

Science.gov (United States)

Perneczky, R; Drzezga, A; Diehl-Schmid, J; Schmid, G; Wohlschläger, A; Kars, S; Grimmer, T; Wagenpfeil, S; Monsch, A; Kurz, A

2006-09-01

Functional imaging studies report that higher education is associated with more severe pathology in patients with Alzheimer's disease, controlling for disease severity. Therefore, schooling seems to provide brain reserve against neurodegeneration. To provide further evidence for brain reserve in a large sample, using a sensitive technique for the indirect assessment of brain abnormality (18F-fluoro-deoxy-glucose-positron emission tomography (FDG-PET)), a comprehensive measure of global cognitive impairment to control for disease severity (total score of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Battery) and an approach unbiased by predefined regions of interest for the statistical analysis (statistical parametric mapping (SPM)). 93 patients with mild Alzheimer's disease and 16 healthy controls underwent 18F-FDG-PET imaging of the brain. A linear regression analysis with education as independent and glucose utilisation as dependent variables, adjusted for global cognitive status and demographic variables, was conducted in SPM2. The regression analysis showed a marked inverse association between years of schooling and glucose metabolism in the posterior temporo-occipital association cortex and the precuneus in the left hemisphere. In line with previous reports, the findings suggest that education is associated with brain reserve and that people with higher education can cope with brain damage for a longer time.

Effects of acupuncture at HT7 on glucose metabolism in a rat model of Alzheimer's disease: an 18F-FDG-PET study

OpenAIRE

Lai, Xinsheng; Ren, Jie; Lu, Yangjia; Cui, Shaoyang; Chen, Junqi; Huang, Yong; Tang, Chunzhi; Shan, Baoci; Nie, Bingbing

2015-01-01

Objective To explore the effects of acupuncture at HT7 on different cerebral regions in a rat model of Alzheimer's disease (AD) with the application of 18F-2-fluoro-deoxy-D-glucose positron emission tomography (FDG-PET). Methods Sixty Wistar rats were included after undergoing a Y-maze electric sensitivity test. Ten rats were used as a healthy control group. The remaining 50 rats were injected stereotaxically with ibotenic acid into the right nucleus basalis magnocellularis and injected intra...

Imaging of primary central nervous system lymphoma

Energy Technology Data Exchange (ETDEWEB)

Tang, Y.Z., E-mail: yenzhitang@doctors.net.uk [Royal Free Hospital, London (United Kingdom); Booth, T.C.; Bhogal, P.; Malhotra, A.; Wilhelm, T. [Royal Free Hospital, London (United Kingdom)

2011-08-15

Primary central nervous system lymphoma (PCNSL) comprises 5% of all primary brain tumours. PCNSL demonstrates a variety of well-documented imaging findings, which can vary depending on immune status and histological type. Imaging features of PCNSL may overlap with other tumours and infection making definitive diagnosis challenging. In addition, several rare variants of PCNSL have been described, each with their own imaging characteristics. Advanced imaging techniques including 2-[{sup 18}F]-fluoro-2-deoxy-D-glucose ({sup 18}FDG) and {sup 11}C positron-emission tomography (PET), {sup 201}Tl single-photon emission computed tomography (SPECT), {sup 1}H-magnetic resonance spectroscopy (MRS), and MR perfusion, have been used to aid differentiation of PCNSL from other tumours. Ultimately, no imaging method can definitively diagnose PCNSL, and histology is required.

Radiosynthesis and biological evaluation of N-(2-[18F]fluoropropionyl)-3,4-dihydroxy-l-phenylalanine as a PET tracer for oncologic imaging.

Science.gov (United States)

Tang, Caihua; Nie, Dahong; Tang, Ganghua; Gao, Siyuan; Liu, Shaoyu; Wen, Fuhua; Tang, Xiaolan

2017-07-01

Several 11 C and 18 F labeled 3,4-dihydroxy-l-phenylalanine (l-DOPA) analogues have been used for neurologic and oncologic diseases, especially for brain tumors and neuroendocrine tumors PET imaging. However, 18 F-labeled N-substituted l-DOPA analogues have not been reported so far. In the current study, radiosynthesis and biological evaluation of a new 18 F-labeled l-DOPA analogue, N-(2-[ 18 F]fluoropropionyl)-3,4-dihydroxy-l-phenylalanine ([ 18 F]FPDOPA) for tumor PET imaging are performed. The synthesis of [ 18 F]FPDOPA was via a two-step reaction sequence from 4-nitrophenyl-2-[ 18 F]fluoropropionate ([ 18 F]NFP). The biodistribution of [ 18 F]FPDOPA was determined in normal Kunming mice. In vitro competitive inhibition and protein incorporation experiments were performed with SPC-A-1 lung adenocarcinoma cell lines. PET/CT studies of [ 18 F]FPDOPA were conducted in C6 rat glioma and SPC-A-1 human lung adenocarcinoma and H460 human large cell lung cancer-bearing nude mice. [ 18 F]FPDOPA was prepared with a decay-corrected radiochemical yield of 28±5% and a specific activity of 50±15GBq/μmol (n=10) within 125min. In vitro cell experiments showed that [ 18 F]FPDOPA uptake in SPC-A-1 cells was primarily transported through Na + -independent system L, with Na + -dependent system B 0,+ and system ASC partly involved in it. Biodistribution data in mice showed that renal-bladder route was the main excretory system of [ 18 F]FPDOPA. PET imaging demonstrated intense accumulation of [ 18 F]FPDOPA in several tumor xenografts, with (8.50±0.40)%ID/g in C6 glioma, (6.30±0.12)%ID/g in SPC-A-1 lung adenocarcinoma, and (6.50±0.10)%ID/g in H460 large cell lung cancer, respectively. A novel N-substituted 18 F-labeled L-DOPA analogue [ 18 F]FPDOPA is synthesized and evaluated in vitro and in vivo. The results support that [ 18 F]FPDOPA seems to be a potential PET tracer for tumor imaging, especially be a better potential PET tracer than [ 18 F]fluoro-2-deoxy-d-glucose ([ 18 F

