Seminars in Nuclear Medicine
Volume 32, Issue 1 , Pages 6-12 , January 2002

Initial and subsequent approach for the synthesis of 18FDG

This article is dedicated to the memory of Alfred P. Wolf, whose vision and contributions to the development of 18FDG, to the advancement of radiotracer chemistry, and to the training of scientists have had an enormous, worldwide impact on the field of nuclear medicine.

  • Joanna S. Fowler

      Affiliations

    • Corresponding Author InformationAddress reprint requests to Joanna S. Fowler, PhD, Chemistry Department, Brookhaven National Laboratory, Upton, NY 11973.
    • ,
  • Tatsuo Ido

References 

  1. Ido T, Wan C-N, Casella V, et al. Labeled 2-deoxy-D-glucose analogs, 18F-labeled 2-deoxy-2-fluoro-D-glucose, 2-deoxy-2-fluoro-D-mannose and 14C-2-deoxy-2-fluoro-D-glucose. J Label Compounds Radiopharm. 1978;14:171–183
  2. Reivich M, Kuhl D, Wolf A, et al. The [18F]fluorodeoxyglucose method for the measurement of local cerebral glucose utilization in man. Circ Res. 1979;44:127–137
  3. Sokoloff L. Mapping of local cerebral functional activity by measurement of local cerebral glucose utilization with [14C]deoxyglucose. Brain. 1979;102:653–668
  4. Gallagher BM, Ansari A, Atkins H, et al. Radiopharaceuticals XXVII: 18F-labeled 2-deoxy-2-fluoro-D-glucose as a radiopharmaceutical for measuring regional myocardial glucose metabolism in vivo: Tissue distribution and imaging studies in animals. J Nucl Med. 1977;19:990–997
  5. Som P, Atkins HL, Bandoypadhyay D, et al. A fluorinated glucose analog, 2-fluoro-2-deoxy-D-glucose (F-18): Nontoxic tracer for rapid tumor detection. J Nucl Med. 1980;21:670–675
  6. Fowler JS, Wolf AP. 2-deoxy-2-[18F]fluoro-D-glucose for metabolic studies: Current status. Appl Radiat Isot. 1986;37:663–668
  7. Washington DC Garley SJ, Holden JE, DeGrado TR, et al. Preparation of fluorine-18 deoxyfluorohexoses for metabolism and transport studies. In: Taylor NF editors. Fluorinated carbohydrates: Chemical and biochemical aspects. Symp Series 374. Americal Chemical Society; 1988;p. 156–175
  8. Beuthien-Baumann B, Hamacher K, Oberdorfer F, et al. Preparation of fluorine-18 labelled sugars and derivatives and their application as tracer for positron-emission-tomography. Carbohydr Res. 2000;327:107–118
  9. Sols A, Crane RA. Substrate specificity of brain hexokinase. J Biol Chem. 1954;210:581–595
  10. MacGregor RR, Fowler JS, Wolf AP, et al. A synthesis of 11C-2-deoxy-D-glucose for regional metabolic studies. J Nucl Med. 1981;22:800–803
  11. Kuhl DE, Hoffman EJ, Phelps ME, et al. Design and application of the Mark IV scanning system for radionuclide computed tomography of the brain. In: International Atomic energy Agency Symposium on medical Radionuclide Imaging. Los Angeles, CA. Medical Radionuclide Imaging. vol 1:Vienna: IAEA; 1977;p. 309–320Oct 25–29, 1976
  12. Bessell EM, Foster AB, Westwood JH. The use of deoxyfluoro-D-glucopyranoses and related compounds in a study of yeast hexokinase specificity. Biochem J. 1972;128:199–204
  13. Weber G. Enzymology of cancer cells. N Eng J Med. 1977;296:541–551
  14. Gallagher BM, Fowler JS, Gutterson NI, et al. Metabolic trapping as a principle of radiopharmaceutical design: Some factors responsible for the biodistribution of [18F]2-deoxy-2-fluoro-D-glucose. J Nucl Med. 1978;19:1154–1161
  15. Silverman M. Specificity of monosaccharide transport in the dog kidney. Am J Physiology. 1970;218:743–750
  16. Coleman RE. FDG imaging. Nucl Med Biol. 2000;27:689–690
  17. Adamson J, Foster AB, Hall LD, et al. Fluorinated carbohydrates. Part III. 2-deoxy-2-fluoro-D-glucose and 2-deoxy-2-fluoro-D-mannose. Carbohydr Res. 1970;15:351–359
  18. Pacak J, Tocik Z, Cerny M. Synthesis of 2-deoxy-2-fluoro-D-glucose. J Chem Soc Chem Comm. 1969;77:
