Skip to main content
SpringerLink
Log in

The Development of Radiopharmaceuticals for Imaging CNS Receptors

  • Chapter
Current Directions in Radiopharmaceutical Research and Development

Part of the book series: Developments in Nuclear Medicine ((DNUM,volume 30))

Abstract

Receptors are special protein molecules that recognize or selectively bind to drugs, hormones or neurotransmitters (see figure 1). There are various types of receptors, including hormone, peptide, biogenic amine and ion channel. Ligands are chemical molecules that fit the receptor binding sites. The extent of ligand-receptor interaction is usually expressed in terms of binding affinity; it represents the binding constant at equilibrium (Kd, dissociation constant; or Ki, inhibition constant). When a ligand is bound to a receptor (R) located in the cell membrane, the ligand-receptor complex triggers responses of secondary messengers (i.e., induce protein kinase activity). There is a large number of CNS receptors responsible for different types of neuronal function.

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 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
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

  1. Strange PG. Multiple dopamine receptors: relevance for neurodegenerative disorders [review]. Biochem Soc Trans 22(1): 155–159, 1994.

    PubMed  CAS  Google Scholar 

  2. Waddington JL, O’Boyle KM. Drugs acting on brain dopamine receptors: a conceptual re-evaluation five years after the first selective D1 antagonist. Pharmacol Ther 43:1, 1989.

    Article  PubMed  CAS  Google Scholar 

  3. Sibley DR, Monsma FJ, Jr., Shen Y. Molecular neurobiology of dopaminergic receptors. Int Rev Neurobiol 35:391–415, 1993.

    Article  PubMed  CAS  Google Scholar 

  4. Strange PG. New insights into dopamine receptors in the central nervous system. Neurochem Int 22(3):223–236, 1993.

    Article  PubMed  CAS  Google Scholar 

  5. Vanleeuwen DH, Eisenstein J, O’Malley K, Mackenzie RG. Characterization of a chimeric human dopamine D3/D2 receptor functionally coupled to adenylyl-cyclase in Chinese hamster ovary cells. Mol Pharmacol 48(2):344–351, 1995.

    CAS  Google Scholar 

  6. Eckelman WC. The status of radiopharmaceutical research. Nucl Med Biol — Int J Rad Appl Inst Part B 18(7):iii-vi, 1991.

    CAS  Google Scholar 

  7. Fowler JS, Wolf AP. Recent advances in radiotracers for PET studies of the brain. Ann Rep Med Chem, 1990.

    Google Scholar 

  8. Matsuda H, Li YM, Higashi S, Sumiya H, Tsuji S, Kinuya K, Hisada K, Yamashita J. Comparative SPECT study of stroke using Tc-99m ECD, 1–123 IMP, and Tc-99m HMPAO. Clin Nucl Med 18(9):754–758, 1993.

    Article  PubMed  CAS  Google Scholar 

  9. Léveillé J, Demonceau G, Walovitch RC. Intrasubject comparison between technetium-99m-ECD and technetium-99m-HMPAO in healthy human subjects. J Nucl Med 33(4):480–484, 1992.

    PubMed  Google Scholar 

  10. Jurisson SS, Berning D, Jia W, Ma D-S. Coordination compounds in nuclear medicine. Chem Rev 93(3): 1137–1156, 1993.

    Article  CAS  Google Scholar 

  11. Steigman J, Eckelman WC. The Chemistry of Technetium in Medicine. Washington, DC: National Academy Press, 1992.

    Google Scholar 

  12. Farde L. Selective D1 and D2 dopamine receptor blockade both induces akathisia in humans--a PET study with [11C]SCH23390 and [11C]raclopride. Psychopharmacology (Berl) 107(1):23–29, 1992.

    Article  CAS  Google Scholar 

  13. Farde L, Wiesel FA, Stone-Elander S, Halldin C, Nordström AL, Hall H, Sedvall G. D2 dopamine receptors in neuroleptic-naive schizophrenic patients. A positron emission tomography study with [11C] raclopride. Arch Gen Psychiatry 47(3):213–219, 1990.

