Nuclear Medicine and Biology
Volume 33, Issue 5 , Pages 593-597 , July 2006

Synthesis, radiolabeling and in vivo evaluation of [11C]RAL-01, a potential phosphodiesterase 5 radioligand

  • Steen Jakobsen

      Affiliations

    • PET Centre, Aarhus University Hospitals, 8000 Aarhus, Denmark
    • Corresponding Author InformationCorresponding author.
    • ,
  • Gitte Munkebo Kodahl

      Affiliations

    • PET Centre, Aarhus University Hospitals, 8000 Aarhus, Denmark
    • ,
  • Aage Kristian Olsen

      Affiliations

    • PET Centre, Aarhus University Hospitals, 8000 Aarhus, Denmark
    • ,
  • Paul Cumming

      Affiliations

    • PET Centre, Aarhus University Hospitals, 8000 Aarhus, Denmark
    • Centre for Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark

Received 23 November 2005 ,Revised 11 April 2006 ,Accepted 30 April 2006.

References 

  1. Halldin C, Gulyas B, Farde L. PET studies with carbon-11 radioligands in neuropsychopharmacological drug development. Curr Pharm Des. 2001;7:1907–1929
  2. Marthi K, Hansen SB, Jakobsen S, Bender D, Smith SB, Smith DF. Biodistribution and radiation dosimetry of [N-methyl-11C]mirtazapine, an antidepressant affecting adrenoceptors. Appl Radiat Isot. 2003;59:175–179
  3. Bengel FM, Schwaiger M. Assessment of cardiac sympathetic neuronal function using PET imaging. J Nucl Cardiol. 2004;11:603–616
  4. Muller A, Koch B, Réne F, Boutillier AL, See V, Loeffler JP. Mécanismes de la tolérance et de la dépendance aux opioïdes. Ann Fr Anesth Réanim. 1999;18:866–895
  5. Lourenco CM, Houle S, Wilson AA, DaSilva JN. Characterization of R-[(11)C]rolipram for PET imaging of phosphodieterase-4: in vivo binding, metabolism, and dosimetry studies in rats. Nucl Med Biol. 2001;28:347–358
  6. Parker CA, Matthews JC, Gunn RN, Martarello L, Cunningham VJ, Dommett D, et al. Behaviour of [11C]R(−)- and [11C]S(+)-rolipram in vitro and in vivo, and their use as PET radiotracers for the quantificative assay of PDE4. Synapse. 2005;55:270–279
  7. Ye Y, O'Donnell JM. Diminished noradrenergic stimulation reduces the activity of rolipram-sensitive, high-affinity cyclic AMP phosphodiesterase in rat cerebral cortex. J Neurochem. 1996;66:1894–1902
  8. Zhao Y, Zhang HT, O'Donnell JM. Antidepressant-induced increase in high-affinity rolipram binding sites in rat brain: dependence on noradrenergic and serotonergic function. J Pharmacol Exp Ther. 2003;307:246–253
  9. Poulsen PH, Smith DF, Østergaard L, Danielsen EH, Gee A, Hansen SB, et al. In vivo estimation of cerebral blood flow, oxygen consumption and glucose metabolism in the pig by [15O]water injection, [15O]oxygen inhalation and dual injections of [18F]fluorodeoxyglucose. J Neurosci Methods. 1997;77:199–209
  10. Cumming P, Danielsen EH, Vafaee M, Falborg L, Steffensen E, Sørensen JC, et al. Normalization of markers for dopamine innervation in striatum of MPTP-lesioned miniature pigs with intrastriatal grafts. Acta Neurol Scand. 2001;103:309–315
  11. Cumming P, Rosa P, Watanabe H, Smith D, Bender D, Clarke PBS, et al. Effects of acute nicotine on haemodynamics and binding of [11C]raclopride to dopamine D2,3 receptors in pig brain. Neuroimage. 2003;1127–1136
  12. Carson CC, Lue TF. Phosphodiesterase type 5 inhibitors for erectile dysfunction. BJU Int. 2005;96:257–280
  13. Corbin JD, Beasley A, Blount MA, Francis SH. High lung PDE5: a strong basis for treating pulmonary hypertension with PDE5 inhibitors. Biochem Biophys Res Commun. 2005;334:930–938
  14. Wilkins MR, Paul GA, Strange JW, Tunariu N, Gin-Sing W, et al. Sildenafil versus Endothelin Receptor Antagonist for Pulmonary Hypertension (SERAPH) study. Am J Respir Crit Care Med. 2005;171:1292–1297
  15. Shimizu-Albergine M, Rybalkin SD, Rybalkina IG, Feil R, Wolfsgruber W, Hofmann F, et al. Individual cerebellar Purkinje cells express different cGMP phosphodiesterases (PDEs): in vivo phosphorylation of cGMP-specific PDE (PDE5) as an indicator of cGMP-dependent protein kinase (PKG) activation. J Neurosci. 2003;23:6452–6459
