Nuclear Medicine and Biology
Volume 33, Issue 3 , Pages 295-304 , April 2006

Nicotinic α4β2 receptor imaging agents: Part II. Synthesis and biological evaluation of 2-[18F]fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine (18F-nifene) in rodents and imaging by PET in nonhuman primate

Presented in part at the 52nd Annual Society of Nuclear Medicine Meeting, Toronto, Canada, June 18–23, 2005.

  • Rama Pichika

      Affiliations

    • Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960, USA
  • ,
  • Balasubramaniam Easwaramoorthy

      Affiliations

    • Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960, USA
  • ,
  • Daphne Collins

      Affiliations

    • Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960, USA
  • ,
  • Bradley T. Christian

      Affiliations

    • Department of Nuclear Medicine, Kettering Medical Center, Dayton, OH 45429, USA
  • ,
  • Bingzhi Shi

      Affiliations

    • Department of Nuclear Medicine, Kettering Medical Center, Dayton, OH 45429, USA
  • ,
  • Tanjore K. Narayanan

      Affiliations

    • Department of Nuclear Medicine, Kettering Medical Center, Dayton, OH 45429, USA
  • ,
  • Steven G. Potkin

      Affiliations

    • Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960, USA
  • ,
  • Jogeshwar Mukherjee

      Affiliations

    • Brain Imaging Center, Department of Psychiatry and Human Behavior, University of California, Irvine, CA 92697-3960, USA
    • Corresponding Author InformationCorresponding author. Tel.: +1 949 824 2018; fax: +1 949 824 4144.

Received 18 December 2005 ,Revised 21 December 2005 ,Accepted 29 December 2005.