{sup 18}F-FDG uptake on PET in primary mediastinal non-thymic neoplasm: A clinicopathological study

Energy Technology Data Exchange (ETDEWEB)

Kaira, Kyoichi, E-mail: kkaira1970@yahoo.co.jp [Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Abe, Masato [Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Nakagawa, Kazuo; Ohde, Yasuhisa; Okumura, Takehiro [Division of Thoracic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Takahashi, Toshiaki; Murakami, Haruyasu; Shukuya, Takehito; Kenmotsu, Hirotsugu; Naito, Tateaki [Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Hayashi, Isamu [Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Oriuchi, Noboru [Department of Diagnostic Radiology and Nuclear medicine, Gunma University Graduate School of Medicine, Showa-machi, Maebashi 371-8511, Gunma (Japan); Endo, Masahiro [Division of Diagnostic Radiology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Kondo, Haruhiko [Division of Thoracic Surgery, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Nakajima, Takashi [Division of Pathology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan); Yamamoto, Nobuyuki [Division of Thoracic Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi-cho, Sunto-gun, Shizuoka 411-8777 (Japan)

2012-09-15

Background: The usefulness of 2-[{sup 18}F]-fluoro-2-deoxy-D-glucose ({sup 18}F-FDG) positron emission tomography (PET) has been investigated in thymic epithelial tumors. However, little is known about PET imaging of {sup 18}F-FDG in primary non-thymic mediastinal neoplasms. The aim of this study is to explore the clinicopathological significance of {sup 18}F-FDG PET in primary mediastinal (non-thymic) neoplasms. Methods: Twenty-one patients with mediastinal neoplasms who underwent {sup 18}F-FDG PET before treatment were included in this study. Tumor sections were stained by immunohistochemistry for glucose transporter 1 (Glut1); glucose transporter 3 (Glut3); hypoxia-inducible factor-1 alpha (HIF-1α); hexokinase I; vascular endothelial growth factor (VEGF); microvessels (CD34); epidermal growth factor receptor (EGFR); Akt/mTOR signaling pathway (p-Akt and p-mTOR); cell cycle control (p53). Results: Seventeen of 21 patients were imaged on PET system using {sup 18}F-FDG, but 4 patients with a histology of cyst showed nothing abnormal in PET scans. The histology of the resected tumors was as follows: 6 schwannoma, 3 teratoma, 4 cyst, 3 sarcoma, 1 undifferentiated carcinoma, 1 seminoma, 1 mediastinal goiter, 1 ganglioneuroma, and 1 Hodgkin lymphoma. {sup 18}F-FDG uptake was significantly correlated with Glut1, HIF-1α, EGFR, p-Akt and p-S6K. These biomarkers were highly expressed in schwannoma, teratoma and high grade malignancies, whereas all patients with cyst and ganglioneuroma had no positive expression of these biomarkers. High uptake of {sup 18}F-FDG was significant associated with Glut1, VEGF, EGFR, p-Akt, p-S6K and tumor maximal size. Conclusion: The amount of {sup 18}F-FDG uptake in primary mediastinal non-thymic neoplasms is determined by the presence of glucose metabolism (Glut1), hypoxia (HIF-1α) and upstream components of HIF-1α (EGFR, p-Akt and p-S6K)

In Vivo 6-([18F]Fluoroacetamido-1-hexanoicanilide PET Imaging of Altered Histone Deacetylase Activity in Chemotherapy-Induced Neurotoxicity

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Nobuyoshi Fukumitsu

2018-01-01

Full Text Available Background. Histone deacetylases (HDACs regulate gene expression by changing histone deacetylation status. Neurotoxicity is one of the major side effects of cisplatin, which reacts with deoxyribonucleic acid (DNA and has excellent antitumor effects. Suberoylanilide hydroxamic acid (SAHA is an HDAC inhibitor with neuroprotective effects against cisplatin-induced neurotoxicity. Purpose. We investigated how cisplatin with and without SAHA pretreatment affects HDAC expression/activity in the brain by using 6-([18F]fluoroacetamido-1-hexanoicanilide ([18F]FAHA as a positron emission tomography (PET imaging agent for HDAC IIa. Materials and Methods. [18F]FAHA and [18F]fluoro-2-deoxy-2-D-glucose ([18F]FDG PET studies were done in 24 mice on 2 consecutive days and again 1 week later. The mice were divided into three groups according to drug administration between the first and second imaging sessions (Group A: cisplatin 2 mg/kg, twice; Group B: cisplatin 4 mg/kg, twice; Group C: cisplatin 4 mg/kg, twice, and SAHA 300 mg/kg pretreatment, 4 times. Results. The Ki value of [18F]FAHA was increased and the percentage of injected dose/tissue g (% ID/g of [18F]FDG was decreased in the brains of animals in Groups A and B. The Ki value of [18F]FAHA and % ID/g of [18F]FDG were not significantly different in Group C. Conclusions. [18F]FAHA PET clearly showed increased HDAC activity suggestive of cisplatin neurotoxicity in vivo, which was blocked by SAHA pretreatment.