  16. van Staveren WC, Steinbusch HW, Markerink-van Ittersum M, Behrends S, de Vente J. Species differences in the localization of cGMP-producing and NO-responsive elements in the mouse and rat hippocampus using cGMP immunocytochemistry. Eur J Neurosci. 2004;19:2155–2168
  17. Prickaerts J, Sık A, van Staveren WCG, Koopmans G, Steinbusch HWM, vander Staay FJ, et al. Phosphodiesterase type 5 inhibition improves early memory consolidation of object information. Neurochem Int. 2004;45:915–928
  18. Corbin JD, Francis SH. Pharmacology of phosphodiesterase-5 inhibitors. Int J Clin Pract. 2002;56:453–459
  19. Corbin JD, Francis SH, Webb DJ. Phosphodiesterase type 5 as a pharmacologic target in erectile dysfunction. Urol. 2002;60:4–11
  20. Saenzde Tejada I, Frutos JA, Gaudo M, Florio V. Comparative selectivity: profiles of tadalafil, sildenafil and vardenafil using an in vitro phosphodiesterase activity assay. Int J Impot Res. 2002;14:S20–S32
  21. Daugan A, Grondin P, Ruault C, Le Monnierde Gouville AC, Coste H, Linget JM, et al. The discovery of tadalafil: a novel and highly selective PDE5 inhibitor. 2: 2,3,6,7,12,12a-hexahydropyrazino[1′,2′:1,6]pyrido[3,4-b]indole-1,4-dione analogues. J Med Chem. 2003;46:4533–4542
  22. Daugan A, Grondin P, Ruault C, Le Monnier de Gouville AC, Coste H, Kirilovsky J, et al. The discovery of tadalafil: a novel and highly selective PDE5 inhibitor. 1: 5,6,11,11a-tetrahydro-1H-imidazo[1′,5′:1,6]pyrido[3,4-b]indole-1,3(2H)-dione analogues. J Med Chem. 2003;46:4525–4532
  23. Jakobsen S, Kodahl G, Cumming P, Olsen AK. Synthesis, radiolabelling and in vivo evaluation of [C-11]RAL-01 as potential phosphordiesterase PET radioligand in the pig. In:  Nyman MJ,  Oikonen V,  Turiceanu M,  Scheinin H editor. Turku PET Symposium Abstract book, Turku University. 2005;p. 63
  24. Gillings NM, Bender D, Falborg L, Marthi K, Munk OL, Cumming P. Kinetics of the metabolism of four PET radioligands in living minipigs. Nucl Med Biol. 2001;1:97–104
  25. Watanabe H, Andersen F, Simonsen CZ, Evans SM, Gjedde A, Cumming P the DaNeX Study Group. MR-based statistical atlas of the Göttingen minipig brain. Neuroimage. 2001;14:1089–1096
  26. Rosa-Neto P, Gjedde A, Olsen AK, Jensen SB, Munk OL, Watanabe H, et al. MDMA-evoked changes in [11C]raclopride and [11C]NMSP binding in living pig brain. Synapse. 2004;53:222–233
  27. Turkheimer FE, Hinz R, Cunningham VJ. On the undecidability among kinetic models: from model selection to model averaging. J Cereb Blood Flow Metab. 2003;23:490–498
  28. Pagani S, Mirtella D, Mencarelli R, Rodriguez D, Cingolani M. Postmortem distribution of sildefanil in histological material. J Anal Toxicol. 2005;29:254–257
  29. Tawakol A, Aziz K, Migrino R, Watkowska J, Zusman R, Alpert NM, et al. Effects of sildefanil on myocardial blood flow in humans with ischemic heart disease. Coron Artery Dis. 2005;17:443–449
  30. Lewis GD, Semigran MJ. Type 5 phosphodiesterase inhibition in heart failure and pulmonary hypertension. Curr Heart Fail Rep. 2004;1:183–189
  31. Lin C-S. Tissue expression, distribution, and regulation of PDE5. Int J Impot Res. 2004;16(Suppl 1):S8–S10
  32. Bender AT, Beavo JA. Specific localized expression of cGMP in Purkinje neurons and macrophages. Neurochem Int. 2004;45:853–857
  33. Gao F, Sugita M, Nukui H. Phosphodiesterase 5 inhibitor, zaprinast, selectively increases cerebral blood flow in the ischemic penumbra in the rat brain. Neurol Res. 2005;27:638–643
  34. Zhang L, Zhang RL, Wang Y, Zhang C, Zhang ZG, Meng H, et al. Functional recovery in aged and young rats after embolic stroke: treatment with a phosphodiesterase type 5 inhibitor. Stroke. 2005;36:847–852

PII: S0969-8051(06)00072-2

doi: 10.1016/j.nucmedbio.2006.04.006

Nuclear Medicine and Biology
Volume 33, Issue 5 , Pages 593-597 , July 2006

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