Development of a radioligand for imaging V1a vasopressin receptors with PET

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

Research output: Contribution to journalArticlepeer-review

Abstract

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
Volume139
DOIs
StatePublished - Oct 20 2017

Keywords

  • Positron emission tomography
  • Radiotracers
  • Vasopressin receptor

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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