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The Use of Microwaves for the Automated Production of Radiopharmaceuticals

  • Sharon Stone-Elander
  • Nils Elander

Abstract

The first reports of the use of microwaves to effect chemical transformations for use in PET radiochemistry appeared in 1982–1984. These applications were gas phase transformations in microwave discharges to produce radiolabelling precursors and were reported by the Cyclotron Corporation in Berkeley1, the Brookhaven National Laboratory in New York1,2 and the Kitasato University in Kanagawa, Japan3. The PET group in St. Louis, Mo. broke the barrier for using microwaves in liquid phase radiolabelling reactions4 in 1987 with their report on the use of a microwave oven to reduce radiolabelling times and increase end-of-synthesis yields in nucleophilic radiofluorinations and- iodinations. The number of papers presented using microwaves in PET radiochemistry since 1987 parallels the increasing number of applications reported in other areas of chemistry (for reviews see Abramovitch5 and Mingos and Baghurst6) and reflects the growing realization that this technique can help radiochemists speed up difficult synthetic transformations requiring long reaction times and stringent conditions. Research groups at the Liége University in Belgium, Groningen University Hospital in the Netherlands, Karolinska Institute in Sweden, Kettering Medical Center in Ohio, University of Tennesee at Knoxville and Chedoke-McMaster Hospital in Hamilton, Ontario have reported using microwaves in radiotracer syntheses. This technology is expected to spread even more as more user-adapted microwave devices become available.