References 

  1. Breese CR, Lee MJ, Adams CE, Sullivan B, Logel J, Gillen KM, et al. Abnormal regulation of high affinity nicotinic receptors in subjects with schizophrenia. Neuropsychopharmacology. 2000;23:351–364
  2. Clementi F, Fornasari D, Gotti C. Neuronal nicotinic acetylcholine receptors: from structure to therapeutics. Trends Pharmacol Sci. 2000;21:35–37
  3. Dani JA. Overview of nicotinic receptors and their roles in the central nervous system. Biol Psychiatry. 2001;49:166–174
  4. Paterson D, Nordberg A. Neuronal nicotinic receptors in the human brain. Prog Neurobiol. 2000;61:75–111
  5. Sacco KA, Bannon KL, George TP. Nicotinic receptor mechanisms and cognition in normal states and neuropsychiatric disorders. J Psychopharmacol. 2004;18:457–474
  6. Sihver W, Nordberg A, Langstrom B, Mukhin AG, Koren AO, Kimes AS, et al. Development of ligands for in vivo imaging of cerebral nicotinic receptors. Behav Brain Res. 2000;113:143–157
  7. Gundisch D, Koren AO, Horti AG, Pavlova OA, Kimes AS, Mukhin AG, et al. In vitro characterization of 6-[18F]fluoro-A-85380, a high-affinity ligand for α4β2 nicotinic acetylcholine receptors. Synapse. 2005;55:89–97
  8. Chattopadhyay S, Xue B, Collins D, Pichika R, Bagnera R, Leslie F, et al. Synthesis and evaluation of nicotine α4β2 receptor radioligand, 5-(3′-18F-fluoropropyl)-3-(2-(S)-pyrrolidinylmethoxy)pyridine, in rodents and PET in nonhuman primate. J Nucl Med. 2005;46:130–140
  9. Kimes AS, Horti AG, London ED, Chefer SI, Contoreggi C, Ernst M, et al. 2-[18F]F-A-85380: PET imaging of brain nicotinic acetylcholine receptors and whole body distribution in humans. FASEB J. 2003;17:1331–1333
  10. Bottlaender M, Valette H, Roumenov D, Dolle F, Coulon C, Ottaviani M, et al. Biodistribution and radiation dosimetry of 18F-fluoro-A-85380 in healthy volunteers. J Nucl Med. 2003;44:596–601
  11. Fujita M, Ichise M, van Dyck CH, Zoghbi SS, Tamagnan G, Mukhin AG, et al. Quantification of nicotinic acetylcholine receptors in human brain using 123I-5-IA85380 SPET. Eur J Nucl Med. 2003;30:1620–1629
  12. Chefer SI, London ED, Koren AO, Pavlova OA, Kurian V, Kimes AS, et al. Graphical analysis of 2-[18F]FA binding to nicotinic acetylcholine receptors in rhesus monkey brain. Synapse. 2003;48:25–34
  13. Abreo MA, Lin N-H, Garvey DS, Gunn DE, Hettinger AM, Wasicak JT, et al. Novel 3-pyridyl ethers with subnanomolar affinity for central neuronal nicotinic acetylcholine receptors. J Med Chem. 1996;39:817–825
  14. Pichika R, Collins D, Christian BT, Shi B, Narayanan TK, Mukherjee J. PET imaging agents for thalamic and extrathalamic α4β2 nicotinic receptors. J Label Compd Radiopharm. 2005;48:S9
  15. Brown L, Chefer S, Pavlova O, Vaupel DB, Koren AO, Kimes AS, et al. Evaluation of 5-(2-(4-pyridinyl)vinyl)-6-chloro-3-(1-methyl-2-(S)-pyrrolidinylmethoxy)pyridine and its analogues as PET radioligands for imaging nicotine acetylcholine receptors. J Neurochem. 2004;91:600–612
  16. Lin N-H, Gunn DE, Li Y, He Y, Bai H, Ryther KB, et al. Synthesis and structure-activity relationships of pyridine-modified analogs of 3-[2-(S)-pyrrolidinyl)pyridine], A-84543. A potent nicotinic acetylcholine receptor agonist. Bioorg Med Chem. 1998;8:249–254
  17. Pabreza LA, Dhawan S, Kellar KJ. [3H]Cytisine binding to nicotinic cholinergic receptors in brain. Mol Pharmacol. 1991;39:9–12
  18. Cheng Y-C, Prusoff WH. Relationship between the inhibition constant and the concentration of inhibitor which cause 50 percent of an enzymatic reaction. Biochem Pharmacol. 1973;22:3099–3108
  19. Smulders CJGM, Zwart R, Bermudez I, van Kleef RGDM, Groot-Kormelink PJ, Vijverberg HPM. Cholinergic drugs potentiate human nicotinic α4β2 acetylcholine receptors by a competitive mechanism. Eur J Pharmacol. 2005;509:97–108
  20. Dolle F, Dolci L, Valette H, Hinnen F, Vaufrey F, Guenther I, et al. Synthesis and nicotinic acetylcholine receptors in vivo binding properties of 2-fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine: a new positron emission tomography ligand for nicotinic receptors. J Med Chem. 1999;42:2251–2259
  21. Hughes DL. In: Organic reactions. vol. 42:New York: John Wiley & Sons, Inc; 1992;p. 335–656
  22. Perry DC, Xiao Y, Nguyen HN, Musachio JL, Davila-Garcia MI, Kellar KJ. Measuring nicotinic receptors with characteristics of α4β2, α3β2 and α3β4 subtypes in rat tissues by autoradiography. J Neurochem. 2002;82:468–481
  23. Ding Y-S, Fowler J, Logan J, Wang GJ, Telang F, Garza V, et al. 6-[18F]Fluoro-A-85380, a new PET tracer for the nicotinic acetylcholine receptor: studies in the human brain and in vivo demonstration of specific binding in the white matter. Synapse. 2004;53:184–189
  24. Horti AG, Koren AO, Ravert HT, Musachio JL, Mathews WB, London ED, et al. Synthesis of a radiotracer for studying nicotinic acetylcholine receptors, 2-[18F]fluoro-3-(2(S)-azetidinylmethoxy) pyridine (2[18F]A-85380). J Label Compd Radiopharm. 1998;35:309–318
  25. Valette H, Bottlaender M, Dolle F, Coulon C, Ottaviani M, Syrota A. Long-lasting occupancy of central nicotinic acetylcholine receptors after smoking: a PET study in monkeys. J Neurochem. 2003;84:105–111
  26. Han ZY, Zoli M, Cardona A, Bourgeois JP, Novere NL. Localization of 3H-nicotine, 3H-cytisine, 3H-epibatidine, and 125I-a-bungaratoxin binding sites in the brain of Macca mulatta. J Comp Neurol. 2003;461:49–60
  27. Perry DC, Davila-Garcia MI, Stockmeier CA, Kellar KJ. Increased nicotinic receptors in brains from smokers: membrane binding and autoradiography studies. J Pharmacol Exp Ther. 1999;289:1545–1552
  28. Schmaljohann J, Minnerop M, Karwath P, Gundisch D, Falkai P, Guhlke S, et al. Imaging of central nAChR receptors with 2-18F-A85380: optimized synthesis and in vitro evaluation in Alzheimer's disease. Appl Radiat Isot. 2004;61:1235–1240

PII: S0969-8051(06)00003-5

doi: 10.1016/j.nucmedbio.2005.12.017

Nuclear Medicine and Biology
Volume 33, Issue 3 , Pages 295-304 , April 2006