Early interim 18F-FDG PET in Hodgkin's lymphoma: evaluation on 304 patients

International Nuclear Information System (INIS)

Zinzani, Pier Luigi; Stefoni, Vittorio; Broccoli, Alessandro; Argnani, Lisa; Baccarani, Michele; Rigacci, Luigi; Puccini, Benedetta; Castagnoli, Antonio; Vaggelli, Luca; Zanoni, Lucia; Fanti, Stefano

2012-01-01

The use of early (interim) PET restaging during first-line therapy of Hodgkin's lymphoma (HL) in clinical practice has considerably increased because of its ability to provide early recognition of treatment failure allowing patients to be transferred to more intensive treatment regimens. Between June 1997 and June 2009, 304 patients with newly diagnosed HL (147 early stage and 157 advanced stage) were treated with the ABVD regimen at two Italian institutions. Patients underwent PET staging and restaging at baseline, after two cycles of therapy and at the end of the treatment. Of the 304 patients, 53 showed a positive interim PET scan and of these only 13 (24.5%) achieved continuous complete remission (CCR), whereas 251 patients showed a negative PET scan and of these 231 (92%) achieved CCR. Comparison between interim PET-positive and interim PET-negative patients indicated a significant association between PET findings and 9-year progression-free survival and 9-year overall survival, with a median follow-up of 31 months. Among the early-stage patients, 19 had a positive interim PET scan and only 4 (21%) achieved CCR; among the 128 patients with a negative interim PET scan, 122 (97.6%) achieved CCR. Among the advanced-stage patients, 34 showed a persistently positive PET scan with only 9 (26.4%) achieving CCR, whereas 123 showed a negative interim PET scan with 109 (88.6%) achieving CCR. Our results demonstrate the role of an early PET scan as a significant step forward in the management of patients with early-stage or advanced-stage HL. (orig.)

Effects of 2-Deoxy-D-Glucose on Metabolic Status, Proliferative Capacity and Growth Rate of FSall Tumor: Observations made by In Vivo 31P-Nuclear Magnetic Resonance Spectroscopy and Flow Cytometry

International Nuclear Information System (INIS)

Chang, Hye Sook; Choi, Eun Kyung; Cho, Jeong Gill; Lim, Tae Hwan; Lee, Tae Keun; Yi, Yun; Cho, Young Joo; Kim, Gon Sup

1991-01-01

The effect of 2-deoxy-d-glucose (2-DDG) on C 3 H mouse fibrosarcoma (FSall) was studied. Metabolic status, especially for energy metabolism, was studied using in vivo 31 P-MRS, proliferative capacity was observed on flow cytometry (FC) and growth rate was measured after transplantation of 106 viable tumor cells in the dorsum of foot of C 3 Hf/Sed mice. One gram of 2-DDG per kg of body weight was injected intraperitoneally on 12th day of implantation. Average tumor size on 12th day of implantation was 250mm 3 . Growth rate of FSall tumor was measured by tumor doubling time between tumor age 5-12 days was 0.84 days with slope 0.828 and tumor doubling time between tumor age 13-28 days was 3.2 days with slope 0.218 in control group. After 2-DDG injection, tumor doubling time was elongated to 5.1 days with slope 0.136. The effect of 2-DDG studied in vivo 31 P-MRS suggested that the increase of phosphomonoester (PME) and inorganic phosphate (Pi) by increasing size of tumor, slowed down after 2-DDG injection. Flow cytometry showed significantly increased S-phase and G 2 +M phase fraction suggesting increased proliferative capacity of tumor cells in the presence of 2-DDG. Authors observed an interesting effect 2-DDG on FSall tumor and attempt to utilize as an adjunct for radiotherapy

Comparison of pharmacokinetic MRI and [18F] fluorodeoxyglucose PET in the diagnosis of breast cancer: initial experience

International Nuclear Information System (INIS)

Brix, G.; Henze, M.; Knopp, M.V.; Doll, J.; Hawighorst, H.; Lucht, R.; Junkermann, H.; Haberkorn, U.

2001-01-01

It was the aim of this methodology-oriented clinical pilot study to compare the potential of dynamic MRI and 2-[ 18 F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) for the detection and characterization of breast cancer. Fourteen women with suspicious breast lesions were examined. The MRI data were acquired with a turbo fast low-angle shot sequence and analyzed using a pharmacokinetic model. Emission data were detected in the sensitive 3D modus, iteratively reconstructed, and superimposed onto corresponding transmission images. In the 14 patients, 13 breast masses with a suspicious contrast enhancement and FDG uptake were detected. For these lesions, no statistically significant correlation between evaluated MR and PET parameters was found. Of the 9 histologically confirmed carcinomas, 8 were correctly characterized with MRI and PET. Two inflammatory lesions were concordantly classified as cancer. Moreover, dynamic MRI yielded another false-positive finding. In 6 patients, PET detected occult lymph node and/or distant metastases. Although both functional imaging techniques provide independent tissue information, the results concerning the diagnosis of primary breast lesions were almost identical. An advantage of PET, however, is its ability to localize lymph node involvement and distant metastases as an integral part of the examination. (orig.)

2´-deoxy-5,6-dihydro-5-azacytidine - a less toxic alternative of 2´-deoxy-5-azacytidine: a comparative study of hypomethylating potential.

