Skip to main content
SpringerLink
Log in

Fluorine-18 Labeling of Radiopharmaceuticals for PET Studies: Main Aspects and Problems Encountered in Chemical Syntheses

  • Chapter
Chemists’ Views of Imaging Centers

Abstract

Positron emission tomography has considerably developed during the past ten years and has proved to be the only original quantitative method appropriate to the study of the in vivo working of the brain, a field quite difficult to approach by other imaging techniques. Beside the considerable technical advances in positron tomographs, the recent progress in the radiochemistry of short-lived radionuclides have, to a large extent, contributed to the development of this functional imaging technique. Now being used in many research centers, PET studies with a labeled molecule known as radiopharmaceutical, carefully selected in respect of its biochemical properties and its in vivo biological behaviour, allow the quantitative determination of numerous physiological parameters (Phelps et al., 1986).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Adam, M.J., Ruth, T.J., Grierson, J.R., Abeysekera, B., Pate, B.D., 1986, Routine synthesis of L-[18F]6-fluorodopa with fluorine-18 acetyl hypofluorite. J. Nucl Med, 27, 1462.

    PubMed  CAS  Google Scholar 

  • Adam, M.J., Jivan S., 1988, Synthesis and purification of L-6-[18F]fluorodopa, Appl Radiat hot. 39: 1203.

    Article  CAS  Google Scholar 

  • Cantineau, R., Damhaut, P., Plenevaux, A.. Lemaire, C., Guillaume, M., 1991, Synthesis and preliminary animal studies of [123I]iodotropapride: a cerebral dopamine D2 receptor ligand, J. Labelled Compd. Radiopharm. 30: 360.

    Google Scholar 

  • Chaly, T., Diksic, M., 1986, High yield synthesis of 6-[18F]fluoro-L-dopa by regioselective fluorination of protected L-dopa with [18F]acetylhypofluorite. J. Nucl. Med. 27:1896.

    PubMed  CAS  Google Scholar 

  • Chakraborty, P.K., Kilbourn, M.R., 1991, Oxidation of substituted 4-fluorobenzaldehydes: application to the no-carrier-added syntheses of 4-[18F]fluoroguaiacol and 4-[18F]fluorocatechol, Appl. Radiat. Isot. 42: 673.

    Article  CAS  Google Scholar 

  • Chirakal, R., Firnau, G., Couse, J., Garnett E.S., 1984, Radiofluorination with 18F-labelled acetyl hypofluorite: [18F]L-6-fluorodopa. Int. J. Appl. Rod. hot. 35: 651.

    Article  CAS  Google Scholar 

  • Chirakal, R., Firnau, G., Garnett, E.S., 1986, High yield synthesis of 6-[18F]fluoro-L-dopa. J. Nucl. Med. 27: 417.

    PubMed  CAS  Google Scholar 

  • Coenen, H.H., Klatte, B., Knöchel, A., Schüller, M., Stöcklin, G., 1986, Preparation of N.C.A. [17-18F]-fluoroheptadecanoic acid in high yields via aminopolyether supported, nucleophilic fluorination. J. Labelled Compd Radiopharm. 23, 455.

    Article  CAS  Google Scholar 

  • Coenen, H.H., Franken, K., Kling, P., Stöcklin G., 1988, Direct electrophilic radiofluorination of phenylalanine, tyrosine and dopa, Appl. Radiat. Isot. 39:1243.

    Article  CAS  Google Scholar 

  • Coenen, H.H., Kling, P., Stöcklin, G., 1989, Cerebral metabolism of L-2-[18F]fluorotyrosine, a new PET tracer of protein synthesis, J. Nucl. Med. 30:1367.

    PubMed  CAS  Google Scholar 

  • Coenen, H.H., 1993, Biochemistry and evaluation of fluoroamino acids, in “PET studies on amino acid metabolism and protein synthesis,” B.M. Mazoyer, W.D. Heiss, D. Comar, ed., Kluwer Academic Publishers, Dordrecht.

    Google Scholar 

  • Crouzel, C., Guillaume, M., Barré, L., Lemaire, C., Pike, V.W., 1992, Ligands and tracers for PET studies of the 5-HT system-Current status, Nucl. Med. Biol. 19:857

    CAS  Google Scholar 

  • Crouzel, C., Clark, C., Brihaye, C., Långström, B., Lemaire, C., Meyer, G.J., Nebelling, B. and Stone Elander, S., 1993, Radiochemistry automation for PET, in: “Radiopharmaceuticals for Positron Emission Tomography- Methodological aspects,” G. Stöcklin and V.W. Pike, ed„ Kluwer academic publishers, Dordrecht (in press).

