Nuclear Medicine and Biology
Volume 37, Issue 1 , Pages 35-40 , January 2010

Radiosynthesis and ex vivo evaluation of (R)-(−)-2-chloro-N-[1-11C-propyl]n-propylnorapomorphine

  • Mikael Palner

      Affiliations

    • Neurobiology Research Unit, Rigshospitalet, University of Copenhagen, DK-2300, Copenhagen, Denmark
    • Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark
    • Corresponding Author InformationCorresponding author. Neurobiology Research Unit, Rigshospitalet, DK-2100 Copenhagen, Denmark. Tel.: +45 3545 6704; fax: +45 3545 6713.
  • ,
  • Patrick McCormick

      Affiliations

    • PET Centre, Centre for Addiction and Mental Health, M5T 1RB, Toronto, ON, Canada
  • ,
  • Nic Gillings

      Affiliations

    • Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark
    • PET and Cyclotron Unit, Rigshospitalet, DK-2300, Copenhagen, Denmark
  • ,
  • Mikael Begtrup

      Affiliations

    • Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark
    • Institute for Medicinal Chemistry, Pharmaceutical Faculty, University of Copenhagen, DK-2300, Copenhagen, Denmark
  • ,
  • Alan A. Wilson

      Affiliations

    • PET Centre, Centre for Addiction and Mental Health, M5T 1RB, Toronto, ON, Canada
  • ,
  • Gitte M. Knudsen

      Affiliations

    • Neurobiology Research Unit, Rigshospitalet, University of Copenhagen, DK-2300, Copenhagen, Denmark
    • Center for Integrated Molecular Brain Imaging, Copenhagen, Denmark

Received 13 March 2009 ,Revised 4 August 2009 ,Accepted 23 August 2009.

References 

  1. Seeman P, Schwarz J, Chen JF, Szechtman H, Perreault M, McKnight GS, et al. Psychosis pathways converge via D2 high dopamine receptors. Synapse. 2006;60(4):319–346
  2. Dentresangle C, Veyre L, Le BD, Pierre C, Lavenne F, Pollak P, et al. Striatal D2 dopamine receptor status in Parkinson's disease: an [18F]dopa and [11C]raclopride PET study. Mov Disord. 1999;14(6):1025–1030
  3. Toda M, bi-Dargham A. Dopamine hypothesis of schizophrenia: making sense of it all. Curr Psychiatry Rep. 2007;9(4):329–336
  4. Stoof JC, Kebabian JW. Two dopamine receptors: biochemistry, physiology and pharmacology. Life Sci. 1984;35(23):2281–2296
  5. Sibley DR, De LA, Creese I. Anterior pituitary dopamine receptors. Demonstration of interconvertible high and low affinity states of the D-2 dopamine receptor. J Biol Chem. 1982;257(11):6351–6361
  6. Seeman P, Tallerico T, Ko F. Dopamine displaces [3H]domperidone from high-affinity sites of the dopamine D2 receptor, but not [3H]raclopride or [3H]spiperone in isotonic medium: implications for human positron emission tomography. Synapse. 2003;49(4):209–215
  7. Kortekaas R, Maguire RP, Cremers TI, Dijkstra D, Van WA, Leenders KL. In vivo binding behavior of dopamine receptor agonist (+)-PD 128907 and implications for the “ceiling effect” in endogenous competition studies with [(11)C]raclopride—a positron emission tomography study in Macaca mulatta. J Cereb Blood Flow Metab. 2004;24(5):531–535
  8. McCormick PN, Kapur S, Seeman P, Wilson AA. Dopamine D2 receptor radiotracer [11C](+)-PHNO and [3H]raclopride are indistinguishably inhibited by D2 agonists and antagonists ex vivo. Nucl Med Biol. 2008;35(1):11–17
  9. Cumming P, Wong DF, Gillings N, Hilton J, Scheffel U, Gjedde A. Specific binding of [(11)C]raclopride and N-[(3)H]propyl-norapomorphine to dopamine receptors in living mouse striatum: occupancy by endogenous dopamine and guanosine triphosphate-free G protein. J Cereb Blood Flow Metab. 2002;22(5):596–604
  10. Narendran R, Hwang DR, Slifstein M, Talbot PS, Erritzoe D, Huang Y, et al. In vivo vulnerability to competition by endogenous dopamine: comparison of the D2 receptor agonist radiotracer (−)-N-[11C]propyl-norapomorphine ([11C]NPA) with the D2 receptor antagonist radiotracer [11C]-raclopride. Synapse. 2004;52(3):188–208
  11. Seneca N, Finnema SJ, Farde L, Gulyas B, Wikstrom HV, Halldin C, et al. Effect of amphetamine on dopamine D2 receptor binding in nonhuman primate brain: a comparison of the agonist radioligand [11C]MNPA and antagonist [11C]raclopride. Synapse. 2006;59(5):260–269
  12. Hwang DR, Kegeles LS, Laruelle M. (−)-N-[(11)C]Propyl-norapomorphine: a positron-labeled dopamine agonist for PET imaging of D(2) receptors. Nucl Med Biol. 2000;27(6):533–539
  13. Finnema SJ, Seneca N, Farde L, Shchukin E, Sovago J, Gulyas B, et al. A preliminary PET evaluation of the new dopamine D2 receptor agonist [11C]MNPA in cynomolgus monkey. Nucl Med Biol. 2005;32(4):353–360
  14. Wilson AA, McCormick P, Kapur S, Willeit M, Garcia A, Hussey D, et al. Radiosynthesis and evaluation of [11C]-(+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol as a potential radiotracer for in vivo imaging of the dopamine D2 high-affinity state with positron emission tomography. J Med Chem. 2005;48(12):4153–4160
  15. Shi B, Narayanan TK, Christian BT, Chattopadhyay S, Mukherjee J. Synthesis and biological evaluation of the binding of dopamine D2/D3 receptor agonist, (R,S)-5-hydroxy-2-(N-propyl-N-(5′-(18)F-fluoropentyl)aminotetralin ((18)F-5-OH-FPPAT) in rodents and nonhuman primates. Nucl Med Biol. 2004;31(3):303–311
  16. Narendran R, Slifstein M, Guillin O, Hwang Y, Hwang DR, Scher E, et al. Dopamine (D2/3) receptor agonist positron emission tomography radiotracer [11C]-(+)-PHNO is a D3 receptor preferring agonist in vivo. Synapse. 2006;60(7):485–495
  17. Ramsby S, Neumeyer JL, Grigoriadis D, Seeman P. 2-Haloaporphines as potent dopamine agonists. J Med Chem. 1989;32(6):1198–1201
  18. Sondergaard K, Kristensen JL, Palner M, Gillings N, Knudsen GM, Roth BL, et al. Synthesis and binding studies of 2-arylapomorphines. Org Biomol Chem. 2005;3(22):4077–4081
  19. Hilton J, Yokoi F, Dannals RF, Ravert HT, Szabo Z, Wong DF. Column-switching HPLC for the analysis of plasma in PET imaging studies. Nucl Med Biol. 2000;27(6):627–630
  20. Freedman SB, Patel S, Marwood R, Emms F, Seabrook GR, Knowles MR, et al. Expression and pharmacological characterization of the human D3 dopamine receptor. J Pharmacol Exp Ther. 1994;268(1):417–426
  21. Palner M, Syvanen S, Kristoffersen US, Gillings N, Kjaer A, Knudsen GM. The Effect of a P-glycoprotein inhibitor on rat brain uptake and binding of [18F]altanserin; a micro-PET study. J Cereb Blood Flow Metab. 2007;27(Suppl 1):

 This work was supported by the Danish Agency for Science, Technology and Innovation; Rigshospitalet; the EC-FP6-project DiMI, LSHB-CT-2005-512146; the Centre of Addiction and Mental Health in Toronto, Canada; and the Lundbeck Foundation, Denmark. Ki determinations were generously performed by the National Institute of Mental Health's Psychoactive Drug Screening Program (NIMH PDSP), contract no. NO1MH32004.

PII: S0969-8051(09)00216-9

doi: 10.1016/j.nucmedbio.2009.08.005

Nuclear Medicine and Biology
Volume 37, Issue 1 , Pages 35-40 , January 2010