Science.gov (United States)

Matoušová, Marika; Votruba, Ivan; Otmar, Miroslav; Tloušťová, Eva; Günterová, Jana; Mertlíková-Kaiserová, Helena

2011-06-01

Restoration of transcriptionally silenced genes by means of methyltransferases inhibitors plays a crucial role in the current therapy of myelodysplastic syndromes and certain types of leukemias. A comparative study of hypomethylating activities of a series of 5-azacytidine nucleosides: 5-azacytidine (AC), 2'-deoxy-5-azacytidine (DAC) and its α-anomer (α-DAC), 5,6-dihydro-5-azacytidine (DHAC), 2'-deoxy-5,6-dihydro-5-azacytidine (DHDAC, KP-1212) and its α-anomer (α-DHDAC), and of a 2-pyrimidone ribonucleoside (zebularine) was conducted. Methylation-specific PCR was employed to detect the efficiency of individual agents on cyclin-dependent kinase inhibitor 2B and thrombospondin-1 hypermethylated gene loci. Overall changes in DNA methylation level were quantified by direct estimation of 5-methyl-2'-deoxycytidine-5'-monophosphate by HPLC using digested genomic DNA. Flow cytometric analysis of cell cycle progression and apoptotic markers was used to determine cytotoxicity of the compounds. mRNA expression was measured using qRT-PCR. 2'-deoxy-5,6-dihydro-5-azacytidine was found to be less cytotoxic and more stable than 2'-deoxy-5-azacytidine at the doses that induce comparable DNA hypomethylation and gene reactivation. This makes it a valuable tool for epigenetic research and worth further investigations to elucidate its possible therapeutic potential.

Effects of 2-deoxy-D-glucose and quercetin on the expression of osteonectin and osteopontin during the differentiation of irradiated MC3T3-E1 osteoblastic cells

International Nuclear Information System (INIS)

Yu, Su Kyung; Koh, Kwang Joon; Kim, Kyoung A

2008-01-01

To characterize the effects of 2-deoxy-D-glucose (2-DG) and quercetin (QCT) on gene expression of osteonectin (ON) and osteopontin (OP) in irradiated MC3T3-E1 cells. When MC3T3-E1 osteoblastic cells had reached 70-80% confluence, cultures were transferred to a differentiating medium supplemented with 5 mM 2-DG or 10 μM QCT and then irradiated with 2, 4, 6, and 8 Gy. At various times after irradiation, the cells were analyzed for the expression of bone mineralization genes such as ON and OP. The mRNA expression of both ON and OP was increased according to the culture time in the differentiation medium, and the increase of the genes peaked at 14 days after the differentiation induction. In the case of OP, the increase of mRNA expression was maintained to 28 days after the differentiation, while the mRNA level of ON was reduced to the basal level at the same time. Irradiation adding 2-DG showed a significant peak value in the expression pattern of ON at 4 Gy 7 days after irradiation. Irradiation adding QCT increased the mRNA expression of ON and OP in a dose-dependant manner, but irradiation adding 2-DG did not show any differences between the control and experiments 14 days after irradiation. Irradiation adding QCT increased significantly the expression patterns of ON 21 days after irradiation. The results showed that QCT acted as a radiosensitizer in the gene expression of ON and OP during differentiation of the late stage of irradiated MC3T3-E1 osteoblastic cells in vitro.

Comparison of pharmacokinetic MRI and [{sup 18}F] fluorodeoxyglucose PET in the diagnosis of breast cancer: initial experience

Energy Technology Data Exchange (ETDEWEB)

Brix, G. [Research Program ' ' Radiological Diagnostics and Therapy' ' , German Cancer Research Center (DKFZ), Heidelberg (Germany); Dept. of Medical Radiation Hygiene, Federal Office for Radiation Protection, Oberschleissheim (Germany); Henze, M. [Dept. of Nuclear Medicine, Univ. of Heidelberg, Heidelberg (Germany); Knopp, M.V.; Doll, J.; Hawighorst, H. [Research Program ' ' Radiological Diagnostics and Therapy' ' , German Cancer Research Center (DKFZ), Heidelberg (Germany); Lucht, R. [Dept. of Medical Radiation Hygiene, Federal Office for Radiation Protection, Oberschleissheim (Germany); Junkermann, H. [Dept. of Gynaecological Radiology, Univ. of Heidelberg (Germany); Haberkorn, U. [Research Program ' ' Radiological Diagnostics and Therapy' ' , German Cancer Research Center (DKFZ), Heidelberg (Germany); Dept. of Nuclear Medicine, Univ. of Heidelberg, Heidelberg (Germany)

2001-10-01

It was the aim of this methodology-oriented clinical pilot study to compare the potential of dynamic MRI and 2-[{sup 18}F]fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) for the detection and characterization of breast cancer. Fourteen women with suspicious breast lesions were examined. The MRI data were acquired with a turbo fast low-angle shot sequence and analyzed using a pharmacokinetic model. Emission data were detected in the sensitive 3D modus, iteratively reconstructed, and superimposed onto corresponding transmission images. In the 14 patients, 13 breast masses with a suspicious contrast enhancement and FDG uptake were detected. For these lesions, no statistically significant correlation between evaluated MR and PET parameters was found. Of the 9 histologically confirmed carcinomas, 8 were correctly characterized with MRI and PET. Two inflammatory lesions were concordantly classified as cancer. Moreover, dynamic MRI yielded another false-positive finding. In 6 patients, PET detected occult lymph node and/or distant metastases. Although both functional imaging techniques provide independent tissue information, the results concerning the diagnosis of primary breast lesions were almost identical. An advantage of PET, however, is its ability to localize lymph node involvement and distant metastases as an integral part of the examination. (orig.)

Detection of N-(1-deoxy-D-fructos-1-yl) Fumonisins B₂ and B₃ in Corn by High-Resolution LC-Orbitrap MS.