    PubMed  CAS  Google Scholar 

  14. Volkow ND, Fowler JS, Wang GJ, et al. Reproducibility of repeated measures of carbon-11-raclopride binding in the human brain. J Nucl Med 34:609–613, 1993.

    PubMed  CAS  Google Scholar 

  15. Wong DF. PET studies of neuroreceptors in schizophrenia. Commentary on “The current status of PET scanning with respect to schizophrenia.” Neuropsychopharmacology 7(1):69–72, 1992.

    PubMed  CAS  Google Scholar 

  16. Sedvall G. The current status of PET scanning with respect to schizophrenia. Neuropsychopharmacology 7(1):41–54, 1992.

    PubMed  CAS  Google Scholar 

  17. Seeman P, Guan H-C, Niznik HB. Endogenous dopamine lowers the dopamine D2 receptor density as measured by [3H]raclopride: implications for positron emission tomography of the human brain. Synapse 3(96–97), 1989.

    Article  PubMed  CAS  Google Scholar 

  18. Young LT, Wong DF, Goldman S, Minkin E, Chen C, Matsumura K, Scheffel U, Wagner HN, Jr. Effects of endogenous dopamine on kinetics of [3H]N-methylspiperone and [3H]raclopride binding in the rat brain. Synapse 9(3):188–194, 1991.

    Article  PubMed  CAS  Google Scholar 

  19. Andreasen NC, Carson R, Diksic M, Evans A, Farde L, Gjedde A, Hakim A, Lal S, Nair N, Sedvall G, Tune L, Wong D. Workshop on schizophrenia, PET, and dopamine D2 receptors in the human neostriatum. Schizophr Bull 14(3):471–484, 1988.

    PubMed  CAS  Google Scholar 

  20. Kung HF, Kasliwal R, Pan S, Kung M-P, Mach RH, Guo Y-Z. Dopamine D2 receptor imaging radiopharmaceuticals: synthesis, radiolabeling and in vitro binding of (R)-(+)- and (S)-(-)-3-iodo-2-hydroxy-6-memoxy-N-[(1-ethyl-2-pynolidinyl)-methyl]-benzamide. J Med Chem 31(5): 1039–1043, 1988.

    Article  PubMed  CAS  Google Scholar 

  21. Kung HF, Alavi A, Chang W, Kung M-P, Keyes JW, Jr., Velchik MG, Billings J J, Pan S, Noto R, Rausch A, Reilley J. In vivo SPECT imaging of CNS D2 dopamine receptors: initial studies with iodine-123-IBZM in humans. J Nucl Med 31:573–579, 1990a.

    CAS  Google Scholar 

  22. Brücke T, Wenger S, Asenbaum S, Fertl E, Pfafflmeyer N, Müller C, Podreka I, Angelberger P. Dopamine D2 receptor imaging and measurement with SPECT. Adv Neurol 60:494–500, 1993.

    PubMed  Google Scholar 

  23. Ichise M, Toyama H, Fonazzari I, Ballinger JR, Kirsch JC. Assessment of subjects with and at risk for developing Huntington’s disease by I-123 IBZM and Tc-99m HM-PAO SPECT [abstract]. J Nucl Med 33:970, 1992.

    Google Scholar 

  24. Knable MB, Jones DW, Coppola R, Hyde TM, Lee KS, Gorey J, Weinberger DR. Lateralized differences in iodine-123-IBZM uptake in the basal ganglia in asymmetric Parkinson’s disease. J Nucl Med 36(7): 1216–1225, 1995.

    PubMed  CAS  Google Scholar 

  25. Laruelle MA, Abi-Dargham A, van Dyck CH, Rosenblatt W, Zea-Ponce Y, Zoghbi SS, Baldwin RM, Charney DS, Hoffer PB, Kung HF, Innis RB. SPECT imaging of striatal dopamine release after amphetamine challenge. J Nucl Med 36(7): 1182–1190, 1995.