  19. Barton DHR, Hesse RH, Markwell RE, et al. Fluorination at saturated carbon. 2. Direct fluorination of steroids. J Am Chem Soc. 1976;98:3036–3037
  20. Ido T, Wan C-N, Fowler JS, et al. Fluorination with F2. A convenient synthesis of 2-deoxy-2-fluoro-D-glucose. J Org Chem. 1977;42:2341–2342
  21. Lambrecht R, Wolf AP. Cyclotron and short-lived halogen isolopes for radiopharmaceutical applications. In: Radiopharmaceuticals and Labeled Compounds. volume 1:Vienna: International Atomic Energy Agency; 1973;p. 275–290
  22. Fowler JS, Finn RD, Lambrecht RM, et al. The synthesis of 5-fluorouracil-18F. J Nucl Med. 1973;14:63–64
  23. Bessell EM, Courtenay VD, Foster AB, et al. Some in vivo and in vitro antitumor effects of the deoxyfluoro-D-gluco-pyranoses. Eur J Cancer. 1973;9:463–470
  24. Jones SC, Alavi A, Christman D, et al. The radiation dosimetry of [F-18]-2-fluoro-2-deoxy-D-glucose in man. J Nucl Med. 1982;23:613–617
  25. Bida GT, Satyamurthy N, Barrio J. The synthesis of 2-[18F]fluoro-2-deoxy-D-glucose using glycols: A reexamination. J Nucl Med. 1984;25:1327–1334
  26. Braun AR, Carson RE, Adams HR, et al. A kinetic comparison of [18F]2-fluoro-2-deoxymannose using positron emission tomography. Nucl Med Biol. 1994;6:857–863
  27. Casella V, Ido T, Wolf AP, et al. Anhydrous F-18 labeled elemental fluorine for radiopharmaceutical preparation. J Nucl Med. 1980;21:750–757
  28. Ruth TJ, Wolf AP. Absolute cross sections for the production of 18F via the 18O(p,n) 18F reaction. Radiochim Acta. 1979;26:21–24
  29. Wieland BW, Hendry GO, Schmidt DG, et al. Efficient small-volume 18O-water targets for producing 18F fluoride with low energy protons. J Label Compounds Radiopharm. 1986;23:1205–1207
  30. Kilbourn MR, Hood JT, Welch MJ. A simple 18O-water target for 18F production. Int J Appl Radiat Isot. 1984;35:599–602
  31. Schlyer DJ, Bastos MAV, Alexoff A, et al. Separation of [18F]fluoride from [18O]water using anion exchange resin. Appl Radiat Isot. 1990;41:531–533
  32. Hamacher K, Coenen HH, Stocklin G. Efficient stereospecific synthesis of NCA 2-[18F]fluoro-2-deoxy-D-glucose using aminopolyether supported nucleophilic substitution. J Nucl Med. 1986;27:235–238
  33. Alexoff DL, Casati R, Fowler JS, et al. Ion chromatographic analysis of high specific activity 18FDG preparations and detection of the chemical impurity in 2-deoxy-2-chloro-D-glucose. Appl Radiat Isot. 1992;43:1313–1322
  34. Satyamurthy N, Phelps ME, Barrio JR. Electronic generators for the production of positron-emitter labeled radiopharmaceuticals; Where would PET be without them?. Clin Positron Imaging. 1999;2:233–252
  35. Moerlein SM, Brodack JW, Siegel BA, et al. Elimination of contaminant kryptofix 2.2.2 in the routine production of 2-[18F]fluoro-2-deoxy-D-glucose. Appl Radiat Isot. 1989;40:741–743
  36. Alexoff DL, Fowler JS, Gatley SJ. Removal of the 2.2.2 cryptands (kryptofix 2.2.2) from 18FDG by cation exchange. Appl Radiat Isot. 1991;42:1189–1193
  37. Ferrieri RA, Schlyer DJ, Alexoff DL, et al. Direct analysis of kryptofix 2.2.2 in 18FDG by gas chromatography using a nitrogen-selective detector. Nucl Med Biol. 1993;20:367–369
  38. Chaly T, Dahl JR. Thin layer chromatographic detection of kryptofix 2.2.2 in the routine synthesis of [18F]2-fluoro-2-deoxy-D-glucose. Nucl Med Biol . 1989;16:385–387
  39. Yuasa M , Yoshida H , Hara T . Computer-controlled synthesis of [18F]FDG by the tettrabutylammonium method: Achievement of high yield, purity, reproducibility, reliability, and safety . Appl Radiat Isot . 1997;48:201–205
  40. Brodack JW , Dence CS , Kilbourn MR , et al.   Robotic production of 2-deoxy-2-[18F]fluoro-D-glucose: A routine method of synthesis using tetrabutylammonium [18F]fluoride . Appl Radiat Isot . 1988;39:699–703