Science.gov (United States)

Matsuo, Yosuke; Takahara, Kentaro; Sago, Yuki; Kushiro, Masayo; Nagashima, Hitoshi; Nakagawa, Hiroyuki

2015-09-16

The existence of glucose conjugates of fumonisin B₂ (FB₂) and fumonisin B₃ (FB₃) in corn powder was confirmed for the first time. These "bound-fumonisins" (FB₂ and FB₃ bound to glucose) were identified as N-(1-deoxy-D-fructos-1-yl) fumonisin B₂ (NDfrc-FB₂) and N-(1-deoxy-D-fructos-1-yl) fumonisin B₃ (NDfrc-FB₃) respectively, based on the accurate mass measurements of characteristic ions and fragmentation patterns using high-resolution liquid chromatography-Orbitrap mass spectrometry (LC-Orbitrap MS) analysis. Treatment on NDfrc-FB₂ and NDfrc-FB₃ with the o-phthalaldehyde (OPA) reagent also supported that D-glucose binding to FB₂ and FB₃ molecules occurred to their primary amine residues.

Synthesis and evaluation of 68Ga-labeled DOTA-2-deoxy-D-glucosamine as a potential radiotracer in μPET imaging

Science.gov (United States)

Yang, Zhi; Xiong, Chiyi; Zhang, Rui; Zhu, Hua; Li, Chun

2012-01-01

The purposes of this study were to develop an efficient method of labeling D-glucosamine hydrochloride with gallium 68 (68Ga) and investigate the imaging properties of the resulting radiotracer in a human tumor xenograft model using micro-positron emission tomography (μPET). The precursor compound 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-2-deoxy-D-glucosamine (DOTA-DG) was synthesized from D-glucosamine hydrochloride and 2-(4-isothiocyanatobenzyl)-DOTA. Radiolabeling of DOTA-DG with 68Ga was achieved in 10 minutes using microwave heating. The labeling efficiency a nd radiochemical purity after purification of 68Ga-DOTA-DG were ~85% and greater than 98%, respectively. In A431 cells, the percentages of 68Ga-DOTA-DG and 18F-FDG uptakes after 60 min incubation were 15.7% and 16.2%, respectively. In vivo, the mean ± standard deviation of 68Ga-DOTADG uptake values in A431 tumors were 2.38±0.30, 0.75±0.13, and 0.39±0.04 percent of the injected dose per gram of tissue at 10, 30, and 60 minutes after intravenous injection, respectively. μPET imaging of A431-bearing mice clearly delineated tumors at 60 minutes after injection of 68Ga-DOTA-DG at a dose of 3.7 MBq. 68Ga-DOTA-DG displayed significantly higher tumor-to-heart, tumor-to-brain, and tumor-to-muscle ratios than 18F-FDG did. Further studies are needed to identify the mechanism of tumor uptake of this new glucosamine-based PET imaging tracer. PMID:23145365

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

PEComa of the lung

Directory of Open Access Journals (Sweden)

Vijayabhaskar R

2010-01-01

Full Text Available Perivascular epithelioid cell tumor (PEComa, also called clear cell ′′sugar′′ tumor of the lung, is a rare benign tumor arising from perivascular epithelioid cells (PECs. We report a case of a 15-year-old boy who presented with right lower lobe lesion which turned out to be a clear cell tumor of the lung. An [18F]-fluoro-2-deoxy-D-glucose (FDG - positron emission tomography (PET scan revealed mild FDG uptake in the lung lesion (SUV< 1 with no active uptake elsewhere in the body. We discuss the clinical, radiologic and immunohistochemical features of clear cell ′′sugar′′ tumor of lung and compare them with published literature.

The value of dual time point 18F-FDG PET imaging for the differentiation between malignant and benign lesions

International Nuclear Information System (INIS)

Lan, X.-L.; Zhang, Y.-X.; Wu, Z.-J.; Jia, Q.; Wei, H.; Gao, Z.-R.

2008-01-01

Aim: To assess the clinical value of dual time point 2-[ 18 F]-fluoro-2-deoxy-D-glucose positron emission tomography ( 18 F-FDG PET) imaging for the differentiation between malignant and benign lesions. Materials and methods: Ninety-six patients (28 patients with primary lung cancer, 18 patients with digestive system carcinoma, 13 patients with other malignant tumours, and 37 patients with benign lesions) underwent FDG-PET/CT at two time points: examination 1 at 45-55 min and examination 2 at 160 ± 24 (150-180) min after the intravenous injection of 233 ± 52 (185-370) MBq 18 F-FDG. Reconstructed images were evaluated qualitatively and quantitatively. The maximum standardized uptake values (SUVmax) of the lesions were calculated for both time points. An increase was considered to have occurred if the SUVs at examination 2 had increased by >10% as compared with those at the examination 1. Results: The lesions in 24 of 28 (86%) patients with primary lung cancer had an SUVmax ≥2.5 at examination 1. Of these, SUVmax values increased in 23 patients, but had not changed in one patient, at examination 2. The lesions in the other four patients with primary lung tumour had SUVmax values between 1.5 and 2.5 at examination 1, which were considered as suspected positive, increased SUVmax values were observed in three of these patients at examination 2. The malignant lesions in 17 of 18 patients with digestive system carcinoma showed SUVmax values ≥2.5 and only one patient had an SUVmax value 18 F-FDG PET imaging is an important noninvasive method for the differentiation of malignant and nonmalignant lesions

Cerebral metabolism, anatomy, and cognition in monozygotic twins discordant for dementia of the Alzheimer type.

Science.gov (United States)

Luxenberg, J S; May, C; Haxby, J V; Grady, C; Moore, A; Berg, G; White, B J; Robinette, D; Rapoport, S I

1987-03-01

One pair of monozygotic twins discordant for dementia of the Alzheimer type (DAT) was studied using neuropsychological testing, quantitative x-ray computed tomography (QCT) and magnetic resonance imaging (MRI) of the brain. Cerebral glucose metabolism was measured using positron emission tomography (PET) and 2-[18-F]fluoro-2-deoxy-D-glucose (FDG). The affected twin had a seven year history of progressive cognitive impairment and was severely demented. Neuropsychological testing of the affected twin demonstrated marked deficits in all areas of cognitive function. The asymptomatic twin showed some impairment on tests of perceptual organisation and delayed recall. The affected twin had loss of gray matter and ventricular enlargement on QCT and MRI compared with healthy controls (p less than 0.05). He also had frontal and parietal lobe hypometabolism and increased asymmetry of metabolism on PET compared to both his twin and healthy age-matched controls (p less than 0.05). PET, QCT, and MRI distinguished changes in the twin with DAT compared with his brother and healthy controls. Although the subtle neuropsychological abnormalities of the asymptomatic twin may be signs of early DAT, they were not accompanied by any changes in regional cerebral metabolism or brain structure.

Synthesis of 5'-deoxy-5'-[18F]fluoro-adenosine by radiofluorination of 5'-deoxy-5'-haloadenosine derivatives

International Nuclear Information System (INIS)

Lehel, Sz.; Horvath, G.; Boros, I.; Mikecz, P.; Marian, T.; Tron, L.; Hungarian Academy of Science, Budapest

2000-01-01

5'-Deoxy-5'-[ 18 F]fluoro-adenosine was synthesised by nucleophilic radiofluorination reactions of 5'-deoxy-5'-haloadenosines. The homogeneous isotope exchange in 5'-deoxy-5'-fluoro-adenosine was also investigated. The conversion of these reactions ws found to be rather low and depends on the strength of the halogen-carbon bond: 0.248% for chloride-, 0.488% for bromide- and 1.070% for iodide-derivative; there was no reaction observed in the case of fluoro-compound. (author)

2′-deoxy-5,6-dihydro-5-azacytidine—a less toxic alternative of 2′-deoxy-5-azacytidine: A comparative study of hypomethylating potential

OpenAIRE

Matoušová, Marika; Votruba, Ivan; Otmar, Miroslav; Tloušťová, Eva; Günterová, Jana; Mertlíková-Kaiserová, Helena

2011-01-01

Restoration of transcriptionally silenced genes by means of methyltransferases inhibitors plays a crucial role in the current therapy of myelodysplastic syndromes and certain types of leukemias. A comparative study of hypomethylating activities of a series of 5-azacytidine nucleosides: 5-azacytidine (AC), 2′-deoxy-5-azacytidine (DAC) and its α-anomer (α-DAC), 5,6-dihydro-5-azacytidine (DHAC), 2′-deoxy-5,6-dihydro-5-azacytidine (DHDAC, KP-1212) and its α-anomer (α-DHDAC), and of a 2-pyrimidone...

Synthesis of hypoxia imaging agent 1-(5-deoxy-5-fluoro-α-D-arabinofuranosyl)-2-nitroimidazole using microfluidic technology

International Nuclear Information System (INIS)

Bouvet, Vincent R.; Wuest, Melinda; Wiebe, Leonard I.; Wuest, Frank

2011-01-01

Introduction: Microfluidic technology allows fast reactions in a simple experimental setup, while using very low volumes and amounts of starting material. Consequently, microfluidic technology is an ideal tool for radiolabeling reactions involving short-lived positron emitters. Optimization of the complex array of different reaction conditions requires knowledge of the different reaction parameters linked to the microfluidic system as well as their influence on the radiochemical yields. 1-(5-Deoxy-5-fluoro-α-D-arabinofuranosyl)-2-nitroimidazole ([ 18 F]FAZA) is a frequently used radiotracer for PET imaging of tumor hypoxia. The present study describes the radiosynthesis of [ 18 F]FAZA by means of microfluidic technology and subsequent small animal PET imaging in EMT-6 tumor-bearing mice. Methods: Radiosyntheses were performed using the NanoTek Microfluidic Synthesis System (Advion BioSciences, Inc.). Optimal reaction conditions were studied through screening different reaction parameters like temperature, flow rate, residency time, concentration of the labeling precursor (1-(2,3-di-O-acetyl-5-O-tosyl-α-D-arabinofuranosyl)-2-nitroimidazole) and the applied volume ratio between the labeling precursor and [ 18 F]fluoride. Results: Optimized reaction conditions at low radioactivity levels (1 to 50 MBq) afforded 63% (decay-corrected) of HPLC-purified [ 18 F]FAZA within 25 min. Higher radioactivity levels (0.4 to 2.1 GBq) gave HPLC-purified [ 18 F]FAZA in radiochemical yields of 40% (decay-corrected) within 60 min at a specific activity in the range of 70 to 150 GBq/μmol. Small animal PET studies in EMT-6 tumor-bearing mice showed radioactivity accumulation in the tumor (SUV 20min 0.74 ± 0.08) resulting in an increasing tumor-to-muscle ratio over time. Conclusions: Microfluidic technology is an ideal method for the rapid and efficient radiosynthesis of [ 18 F]FAZA for preclinical radiopharmacological studies. Careful analysis of various reaction parameters is an

Investigation of 18F-2-deoxyglucose for the measure of myocardial glucose metabolism

International Nuclear Information System (INIS)

Phelps, M.E.; Hoffman, E.J.; Selin, C.; Huang, S.C.; Robinson, G.; MacDonald, N.; Schelbert, H.R.; Kuhl, D.E.