    PubMed  CAS  Google Scholar 

  26. Schlosser R, Schlegel S. D2 receptor imaging with [123I]IBZM and single photon emission tomography in psychiatry: a survey of current status. J Neural Transm — Gen Sect 99(1): 173–185, 1995.

    Article  PubMed  CAS  Google Scholar 

  27. Schwarz J, Tatsch K, Arnold G, Gasser T, Trenkwalder C, Kirsch CM, Oertel WH. [123I]. iodobenzamide-SPECT predicts dopaminergic responsiveness in patients with de novo Parkinsonism. Neurology, 1992.

    Google Scholar 

  28. Scibyl J, Woods S, Zoghbi SS, Baldwin RM, Dey HM, Goddard AW, Zea-Ponce Y, Zubal G, Germine M, Smith EO, Heninger GR, Charney DS, Kung HF, Alavi A, Hoffer PB, Innis RB. Dynamic SPECT imaging of dopamine D2 receptors in human subjects with iodine-123-IBZM. J Nucl Med 33:1964–1971, 1992.

    Google Scholar 

  29. Tatsch K, Schwartz J, Oertel WH, Kirsh CM. Dopamine D2 receptor imaging with [123I]IBZM SPECT to differentiate idiopathic from other Parkinson syndromes [abstract]. J Nucl Med 33:917–918, 1992.

    Google Scholar 

  30. Carroll FI, Lewin AH, Boja JW, Kuhar MJ. Cocaine receptor: biochemical characterization and structure-activity relationships of cocaine analogues at the dopamine transporter. J Med Chem 35(6):969–981, 1992.

    Article  PubMed  CAS  Google Scholar 

  31. Carroll FI, Mascarella SW, Kuzemko MA, Gao Y, Abraham P, Lewin AH, Boja JW, Kuhar MJ. Synthesis, ligand binding, and QSAR (CoMFA and classical) study of 3b-(3′-substituted phenyl)-, 3b-(4′-substituted phenyl)-, and 3b-(3′,4′-disubstituted phenyl)tropane-2b-carboxylic acid methyl esters. J Med Chem 37:2865–2873, 1994.

    Article  PubMed  CAS  Google Scholar 

  32. Fowler JS, Volkow ND, Wolf AP, Dewey SL, Schlyer DJ, Macgregor RR, Hitzemann R, Logan J, Bendriem B, Gatley S J. Mapping cocaine binding sites in human and baboon brain in vivo. Synapse 4(4):371–377, 1989.

    Article  PubMed  CAS  Google Scholar 

  33. Fowler JS, Volkow ND, MacGregor RR, Logan J, Dewey SL, Gatley SJ, Wolf AP. Comparative PET studies of the kinetics and distribution of cocaine and cocaethylene in baboon brain. Synapse 12(3):220–227, 1992.

    Article  PubMed  CAS  Google Scholar 

  34. Frost JJ, Rosier AJ, Reich SG, Smith JS, Ehlers MD, Snyder SH, Ravert HT, Dannais RF. Positron emission tomographic imaging of the dopamine transporter with [11C]-WIN 35,428 reveals marked declines in mild Parkinson’s disease. Ann Neurol 34(3):423–431, 1993.

    Article  PubMed  CAS  Google Scholar 

  35. Innis RB. Single photon emission tomography imaging of dopamine terminal innervation: a potential clinical tool in Parkinson’s disease [editorial; review]. Eur J Nucl Med 21(1): 1–5, 1994.

    Article  PubMed  CAS  Google Scholar 

  36. Wong DF, Yung B, Dannals RF, Shaya EK, Ravert HT, Chen CA, Chan B, Folio T, Scheffel U, Ricaurte GA, et al. In vivo imaging of baboon and human dopamine transporters by positron emission tomography using [11C]WIN35,428. Synapse 15:130–142, 1993.

