3-Fluoro-3-deoxyglucose

PET has been gaining in popularity as a result of its enhanced sensitivity and resolution with respect to SPECT at the millimetre scale, allowing clinicians to study drug distribution in vivo (10). Indeed, it is estimated that by 2010 there will be approximately two million PET scans per year, of which the majority will image the metabolism of the 18F-labeled fluoro-deoxyglucose (FDG) (11). The increased sensitivity in turn reduces the concentration of the administered radiopharmaceutical required to 10 8-10 10M. The much lower concentrations of administered radioactive probe employed reduce the overall... 

C.S. Yap, J. Czemin, M.C. Fishbein, R.B. Cameron, C. Schiepers, M.E. Phelps, W.A. Weber, Evaluation of thoracic tumors with F-fluorothymidine and F-fluoro-deoxyglucose-positron emission tomography. Chest 129 (2006) 393-401. 

P. Zanzonico, J. Campa, D. Polycarpe-Holman, G. Forster, R. Finn, S. Larson, J. Humm, C. Ling, Animal-specific positioning molds for registration of repeat imaging studies Comparative microPET imaging of F18-labeled fluoro-deoxyglucose and fluoro-misonidazole in rodent tumors, Nucl. Med. Biol. 33 (2006) 65-70. 

Thallium-201 SPECT and fluoro-deoxyglucose (FDG)PET are both used to help differendate residual brain tumor and brain tumor recuiTence from racUadon necrosis. Thallium-201 SPECT has been found to be Just as good or even better for tumor detecdon than FDG PET (Kahn et al., 1994 Maria et al., 1998 Stokkel et al., 1999). Thallium-201 SPECT can also be udhzed to help cUfferendate lymphoma from toxoplasmosis which is an important quesdon in immunocompromised... 

F-2-FDG is used primarily for the study of metabohsm in the brain and heart and for the detection of epilepsy and various tumors. In metabolism, 18F-2-FDG is phosphorylated by hexokinase to 2-FDG-6-phosphate which is not metabolized further. It should be noted that 3-fluoro-deoxyglucose (3-FDG) is not phosphorylated and hence is not trapped and essentially eliminated rapidly from the cell. This is why 3-FDG is not used for metabolic studies. 

Joanna S. Fowler (NAS) is a senior chemist at the U.S. Department of Energy s Brookhaven National Laboratory. Dr. Fowler has been a major contributor to brain research and the study of diseases such as addiction, which she has investigated using the imaging technique positron emission tomography (PET). In 1976 she and her colleagues synthesized 18F-fluoro-deoxyglucose, a radiotracer used in PET. Dr. Fowler earned a B.S. from the University of South Florida and a Ph.D. from the University of Colorado, Boulder. 

Bender, H., Kerst, J., Palmedo, H., Schomburg, A., Wagner, U., Ruhlmann, J., and Biersack, H. J. (1997). Value of (18)fluoro-deoxyglucose positron emission tomography in the staging of recurrent breast carcinoma, Anri-cancer Research, 17 1687-1692. 

Jacob R, Welkoborsky HJ, Mann WJ, Jauch M, Amadee R. [Fluorine-18]fluoro-deoxyglucose positron emission tomography, DNA ploid and growth fraction in squamous-cell carcinomas of the head and neck. ORL J Otorhinolaryngol Relat... 

Raj endran JG, Mankoff DA, O Sullivan F, Peterson LM, Schwartz DL, Conrad EU, Spence AM, Muzi M, Farwell DG, Krohn KA. Hypoxia and glucose metabolism in malignant tumors evaluation by [ F]fluoromisonidazole and [ F]fluoro-deoxyglucose positron emission tomography imaging. Clin Cancer Res 2004 10 2245-2252. 

Di Chiro G, DeLaPaz RL, Brooks RA, et al. (1982) Glucose utilization of cerebral gliomas measured by [18F]fluoro-deoxyglucose and positron emission tomography. Neurology 32 1323-9... 

