Development of a radioligand for imaging V1a vasopressin receptors with PET

Ravi Naik, Heather Valentine, Andrew Hall, William B Mathews, James C O Harris, C. Sue Carter, Robert F Dannals, Dean Foster Wong, Andrew Horti

Research output: Contribution to journalArticle


A series of vasopressin receptor V1a ligands have been synthesized for positron emission tomography (PET) imaging. The lead compound (1S,5R)-1 ((4-(1H-indol-3-yl)-3-methoxyphenyl) ((1S,5R)-1,3,3-trimethyl-6-azabicyclo[3.2.1]octan-6-yl)methanone) and its F-ethyl analog 6c exhibited the best combination of high binding affinity and optimal lipophilicity within the series. (1S,5R)-1 was radiolabeled with 11C for PET studies. [11CH3](1S,5R)-1 readily entered the mouse (4.7% ID/g tissue) and prairie vole brains (∼2% ID/g tissue) and specifically (30–34%) labeled V1a receptor. The common animal anesthetic Propofol significantly blocked the brain uptake of [11CH3](1S,5R)-1 in the mouse brain, whereas anesthetics Ketamine and Saffan increased the uptake variability. Future PET imaging studies with V1a radiotracers in non-human primates should be performed in awake animals or using anesthetics that do not affect the V1a receptor.

Original languageEnglish (US)
Pages (from-to)644-656
Number of pages13
JournalEuropean Journal of Medicinal Chemistry
Publication statusPublished - Oct 20 2017



  • Positron emission tomography
  • Radiotracers
  • Vasopressin receptor

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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