1977-01-01

18 F labeled 2-deoxyglucose ( 18 FDG) was studied as a glucose analog. Myocardial uptake and retention, blood clearance, species (dog, monkey, man) dependence and effect of diet on uptake were investigated. Normal myocardial uptake of 18 FDG was 3 to 4% in dog and monkey and 1 to 4% of injected dose in man compared to brain uptake of 2% in dog, 5 to 6% in monkey and 4 to 8% in man. The metabolic rate (MR) for glucose in non-fasting (glycolytic state) was 2.8 times greater than in fasting (ketogenic state). Human subjects showed higher myocardial uptake after a normal meal than after meal containing mostly free fatty acids (FFA). Blood clearance was rapid with initial clearance t 1 / 2 of 0.2 to 0.3 min followed by a t 1 / 2 of 8.4 +- 1.2 min in dog and 11.6 +- 1.1 min in man. A small third component had a t 1 / 2 of 59 +- 10 min and 88 +- 4 min in dog and man, respectively. High image contrast ratios between heart and blood (dog 3.5/1; man 14/1), heart and lung (dog 9/1; man 20/1), heart and liver (dog 15/1; man 10/1) were found with the ECAT positron tomograph. 18 FDG was found to be rapidly taken up by the myocardium without any significant tissue clearance over a 4 hour period. 18 FDG is transported, phosphorylated to 18 FDG-6-PO 4 and trapped in myocardial cells in the same manner as has been found for brain and exhibits excellent imaging properties. Determination of glucose and FFA MR in vivo with ECT provides a method for investigation and assessment of changing aerobic and anaerobic metabolic rates in ischemic heart disease in man

Decline in cerebral glucose utilisation and cognitive function with aging in Down's syndrome.

OpenAIRE

Schapiro, M B; Haxby, J V; Grady, C L; Duara, R; Schlageter, N L; White, B; Moore, A; Sundaram, M; Larson, S M; Rapoport, S I

1987-01-01

The cerebral metabolic rate for glucose (CMRglc) was measured with positron emission tomography and [18F]2-fluoro-2-deoxy-D-glucose in 14 healthy subjects with Down's syndrome, 19 to 33 years old, and in six healthy Down's syndrome subjects over 35 years, two of whom were demented. Dementia was diagnosed from a history of mental deterioration, disorientation and hallucinations. All Down's syndrome subjects were trisomy 21 karyotype. CMRglc also was examined in 15 healthy men aged 20-35 years ...

NIH Conference. Brain imaging: aging and dementia

International Nuclear Information System (INIS)

Cutler, N.R.; Duara, R.; Creasey, H.; Grady, C.L.; Haxby, J.V.; Schapiro, M.B.; Rapoport, S.I.

1984-01-01

The brain imaging techniques of positron emission tomography using [18F]-fluoro-2-deoxy-D-glucose, and computed tomography, together with neuropsychological tests, were used to examine overall brain function and anatomy in three study populations: healthy men at different ages, patients with presumptive Alzheimer's disease, and adults with Down's syndrome. Brain glucose use did not differ with age, whereas an age-related decrement in gray matter volume was found on computed tomographic assessment in healthy subjects. Memory deficits were found to precede significant reductions in brain glucose utilization in mild to moderate Alzheimer's dementia. Furthermore, differences between language and visuoconstructive impairments in patients with mild to moderate Alzheimer's disease were related to hemispheric asymmetry of brain metabolism. Brain glucose utilization was found to be significantly elevated in young adults with Down's syndrome, compared with controls. The importance of establishing strict criteria for selecting control subjects and patients is explained in relation to the findings

F-19 MR imaging of glucose metabolism in the rat and rabbit

International Nuclear Information System (INIS)

Nakada, T.; Kwee, I.L.; Card, P.J.; Matwiyoff, N.A.; Griffey, B.V.; Griffey, R.H.

1987-01-01

MR imaging reflecting regional pathway specific glucose metabolism was performed utilizing F-19 as the MR signal probe and two fluorinated glucose analogues, 2-fluoro-2-deoxy-D-glucose (2-FDG) and 3-fluoro-3-deoxy-D-glucose (3-FDG) as the metabolic probe. 2-FDG-6-phosphate images provides regional quantitative information regarding glycolytic activities, while 2-FDG-6-phosphoglyconate images provide information on the pentose monophosphate shunt activities. 3-FDG-sorbitol and 3-FDG-fructose indicate regional aldose reductase and sorbitol dehydrogenase activities of the aldose reductase sorbitol pathway, respectively. The potential toxicity of 2-FDG in high doses precludes the immediate application of the 2-FDG MR imaging method to humans. The extremely low toxicity of 3-FDG, however, indicates promise for clinical application of 3-FDG MR imaging

Carbon-free production of 2-deoxy-scyllo-inosose (DOI) in cyanobacterium Synechococcus elongatus PCC 7942.

Science.gov (United States)

Watanabe, Satoru; Ozawa, Hiroaki; Kato, Hiroaki; Nimura-Matsune, Kaori; Hirayama, Toshifumi; Kudo, Fumitaka; Eguchi, Tadashi; Kakinuma, Katsumi; Yoshikawa, Hirofumi

2018-01-01

Owing to their photosynthetic capabilities, there is increasing interest in utilizing cyanobacteria to convert solar energy into biomass. 2-Deoxy-scyllo-inosose (DOI) is a valuable starting material for the benzene-free synthesis of catechol and other benzenoids. DOI synthase (DOIS) is responsible for the formation of DOI from d-glucose-6-phosphate (G6P) in the biosynthesis of 2-deoxystreptamine-containing aminoglycoside antibiotics such as neomycin and butirosin. DOI fermentation using a recombinant Escherichia coli strain has been reported, although a carbon source is necessary for high-yield DOI production. We constructed DOI-producing cyanobacteria toward carbon-free and sustainable DOI production. A DOIS gene derived from the butirosin producer strain Bacillus circulans (btrC) was introduced and expressed in the cyanobacterium Synechococcus elongatus PCC 7942. We ultimately succeeded in producing 400 mg/L of DOI in S. elongatus without using a carbon source. DOI production by cyanobacteria represents a novel and efficient approach for producing benzenoids from G6P synthesized by photosynthesis.

FDG-PET/CT detection of very early breast cancer in women with breast microcalcification lesions found in mammography screening

International Nuclear Information System (INIS)

Peng, Nang-Jing; Chou, Chen-Pin; Pan, Huay-Ben; Chang, Tsung-Hsien; Hu, Chin; Chiu, Yu-Li; Fu, Ting-Ying; Chang, Hong-Tai

2015-01-01

To assess the efficacy of positron emission tomography/computed tomography with the glucose analogue 2-[ 18 F]fluoro-2-deoxy-D-glucose (FDG-PET/CT) in Taiwanese women with early breast cancer detected by mammography screening. Dual-time-point imaging of whole-body supine and breast prone scans using FDG-PET/CT were performed sequentially in the pre-operative stage. A total of 11,849 patients underwent screening mammography, of whom 1,209 (10.2%) displayed positive results. After further investigation, 54 patients underwent FDG-PET/CT. Post-operative pathology examinations revealed malignancies in 26 lesions, including invasive breast cancer in 11 cases and non-invasive breast cancer in 15 cases, as well as benign disease in 30 lesions. The FDG-PET/CT findings from the whole-body scans were positive for 9 of 11 invasive breast cancers (81.8%) and 3 of 15 non-invasive cancers (20%), and they were negative for all benign lesions. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of FDG-PET/CT with whole-body supine imaging were 46.2%, 100%, 100% and 68.2%, respectively. Breast prone imaging revealed another patient with ductal carcinoma in situ, increasing the sensitivity to 50%. Importantly, positive PET findings were significantly correlated with tumour histology (P = 0.006), tumour size (P = 0.039) and Ki-67 expression (P = 0.011). FDG-PET/CT with whole-body scanning demonstrated high sensitivity to invasive breast cancer, limited sensitivity to non-invasive breast cancer, and high specificity for breast cancer. FDG-PET/CT might be useful for differentiating tumour invasiveness. However, the good PPV but poor NPV do not allow the physician to discard the biopsy.

Fabrication, characterization, in vitro drug release and glucose uptake activity of 14-deoxy, 11, 12-didehydroandrographolide loaded polycaprolactone nanoparticles

Directory of Open Access Journals (Sweden)

Nagalakshmi Kamaraj

2017-07-01

Full Text Available Biodegradable polymer based novel drug delivery systems brought a considerable attention in enhancing the therapeutic efficacy and bioavailability of various drugs. 14-deoxy 11, 12-didehydro andrographolide (poorly water soluble compound loaded polycaprolactone (nano-DDA was synthesized using the solvent evaporation technique. Nano-DDA was characterized by scanning electron microscopy (SEM and dynamic light scattering (DLS studies. Fourier Transform InfraRed Spectroscopy (FTIR was used to investigate the structural interaction between the drug and the polymer. Functional characterization of the formulation was determined using drug content, cellular uptake and in vitro drug release. 2-deoxy-D-[1-3H] glucose uptake assay was carried out to assess the antidiabetic potential of nano-DDA in L6 myotubes. The nano-DDA displayed spherical shape with a smooth surface (252.898 nm diameter, zeta potential, encapsulation and loading efficiencies of −38.9 mV, 91.98 ± 0.13% and 15.09 ± 0.18% respectively. No structural alteration between the drug and the polymer was evidenced (FTIR analysis. Confocal microscopy studies with rhodamine 123 loaded polycaprolactone nanoparticles (Rh123-PCL NPs revealed the internalization of Rh123-PCL NPs in a time dependent manner in L6 myoblasts. A dose dependent increase in glucose uptake was observed for nano-DDA with a maximal uptake of 108.54 ± 1.42% at 100 nM on L6 myotubes, thereby proving its anti-diabetic efficacy. A biphasic pattern of in vitro drug release demonstrated an initial burst release at 24 h followed by a sustained release for up to 11 days. To conclude, our results revealed that nano-DDA formulation can be a potent candidate for antidiabetic drug delivery.

Biosynthesis of the sesquiterpene germacrene D in Solidago canadensis: 13C and (2)H labeling studies.

Science.gov (United States)

Steliopoulos, Panagiotis; Wüst, Matthias; Adam, Klaus-Peter; Mosandl, Armin

2002-05-01

The biogenetic origin of the isoprenoid building blocks of the sesquiterpene germacrene D was studied in Solidago canadensis. Feeding experiments were carried out with 1-[5,5-D(2)]deoxy-D-xylulose-5-phosphate (D(2)-DOXP), [5-13C]mevalonolactone (13C-MVL) and [1-13C]-D-glucose. The hydrodistillate of a cut shoot fed with D(2)-DOXP was investigated by enantio-MDGC-MS and the volatile fraction of a shoot supplied with 13C-MVL was examined by GC-C-IRMS. The incorporation of [1-13C]-D-glucose was analyzed by quantitative 13C NMR spectroscopy after isolation of germacrene D from the essential oil. Our labeling studies revealed that the biosynthesis of the C-15 skeleton of sesquiterpene germacrene D in Solidago canadensis proceeds predominantly via the methylerythritol phosphate pathway.