Keywords

Methyl Iodide Microwave Field Microwave Treatment Microwave Cavity Diethyl Oxalate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Straatman M.G., Schlyer D.J., and Chasko J. Synthesis of F18-fluorine gas from no carrier added F18-HF. J. Label. Cmpds.9. 19: 1372 (1982).Google Scholar
  2. 2.
    Fernen R.A., Schlyer D.J., Wieland B.W., and Wolf A.P. On-line production of 13N-nitrogen gas from a solid enriched l3C-target and its application to 13N-ammonia synthesis using microwave radiation. Int. J. Appl. Radiat, Isot. 34: 897 (1983).CrossRefGoogle Scholar
  3. 3.
    Niisawa K., Ogawa K., Saito J., Taki K., Karasawa T., and Nozaki T. Production of no-carrier-added 11C-carbon disulfide and +C-hydrogen cyanide by microwave discharge Int. J. Appl. Radiat, Isot. 35: 29 (1984).CrossRefGoogle Scholar
  4. 4.
    Hwang D.R., Moerlein S.M., Lang L., and Welch M.J. Application of microwave technology to the synthesis of short-lived radiopharmaceuticals. J. Chem. Soc., Chem. Commun. 1799 (1987).Google Scholar
  5. 5.
    Abramovitch R.A. Applications of microwave energy in organic chemistry. A review. Organic Preparations and Procedures International 23: 683 (1991).CrossRefGoogle Scholar
  6. 6.
    Mingos D.M.P. and Baghurst D.R. Applications of microwave dielectric heating effects to synthetic problems in chemistry. Chem. Soc. Rev. 20: 1 (1991).CrossRefGoogle Scholar
  7. 7.
    Baghurst D.R. and Mingos D.M.P. Superheating effects associated with microwave dielectric heating. J. Chem. Soc., Chem. Commun. 614 (1992).Google Scholar
  8. 8.
    Ng K-H Microwave ovens: mapping the electrical field distribution. Med. Lab. Sci. 48: 189(1991).PubMedGoogle Scholar
  9. 9.
    Stone-Elander S. and Elander N. Microwave cavities: some parameters affecting their use in radiolabelling reactions. Appl. Radiat, Isot. 42: 885 (1991).CrossRefGoogle Scholar
  10. 10.
    Stone-Elander S.A. and Elander N. Microwave cavity: use in 11C-alkylations. J. Label. Cmpds. Ratiopharm. 32: 154 (1993).Google Scholar
  11. 11.
    Zijlstra S., de Groot T.J., Kok L.P., Visser G.M., and Vaalburg W. Behavior of reaction mixtures under microwave conditions: use of sodium salts in microwave- induced N-[18F]fluoroalkylations of apomorphine and tetralin derivatives. J. Org. Chem. 58: 1643 (1993).CrossRefGoogle Scholar
  12. 12.
    Stone-Elander S.A. and Elander N. Fast chemistry in microwave fields: nucleophilic [18F]radiofluorinations of aromatic molecules. Appl. Radiat. Isot. 44 889 (1993).CrossRefGoogle Scholar
  13. 13.
    Hwang D.-R., Dence C.S., Gong J., and Welch M.J. A new procedure for labeling alkylbenzenes with [18F]fluoride. Appl. Radiat. Isot. 42: 1043 (1991).CrossRefGoogle Scholar
  14. 14.
    Hwang D.-R., Banks W.R., and Mantil J.C. A general method for preparing [l8F]fluorophenethylamines, synthesis of 4-[18F]fluorofentanyl. J. Label. Cmpds. Radiopharm. 32: 328 (1993).Google Scholar
  15. 15.
    Banks W.R., Hwang D.-R., Borchert R.D., and Mantil J.C. Production optimization of a afunctional radiopharmaceutical intermediate: fluorine-18 fluoroacetophenone. J. Label. Cmpds. Radiopharm. 32: 101 (1993).Google Scholar
  16. 16.
    Hwang D.R., Moerlein S.M., Dence C.S., and Welch M.J. Microwave-facilitated synthesis of [18F]spiperone. J. Label. Cmpds. Radiopharm. 26: 391 (1989).CrossRefGoogle Scholar
  17. 17.
    Banks W.R., Hwang D.-R., Borchert R.D., and Mantil J.C. A new approach to the production of NCA fluorine-18 labelled butyrophenone neuroleptic agents. Synthesis of γ-iodo-p-[18F]-fluorobutyrophenone using diiodosilane. J. Label. Cmpds Radiopharm. 32: 333 (1993)Google Scholar
  18. 18.
    Hwang D.R., Dence C.S., McKinnon Z.A., Mathis C.J., and Welch M.J. Positron labeled muscarinic acetylcholine receptor antagonist: 2- and 4-[l8F]fluorodexetimide Nucl. Med. Biol. 18: 247 (1991).Google Scholar
  19. 19.
    Plenevaux A., Lemaire C., Palmer A.J., Damhaut P., and Comar D. Synthesis of non-activated 18F-fluorinated aromatic compounds through nucleophilic substitution and decarboxylation reactions. Appl. Radiat. Isot. 43: 1035 (1992).CrossRefGoogle Scholar
  20. 20.
    Gong J.L., Dence C.S., and Welch M.J. Synthesis of [18F]fluorobepridil, a positron labeled calcium antagonist. J. Label. Cmpds. Radiopharm. 32: 314 (1993).Google Scholar
  21. 21.
    Hwang D.R., Moerlein S.M., and Welch M.J. No-carrier-added F-18 for NO2 aromatic nucleophilic sustitution reactions of nitrocinnamic acid derivatives. J. Nucl. Med. 30: 1757 (1989).Google Scholar
  22. 22.
    Lemaire C., Cantineau R., Guillaume M., Plenevaux A., and Christiaens L. Fluorine-18-altanserine: a radioligand for the study of serotonin receptors with PET: radiolabeling and in vivo biologic behavior in rats. J. Nucl. Med. 32: 2266 (1991).PubMedGoogle Scholar
  23. 23.
    Collier T.L., Goodman M.M., Kabalka G.W., and Longford C.P.D. Rapid microwave radiofluorination of (1R-2-exo-3-exo)-2-carbomethoxy-8-azabicyclo[3.2.1]octyl-3-N-(4′-[18F]fluoro-3′-nitrophenyl)carbamate: a potential PET cocaine receptor imaging agent. J. Nucl. Med. 33: 1025 (1992).Google Scholar
  24. 24.
    Chirakal R., Girard L., Firnau G., and Garnett E.S. Synthesis of 2-[18F]FDG using microwave radiation. J. Label. Cmpds.Radiopharm. 32: 123 (1993).Google Scholar
  25. 25.
    Thorell J.-O., Stone-Elander S., and Elander N. Use of a microwave cavity to reduce reaction times in radiolabelling with [=C]cyanide. J. Label. Cmpds.Radiopharm. 31: 207 (1992).CrossRefGoogle Scholar
  26. 26.
    Thorell J.-O., Stone-Elander S., and Elander N. Preparation of [11C]diethyl oxalate and [11C]oxalic acid and demonstration of their use in the synthesis of [11C]-2,3-dihydroxy-quinoxaline. J. Label. Cmpds. Radiopharm. in press (1993).Google Scholar
  27. 27.
    Stone-Elander S: A. & Elander N. Radiochemistry in microwave fields: 11C-alkylations. J. Nucl. Med. 33: 1026 (1992).Google Scholar
  28. 28.
    Goodman M.M., Collier T.L., Kabalka G.W., and Longford C.P.D. Synthesis of carbon-11 labeled (1R-2-exo-3-exo)-2-carbomethoxy-8-methyl-8-azabicyclo-[3.2.1]octyl-3-N-(3′-nitrophenyl)carbamate as a potential PET dopamine receptor imaging agent. J. Label. Cmpds. Radiopharm. 32: 286 (1993).Google Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Sharon Stone-Elander
    • 1
    • 2
  • Nils Elander
    • 3
  1. 1.Karolinska PharmacySweden
  2. 2.Clinical NeurophysiologyKarolinska InstituteSweden
  3. 3.Manne Siegbahn Institute of PhysicsStockholmSweden

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