Volkow ND, Gillespie H, Mullani N, Tancredi L, Grant C, Ivanovic M, Hollister L. (1991). Cerebellar metabolic activation by delta-9-tetrahydrocannabinol in human brain a study with positron emission tomography and 18F-2-fluoro-2-deoxyglucose. Psychiatry Res. 40(1) 69-78. 

The most useful and important positron emitting radiopharmaceuticals, 2-deoxy-2-[ F]fluoro-D-deoxyglucose [ F]FDG, is prepared in a two-step... 

Marwick TH, Nemec JJ, Lafont A, Salcedo EE, MacIntyre WJ. Prediction by postexercise fluoro-18 deoxyglucose positron emission tomography of improvement in exercise capacity after revascularization. Am J Cardiol 1992 69 854-859... 

Rees JH, Hain SF, Johnson MR, Hughes RA, Costa DC, Ell PJ, et al. The role of [18F] fluoro-2-deoxyglucose-PET scanning in the diagnosis of paraneoplastic neurological disorders. Brain 2001 124(Pt. 11) 2223-2231. 

F-2-fluoro-2-deoxyglucose (2-FDG) is normally produced in places where a cyclotron is locally available. Its molecular formula is CsHn FOs with molecular weight of 181.3 daltons. 18F-2-FDG can be produced by electrophilic substitution with 18F-fluorine gas or nucleophilic displacement with 18F-fluoride ions. The radiochemical yield is low with the electrophilic substitution, so the nucleophilic displacement reaction has become the method of choice for 18F-FDG synthesis. Deoxyglucose is labeled with 18F by nucleophilic displacement reaction of an acetylated sugar derivative followed by hydrolysis (Hamacher et al, 1986). In nucleophilic substitution, a fluoride ion reacts to fluorinate the sugar derivative. A solution of 1,3,4,6-tetra-O-acetyl-2-0-trifluoromethane-sulfonyl-/ -D-mannopyranose in anhydrous acetonitrile is added to a dry residue of 18F-fluoride containing aminopolyether (Kryptofix 2.2.2) and potassium carbonate (Fig. 8.1). Kryptofix 2.2.2 is used as a catalyst to enhance the reactivity of the fluoride ions. The mixture is heated... 

Figure 8.1. Schematic synthesis of 18F-2-Fluoro-2-deoxyglucose (FDG). (Reprinted with the permission of The Cleveland Clinic Center for Medical Art Photography 2009. All Rights Reserved)...

A widely used molecular probe in PET imaging is the glucose mimic 2-deoxy-[ F]fluoro-D-deoxyglucose (FDG), which has been snccessfiilly employed in neurological, cardiovascular and oncology investigations. This probe has a relatively long half-life of 109 min, which makes its prodnction/utilization in hospitals more practical than probes based on other radionnclides with shorter half-lives. 

Figure 13.3 Structure of 2-deoxy-[ F]fLuoro-D-deoxyglucose and schematic representation of its mode of action...

Chloro-2-deoxyarabinose D-form Di-Et dithioacetal, C-74 2-Chloro-2-deoxyascorbic acid L-form, C-78 2-Chloro-2-deoxyglucose D-form, C-85 2-Chloro-2-deoxylyxose a-D-Pyranose-/orw, C-95 2-Chloro-2-deoxyxylose D-Pyranose-/orm, C-108 2-Deoxy-2,2-difluoro-flrfl6mo-hexose D-form, D-55 2 -Deoxy-2 -fluoroadenosine, D-63 1 -(2-Deoxy-2-fluoro- p-D-arabinofuranosyl)uracil, D-66 2-Deoxy-2-fluoroarabinose a-L-Furanose-/<3rm 1,3,5-Tribenzoyl, D-68 2-Deoxy-2-fluoroarabinose p-D-Furanose-/orm, D-68 2-Deoxy-2-fluoroarabinose a-D-Pyranose- brm, D-68 2-Deoxy-2-fluoroarabinose p-D-Pyranoae-/orm, D-68 2-Deoxy-2-fluoroarabinose D-form, D-68 2 -Deoxy-2 -fluoro-ara -aristeromycin, D-70 2-Deoxy-2-fluoroascorbic acid L-form, D-71 2 -Deoxy-2 -fluorocytidine, D-72... 

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