  41. Toorongian SA , Mulholland GK , Jewett DM , et al.   Routine production of 2-deoxy-2-[18F]fluoro-D-glucose by direct nucleophilic exchange on a quaternary 4-aminopyridinium resin . Int J Radiat Appl Instrum B . 1990;17:273–279
  42. Ohsaki K , Endo Y , Yamazaki S , et al.   Polymer-supported catalysts for on-column preparation of 2-deoxy-2-[18F]fluoro-D-glucose . Appl Radiat Isot . 1998;49:373–378
  43. Mulholland GK. Simple rapid hydrolysis of acetyl protecting groups in the FDG synthesis using cation exchange resins. Nucl Med Biol. 1995;22:19–23
  44. Varelis P, Barnes RK. Epimerization of 2-deoxy-2-[18F]fluoro-D-glucose under basic conditions. A convenient method for the preparation of 2-deoxy-2-[18F]fluoro-D-mannose. Appl Radiat Isot. 1996;47:731–733
  45. Meyer G-J, Matzke KH, Hamacher K, et al. The stability of 2-[18F]fluoro-deoxy-D-glucose towards epimerization under alkaline conditions. Appl Radiat Isot. 1999;51:37–41
  46. Fowler JS, Volkow ND, Wang G-J, et al. PET and drug research and development. J Nucl Med. 1990;40:1154–1163
  47. Machado De Domenech EE, Sols A. Specificity of hexokinases towards some uncommon substrates and inhibitors. FEBS Lett. 1980;119:174–176
  48. Shiue C-Y, Salvadori PA, Wolf AP, et al. A new improved synthesis of 2-deoxy-2-[18F]fluoro-D-glucose from 18F-labeled acetyl hypofluorite. J Nucl Med. 1982;23:899–903
  49. Adam MJ. A rapid, stereoselective, high yielding synthesis of 2-deoxy-2-fluoro-D-hexopyranoses: Reaction of glycols with acetyl hypofluorite. J Chem Soc Chem Commun. 1982;730–732
  50. Diksic M, Jolly D. New high-yield synthesis of 18F-labeled 2-deoxy-2-fluoro-D-glucose. Int J Appl Radiat Isot. 1983;34:893–896
  51. Ehrenkaufer RE, Potocki JF, Jewett DM. Simple synthesis of F-18-labeled 2-fluoro-2-deoxy-D-glucose: Concise communication. J Nucl Med. 1984;25:333–337
  52. Jewett DM, Potocki JF, Ehrenkaufer RE. A gas-solid phase microchemical method for the synthesis of acetyl hypofluorite. J Fluorine Chem. 1984;24:477–484
  53. Shiue C-Y, To KC, Wolf AP. A rapid synthesis of 2-deoxy-2-fluoro-D-glucose from xenon difluoride suitable for labeling with 18F. J Label Compounds Radiopharm. 1983;20:157–162
  54. Sood S, Firnau G, Garnett ES. Radiofluorination with xenon difluoride. Int J Appl Radiat Isot. 1983;34:743–745
  55. Levy S, Elmaleh D, Livni E. A new method using anhydrous [18F]fluoride to radiolabel 2-[18F]fluoro-2-deoxy-D-glucose. J Nucl Med. 1982;23:918–922
  56. Levy S, Livni E, Elmaleh D, et al. Direct displacement with anhydrous fluoride of the C-2 trifluoromethanesulfonate of methyl 4,6-O-benzylidene-3-O-methyl-2-O-trifluoromethyl-sulphonyl-β-D-mannoside. J Chem Soc Chem Cornm. 1982;972–973
  57. Tewson TJ. Synthesis of no-carrier-added fluorine-18 2-fluoro-2-deoxy-D-glucose. J Nucl Med. 1983;24:718–721
  58. Tewson TJ. Cyclic sulfur esters as substrates for nucleophilic substitution. A new synthesis of 2-deoxy-2-fluoro-D-glucose. J Org Chem. 1983;48:3507–3510
  59. (abstr) Tewson TJ, Soderlind M. I-Propenyl-4,6-O-benzylidene-β-mannopyranoside-2,3-cyclic sulfate: A new substrate for the synthesis of [F-18]-2-deoxy-2-fluoroglucose. J Nucl Med. 1985;26:129
  60. Szarek W, Hay GW, Perlmutter MM. A rapid stereospecific synthesis of 2-deoxy-2-fluoro-D-glucose using fluoride ion. J Chem Soc Chem Comm. 1982;1253–1254
  61. Beeley PA, Szarek WA, Hay GW, et al. A synthesis of 2-deoxy-2-[18F]fluoro-D-glucose using accelerator-produced 18F-fluoride ion generated in a water target. Can J Chem. 1984;62:2709–2711

+ This research was performed in part at Brookhaven National Laboratory under contract DE-AC02-98CH10886 with the US Department of Energy and was supported by its Office of Biological and Environmental Research and by the National Institutes of Health (NS-15380).

PII: S0001-2998(02)80036-8

doi: 10.1053/snuc.2002.29270

Seminars in Nuclear Medicine
Volume 32, Issue 1 , Pages 6-12 , January 2002

Article Tools