    Google Scholar 

  • Diksic, M., Farrokhzad, S., 1985, New synthesis of fluorine-18-labelled 6-fluoro-L dopa by cleaving the carbon-silicon bond with fluorine. J. Nucl. Med. 26:1314.

    PubMed  CAS  Google Scholar 

  • Damhaut, P., Cantineau, R., Lemaire, C., Plenevaux, A., Christiaens, L, Guillaume, M., 1992, 2- and 4-[18F]fluorotropapride, two specific D2 receptor ligands for positron emission tomography: n.c.a; syntheses and animal studies, Appl. Radiat. Isot. 43:1265.

    Article  CAS  Google Scholar 

  • Ding, Y.-S., Shiue, C.-Y., Fowler, J. S., Wolf, A. P., Plenevaux A, 1990, No-carrier-added (N.C.A.) aryl [18F]fluorides via the nucleophilic aromatic substitution of electron-rich aromatic rings. J. Fluorine Chem. 48:189.

    Article  CAS  Google Scholar 

  • Ding, Y.-S., Fowler, J.S., Gatley, S.J., Dewey, S. L., Wolf A. P., 1991, Synthesis of high specific activity (+)- and (-)-6-[18F]fluoronorepinephrine via the nucleophilic aromatic substitution reaction. J. Med. Chem. 34: 767.

    Article  PubMed  CAS  Google Scholar 

  • Fasth, K.J., Malmborg, P., Långström, B., 1991, Two syntetic routes for the asymmetric synthesis of [b-11C]amino acids with high enantiomeric purities. J. Labelled Compds Radiopharm. 30: 401.

    Google Scholar 

  • Firnau, G., Chirakal, R., Sood, S., Garnett, E.S., 1980, Aromatic fluorination with xenon difluoride: L-3,4-dihydroxy-6-fluoro-phenylalanine. Can. J. Chem. 58:1449.

    Article  CAS  Google Scholar 

  • Firnau, G., Chirakal, R., Garnett E.S., 1984, Aromatic radiofluorination with [18F]fluorine gas: 6-[18F]fluoro-L-dopa./Afac/Med. 25:1228.

    CAS  Google Scholar 

  • Firnau, G., Garnett, E.S., Chirakal, R., Sood, S., Nahmias, C., Schrobilgen G., 1986, [18F]fluoro-L-dopa for the in vivo study of intracerebral dopamine, Appl. Rad. Isot. 37: 669.

    Article  CAS  Google Scholar 

  • Garnett, E.S., Firnau, G., Nahmias C., 1983, Dopamine visualized in the basal ganglia of living man, Nature. 305:137.

    Article  PubMed  CAS  Google Scholar 

  • Guillaume, M., Luxen, A., Nebeling, B., Argentini, M., Clark, J. C., Pike V. W., 1991, Recommendations for fluorine-18 production. (EEC Task Group Report), Appl. Radiat, Isot. 42:749.

    Article  CAS  Google Scholar 

  • Ishiwata, K., Ishii, S.-I., Senda, M., Tsuchiya, Y., Tomimoto, K., 1993, Electrophilic synthesis of 6-[18F]fluoro-L-dopa: use of 4-O-pivaloyl-L-dopa as a suitable precursor for routine production, Appl. Radiat. Isot. 44:755.

    Article  CAS  Google Scholar 

  • Keinan, E., Perez, D., Sahai, M., Shvily, R., 1990, Diiodosilane. 2. A multipurpose reagent for hydrolysis and reductive iodination of ketals, acetals, ketones, and aldehydes. J. Org. Chem. 55: 2927.

    Article  CAS  Google Scholar 

  • Kilbourn, M. R., 1990, “Fluorine-18 labeling of radiopharmaceuticals”. National Academy Press, Washington.

    Google Scholar 

  • Lemaire, C., Guillaume, M., Christiaens L., 1989, Asymmetric synthesis of 6-[18F]fluoro-L-dopa via N.C.A. nucleophilic radiofluorination. J. Nucl. Med. 30:752.