    Article  PubMed  CAS  Google Scholar 

  37. Goodman MM, Kung M-P, Kabalka GW, Kung HF, Switzer R. Synthesis and characterization of radioiodinated N-(3-iodopropen-1-yl)-2b-carbomethoxy-3b-(4-chlorophenyl)tropanes: potential dopamine reuptake site imaging agents. J Med Chem 37:1535–1542, 1994.

    Article  PubMed  CAS  Google Scholar 

  38. Kung M-P, Essman WD, Frederick D, Meegalla SK, Goodman MM, Mu M, Lucki I, Kung HF. IPT: a novel iodinated ligand for the CNS dopamine transporter. Synapse 20(4):316–324, 1995.

    Article  PubMed  CAS  Google Scholar 

  39. Mozley PD, Stubbs JB, Kim H-J, McElgin WT, Kung M-P, Meegalla SK, Kung HF. Dosimetry of an iodine-123-labeled tropane to image dopamine transporters. J Nucl Med 37(1): 151–159, 1996.

    PubMed  CAS  Google Scholar 

  40. Malison RT, Vessotskie JM, Kung M-P, McElgin WT, Romaniello G, Kim H-J, Goodman MM, Kung HF. Striatal dopamine transporter imaging in non-human primates with iodine-123-IPT SPECT. J Nucl Med 36(12):2290–2297, 1995.

    PubMed  CAS  Google Scholar 

  41. Neumeyer JL, Wang S, Gao Y, Milius RA, Kula NS, Campbell A, Baldessarini RJ, Zea-Ponce Y, Baldwin RM, Innis RB. N-w-Fluoroalkyl analogs of (1R)-2b-carbomethoxy-3b-(4-iodophenyl)-tropane (b-CIT): radiotracers for positron emission tomography and single photon emission computed tomography imaging of dopamine transporters. J Med Chem 37(11): 1558–1561, 1994.

    Article  PubMed  CAS  Google Scholar 

  42. Lever SZ, Baidoo KE, Mahmood A, Matsumura K, Scheffel UA, Wagner HN, Jr. Novel technetium ligands with affinity for the muscarinic cholinergic receptor. Nucl Med Biol 21(2): 157–164, 1994.

    Article  PubMed  CAS  Google Scholar 

  43. Tatsch, K. Unpublished results.

    Google Scholar 

  44. Del Rosario RB, Jung Y-W, Baidoo KE, Lever SZ, Wieland DM. Synthesis and in vivo evaluation of a [99m/99Tc]-DADT-benzovesamicol: a potential marker for cholinergic neurons. Nucl Med Biol 21(2): 197–203, 1994.

    Article  PubMed  Google Scholar 

  45. Chi DY, Katzenellenbogen JA. Selective formation of heterodimeric bis-bidentate aminothiol-oxometal complexes of rhenium(V). J Am Chem Soc 115(15):7045–7046, 1993.

    Article  CAS  Google Scholar 

  46. Chi DY, O’Neil JP, Anderson CJ, Welch MJ, Katzenellenbogen JA. Homodimeric and heterodimeric bis(amino thiol) oxometal complexes with rhenium(V) and technetium(V): control of heterodimeric complex formation and an approach to metal complexes that mimic steroid hormones. J Med Chem 37(7):928–937, 1994.

    Article  PubMed  CAS  Google Scholar 

  47. DiZio JP, Anderson CJ, Davison A, Ehrhardt GJ, Carlson KE, Welch MJ, Katzenellenbogen JA. Technetium- and rhenium-labeled progestins: synthesis, receptor binding and in vivo distribution of an 11 beta-substituted progestin labeled with technetium-99 and rhenium-186. J Nucl Med 33(4):558–569, 1992.

    PubMed  CAS  Google Scholar 

  48. DiZio JP, Fiaschi R, Davison A, Jones AG, Katzenellenbogen JA. Progestin-rhenium complexes: metal-labeled steroids with high receptor binding affinity, potential receptor-directed agents for diagnostic imaging or therapy. Bioconj Chem 2(5):353–366, 1991.

    Article  CAS  Google Scholar 

  49. O’Neil JP, Carlson KE, Anderson CJ, Welch MJ, Katzenellenbogen JA. Progestin radiopharmaceuticals labeled with technetium and rhenium: synthesis, binding affinity, and in vivo distribution of a new progestin N2S2-metal conjugate. Bioconj Chem 5(3): 182–193, 1994a.

    Article  Google Scholar 

  50. O’Neil JP, Wilson SR, Katzenellenbogen JA. Preparation and structural characterization of monoamine-monoamide bis(thiol) oxo complexes of technetium(V) and rhenium(V). Inorg Chem 33(2):319–323, 1994b.

    Article  Google Scholar 

  51. Jurisson SS, Pirro J, DiRocco RJ, Rosenspire KC, Jagoda E, Nanjappan P, Eckelman WC, Nowotnik DP, Nunn AD. Boronic acid adducts of technetium dioxime (BATO) complexes derived from quinuclidine benzilate (QNB) boronic acid stereoisomers: syntheses and studies of their binding to the muscarinic acetylcholine receptor. Nucl Med Biol 22(3):269–281, 1995.

    Article  PubMed  CAS  Google Scholar 

  52. Kung HF. New technetium 99m-labeled brain perfusion imaging agents. Semin Nucl Med 20(2): 150–158, 1990.

    Article  PubMed  CAS  Google Scholar 

  53. Kung HF, Liu B-L, Francesconi LC, Ohmomo Y, Billings JJ, Kung M-P. Metal N2S2 complexes in radiopharmaceutical development. J Lab Compds Radiopharm 30:29–30, 1990b.

    Google Scholar 

  54. Meegalla, SK. Unpublished results.

    Google Scholar 

  55. Mastrostamatis SG, Papadopoulos MS, Pirmettis IC, Paschali E, Varvarigou AD, Stassinopoulou CI, Raptopoulou CP, Terzis A, Chiotellis E. Tridentate ligands containing the SNS donor atom set as a novel backbone for the development of technetium brain imaging agents. J Med Chem 37(20):3212–3218, 1994.

    Article  PubMed  CAS  Google Scholar 

  56. Spies H, Fietz T, Glaser M, Pietzsch H-J, Johannsen B. The “n+1” concept in the synthesis strategy of novel technetium and rhenium tracers. In Technetium and Rhenium in Chemistry and Nuclear Medicine, Volume 4. Nicolini M, Bandoli G, Mazzi U. Padova, Italy: S. G. Editoriali:243–246, 1995.

    Google Scholar 

  57. Spies H, Pietzsch H-J, Hahn FE, Kintzel O, Lügger T. Trigonal-bipyramidal technetium and rhenium complexes with tetradentate NS3 tripod ligands. Angew Chem Int Ed Engl 33:1354–1356, 1994.

    Article  Google Scholar 

  58. Meegalla SK, Plössl K, Kung M-P, Stevenson DA, Liable-Sands LM, Rheingold AL, Kung HF. The first example of a Tc-99m complex as a dopamine transporter imaging agent. J Am Chem Soc 117(44): 11037–11038, 1995.

    Article  CAS  Google Scholar 

Download references

Authors
  1. Hank F. Kung
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Nuclear Medicine, Imperial Cancer Research Fund, St. Bartholomew’s Hospital, London, EC1A 7BE, UK

    Stephen J. Mather

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Kluwer Academic Publishers

About this chapter

Cite this chapter

Kung, H.F. (1996). The Development of Radiopharmaceuticals for Imaging CNS Receptors. In: Mather, S.J. (eds) Current Directions in Radiopharmaceutical Research and Development. Developments in Nuclear Medicine, vol 30. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-1768-2_7

Download citation

  • DOI: https://doi.org/10.1007/978-94-009-1768-2_7

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-7289-2

  • Online ISBN: 978-94-009-1768-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation