Synthesis and in vivo brain distribution of carbon-11-labeled δ-opioid receptor agonists

Rama Pichika, Douglas M. Jewett, Philip S. Sherman, John R. Traynor, Stephen M. Husbands, James H. Woods, Michael R. Kilbourn

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Three new radiolabeled compounds, [11C]SNC80 ((+)-4-[(αR)-α-{(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl}-3-[11C]methoxybenzyl-N,N-diethylbenzamide), N,N-diethyl-4-[3-methoxyphenyl-1-[11C]methylpiperidin-4-ylidenemethyl)benzamide and N,N-diethyl-4-[(1-[11C]methylpiperidin-4-ylidene)phenylmethyl]benzamide, were prepared as potential in vivo radiotracers for the δ-opioid receptor. Each compound was synthesized by alkylation of the appropriate desmethyl compounds using [11C]methyl triflate. In vivo biodistribution studies in mice showed very low initial brain uptake of all three compounds and no regional specific binding for [11C]SNC80. A monkey positron emission tomography study of [11C]SNC80 confirmed low brain permeability and uniform regional distribution of this class of opioid agonists in a higher species. Opioid receptor ligands of this structural class are thus unlikely to succeed as in vivo radiotracers, likely due to efficient exclusion from the brain by the P-glycoprotein efflux transporter.

Original languageEnglish (US)
Pages (from-to)989-996
Number of pages8
JournalNuclear Medicine and Biology
Volume37
Issue number8
DOIs
StatePublished - Nov 2010
Externally publishedYes

Keywords

  • Emission computed
  • Opioid
  • SNC80 carbon radioisotopes
  • Tomography

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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