    Google Scholar 

  • Lemaire, C., Guillaume, M., Cantineau, R., Plenevaux, A., Christiaens L., 1990, No-carrier-added regioselective preparation of 6-[18F]-fluoro-L-dopa, J. Nucl Med. 31:1247.

    PubMed  CAS  Google Scholar 

  • Lemaire, C., Guillaume, M., Cantineau, R., Plenevaux, A., Christiaens L., 1991a, An approach to the asymmetric synthesis of L-6-[18F]fluorodopa via nca nucleophilic fluorination. Appl. Radiat. Isot. 42: 629.

    Article  CAS  Google Scholar 

  • Lemaire, C., Damhaut, P., Plenevaux, A., Cantineau, R., Christiaens, I., and Guillaume, M., 1991b, Asymmetric synthesis of 4-[18F]fluoro-L-m-tyrosine via aromatic fluorination. J. Nucl. Med. 32: 935.

    Google Scholar 

  • Lemaire, C., Cantineau, R., Guillaume, M., Plenevaux, A., Christiaens, L., 1991c, Fluorine-18-altanserin: a radioligand for the study of serotonin receptors with PET: radiolabelling and in vivo biological behavior in rats, J. Nucl. Med. 32: 2266.

    PubMed  CAS  Google Scholar 

  • Lemaire, C., Damhaut, P., Cantineau, R., Plenevaux, A., Guillaume, M., 1991d, N.C.A. synthesis of an N-ω-[18F]-fluoroethyl analog of altanserine, a serotonin S2 receptor ligand, J. Labelled Compd. Radiopharm. 30:374.

    Google Scholar 

  • Lemaire, C., Damhaut, P., Plenevaux, A., Cantineau, R., Christiaens, L., Guillaume, M., 1992a, Synthesis of fluorine-18 substituted aromatic aldehydes and benzyl bromides, new intermediates for n.c.a. [18F]fluorination, Appl. Radiat. Isot. 43:485.

    Article  CAS  Google Scholar 

  • Lemaire, C., Plenevaux, A., Comar, D., 1992b, Feasibility of multimillicurie preparation of L-6-[18F]fluorodopa by nucleophilic asymmetric synthesis, Eur. J. Nucl. Med. 19:591

    Google Scholar 

  • Lemaire, C., 1993a, Production of L-[18F]fluoroamino acids for protein synthesis: overview and recent developments in nucleophilic syntheses, in “PET studies on amino acid metabolism and protein synthesis,” B.M. Mazoyer, W.D. Heiss, D. Comar, ed., Kluwer Academic Publishers, Dordrecht.

    Google Scholar 

  • Lemaire, C., Plenevaux, A., Cantineau, R., Christiaens, L., Guillaume, M., Comar, D., 1993b, Nucleophilic enantioselective synthesis of 6-[18F]fluoro-L-dopa via two chiral auxiliaries, Appl. radiat. Isot. 44:131.

    Article  Google Scholar 

  • Lemaire, C., Plenevaux A., Damhaut, P., Guillaume, M., Christiaens, L., Comar, D., 1993c, NCA asymmetric synthesis of 2-[18F]fluoro-L-tyrosine, J. Labelled Compd. Radiopharm. 32:139.

    Google Scholar 

  • Luxen, A., Perlmutter, M., Bida, G.T., Van Moffaerts, G., Cook, J.S., Satyamurthy, N., Phelps, M.E., Barrio J.R., 1990, Remote, semiautomated production of 6-[18F]fluoro-L-dopa for human studies with PET. Appl. Radiat. Isot. 41:275.

    Article  CAS  Google Scholar 

  • Luxen, A., Guillaume, M., Melega, W.P., Pike V.W., Solin O., Wagner R., 1992, Production of 6-[18F]fluoro-L-dopa and its metabolism In vivo — a critical review, Appl. Radiat. Isot. 19: 149.

    CAS  Google Scholar 

  • Mazière, B., Coenen, H.H., Haldin, C., Nagren, K., Pike, V.W., 1992, PET radioligands for dopamine receptors and re-uptakes sites: chemistry and biochemistry, Nucl. Med. Biol. 19: 497.

    Google Scholar 

  • Mcintosh, J.M., Mishra P., 1986, Alkylation of camphor imines of glycinates. Diastereoselectivity as a function of electronic factors in the alkylating agent. Can. J. Chem. 64: 726.

