Radioligands for Central Neuroreceptors

  • Marleen Vandecapelle
  • Guido Slegers
  • Filip De Vos
  • Filip Dumont


In the development of a new radioligand for a (sub)type of a central neuroreceptor, the selection of the ligand is of crucial importance. It should possess high affinity and selectivity for the concerned receptor type and be able to enter the brain without giving high nonspecific binding. Metabolism of the ligand is preferably slow or results in labelled metabolites that are unable to enter the brain. The incorporated radioisotope should have a physical half-life compatible with the imaging study done and its radiation should be of the correct type and energy to be detected by the external imaging system. Before entering the final developmental stage of in vivo evaluation in animals and human volunteers, a number of (radio)pharmaceutical quality control criteria should be drawn up for the new potential radioligand.


High Performance Liquid Chromatography Single Photon Emission Compute Tomography European Pharmacopoeia Radionuclidic Purity Positron Emission Tomography Camera 
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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  1. Andrée B, Halldin C, Pike VW, Gunn RN, Olsson H, Farde L (2002) The PET Radioligand [carbonyl-11C]desmethyl-WAY-100635 binds to 5-HT1A receptors and provides a higher radioactive signal than [carbonyl-11C]WAY-100635 in the human brain. J Nucl Med 43:292–303PubMedGoogle Scholar
  2. Bergström KA, Meixiang Y, Kuikka JT, Âkerman KK, Hiltunen J, Lehtonen J, Halldin C, Tiihonen J (2000) Metabolism of [123I]epidepride may affect brain dopamine D2 receptor imaging with single-photon emission tomography. Eur J Nucl Med 27:206–208PubMedCrossRefGoogle Scholar
  3. Cheng Y, Prusoff WH (1973) Relationship between the inhibition constant (Ki) and the concentration of inhibitor which causes 50 per cent inhibition (IC50) of an enzymatic reaction. Biochem Pharmacol 22:3099PubMedCrossRefGoogle Scholar
  4. Cliffe IA (2000) A retrospect on the discovery of WAY-100635 and the prospect for improved 5-HT1A receptor PET radioligand. Nucl Med Biol 27:441–447PubMedCrossRefGoogle Scholar
  5. Dichino DD, Welch MJ, Kilbourn MR, Raichle ME (1983) Relationship between lipophilicity and brain extraction of C-11 labeled radiopharmaceuticals. J Nucl Med 24:1030–1038Google Scholar
  6. Eisinga PH (2002) Radiopharmaceutical chemistry for positron emission tomography. Methods 27:208–217CrossRefGoogle Scholar
  7. European Pharmacopoeia (1997) Radiopharmaceutical preparations 1997:0125, pp 1424–1433Google Scholar
  8. Forster EA, Cliffe IA, Bill DJ, Dover GM, Jones D, Reilly Y, Fletcher A (1995) A pharmacological profile of the selective silent 5-HT1A receptor antagonist, WAY-100635. Eur J Pharmacol 281: 81–88PubMedCrossRefGoogle Scholar
  9. Gozlan H, Thibault S, Laporte A, Lima L, Hamon M (1995) The selective 5-HT1A antagonist radioligand [3H] WAY 100635 labels both G-protein-coupled and free 5-HT1A receptors in rat brain membranes. Eur J Pharmacol Mol Pharmacol Sect 288:173–186CrossRefGoogle Scholar
  10. Houle S, DaSilva JN, Wilson AA (2000) Imaging the 5-HT1A receptors with PET: WAY-100635 and analogues. Nucl Med Biol 27:463–466PubMedCrossRefGoogle Scholar
  11. Kuikka JT, Bergström KA, Vanninen E, Laulumaa V, Hartikainen P, Länsimies E (1993) Initial experience with SPET examinations using [123I]2α-carbomethoxy-3α-(4-iodophenyl)tropane ([123I]â-CIT) in human brain. Eur J Nucl Med 20:783–786PubMedCrossRefGoogle Scholar
  12. Meyer GJ, Coenen HH, Waters SL, Langström B, Cantineau R, Strijckmans K, Vaalburg W, Halldin C, Crouzel C, Mazière B, Luxen A (1993) Quality assurance and quality control of short-lived radiopharmaceuticals for PET. In: Stöcklin G, Pike VW (eds) Radiopharmaceuticals for positron tomography — methodological aspects. Kluwer Academic, Dordrecht, pp 91–147CrossRefGoogle Scholar
  13. Müller L, Halldin C, Farde L (1993) [nC]â-CIT, a cocaine analogue, preparation, autoradiography and preliminary PET investigations. Nucl Med Biol 20:249–255PubMedCrossRefGoogle Scholar
  14. Pardridge WM (1991) Peptide drug delivery to the brain. Raven, New YorkGoogle Scholar
  15. Passchier J, Van Waarde A (2001) Visualisation of serotonin-1A (5-HT1A) receptors in the central nervous system. Eur J Nucl Med 28:113–129PubMedCrossRefGoogle Scholar
  16. Passchier J, Gee A, Willemsen A, Vaalburg W, Van Waarde A (2002) Measuring drug-related receptor occupancy with positron emission tomography. Methods 27:278–286PubMedCrossRefGoogle Scholar
  17. Rosenthal HE (1967) Graphical method for the determination and presentation of binding parameters in a complex system. Anal Biochem 20:525–532PubMedCrossRefGoogle Scholar
  18. Suzuki H, Terasaki T, Sugiyama Y (1997) Role of efflux transport across the blood-brain barrier and blood cerebrospinal fluid barrier on the disposition of xenobiotics in the central nervous system. Adv Drug Deliv Rev 25:257–285CrossRefGoogle Scholar
  19. Tamai I, Tsuji A (1996) Drug delivery through the blood brain barrier. Adv Drug Deliv Rev 19: 401–424CrossRefGoogle Scholar
  20. Wade LA, Katzman R (1975) Rat brain regional uptake and decarboxylation of L-DOPA following carotid injection. Am J Physiol 228:352–359PubMedGoogle Scholar
  21. Waterhouse RN, Mardon K, Giles KM, Collier TL, O’Brien JC (1997) Halogenated 4-(phenoxy methyl)piperidines as potential radiolabelled probes for sigma-1 receptors: in vivo evaluation of [123I]-l-(iodopropen-2-yl)-4-[(4-cyanophenoxy)methyl]piperidine. J Med Chem 40: 1657–1667PubMedCrossRefGoogle Scholar
  22. Wilson AA, Jin L, Garcia A, DaSilva JN, Houle S (2001) An admonition when measuring the lipophilicity of radiotracers using counting techniques. Appl Radiat Isotopes 54:203–208CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2004

Authors and Affiliations

  • Marleen Vandecapelle
    • 1
  • Guido Slegers
    • 1
  • Filip De Vos
    • 1
  • Filip Dumont
    • 1
  1. 1.Laboratory for Radiopharmacy, Faculty of Pharmaceutical SciencesGhent UniversityGentBelgium

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