    Article  CAS  Google Scholar 

  • Murakami, M., Takahashi, K., Kondo, Y., Mizusawa, S., Nakamichi, H., Sasaki, H., Hagami, E., Iida, H., Kanno I., Miura, S., Uemura K., 1988, 2-18F-phenylalanine and 3-18F-tyrosine. Synthesis and preliminary data of tracer kinetics, J. Labelled Compd. Radiopharm. 25: 773.

    Article  CAS  Google Scholar 

  • Namavari, M., Bishop, A., Satyamurthy, N., Bida, G., Barrio, J.R., 1992, Regioselective radiofluorodestannylation with [18F]F2 and [18F]CH3COOF: a high yield synthesis of 6-[18F]fluoro-L-dopa, Appl. Radiat. Isot. 43:989.

    Article  CAS  Google Scholar 

  • Oguri, T., Kawai, N., Shioiri, T., Yamada S., 1978, Amino acids and peptides. XXDC. A new efficient asymmetric synthesis of α-amino acid derivatives with recycle of a chiral reagent- Asymmetric alkylation of a chiral Schiff base from glycine, Chem Pharm Bull 26:803.

    Article  CAS  Google Scholar 

  • Phelps, M.E., Mazziotta, J.C., Scheiben, H.R., “Positron emission tomography and autoradiography, principles and applications for the brain and the heart,” Raven Press, New York (1986).

    Google Scholar 

  • Plenevaux, A., Al-Darwich, M.J., Lemaire, C., Delfiore, G., Christiaens, L., Comar, D., 1993, Asymmetric synthesis of n.c.a. L-[2-11C]-4-chlorophenylalanine, J. Labelled Compd. Radiopharm. 32:156.

    Google Scholar 

  • Reddy, G.N., Haeberli, M., Beer, H.-F., Schubiger, A.P., 1993, An improved synthesis of no-carrier-added (n.c.a.) 6-[18F]fluoro-L-dopa and its remote routine production for PET investigations of dopaminergic systems, Appl. Radiat. isot. 44:645.

    Article  CAS  Google Scholar 

  • Sadzot, B., Lemaire, C., Maquet, M., Plenevaux, A., Salmon, E., Degueldre, C., Hermanne, J.P., Guillaume, M., Cantineau, R., Franck, G., Comar, D., 1993, Serotonin 5HT2 receptor imaging in the human brain using positron emission tomography and a new radioligand, [18F]altanserin. Results in young normal controls. J. Cereb. Blood Flow Metab. (in press).

    Google Scholar 

  • Seebach, D., Dziadulewicz, E., Behrendt, L., Cantoreggi, S., Fitzi, R., 1989, Synthesis of nonproteinogenic (R)- or (S)-amino acids analogues of phenylalanine, isotopically labelled and cyclic amino acids from tert-butyl-2-(tert-butyl)-3-methyl-4-oxo-l-imidazolidinecarboxylate, Liebigs Ann. Chem. 12:1215.

    Article  Google Scholar 

  • Wagner, H.H., Burns, H.D., Dannals, R.F., Wong, D.F., Langstrom, B., Duelfer, T., Frost, J.J., Ravert, H.T., Links, J.M., Rosenbloom, S.B., Lucas, S.E., Kramer, A.V., Kuhar, M.J., 1983, Imaging dopamine receptors in the human brain by positron emission tomography, Science. 221:1264.

    Article  PubMed  CAS  Google Scholar 

  • Williams, M. W., 1989, “Synthesis of optically active α-amino acids,” Pergamon Press, Oxford.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. B-30, Cyclotron Research Center, Liège University, 4000, Liège, Belgium

    Christian Lemaire

Authors
  1. Christian Lemaire
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Health Science Center, The University of Texas, Houston, Texas, USA

    Ali M. Emran

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Springer Science+Business Media New York

About this chapter

Cite this chapter

Lemaire, C. (1995). Fluorine-18 Labeling of Radiopharmaceuticals for PET Studies: Main Aspects and Problems Encountered in Chemical Syntheses. In: Emran, A.M. (eds) Chemists’ Views of Imaging Centers. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9670-4_41

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-9670-4_41

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-9672-8

  • Online ISBN: 978-1-4757-9670-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation