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

Department of Radiology, University of California, San Diego, CA, USA. rpichika@ucsd.edu

Nuclear medicine and biology 2010 Nov

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Three new radiolabeled compounds, [(11)C]SNC80 ((+)-4-[(αR)-α-{(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl}-3-[(11)C]methoxybenzyl-N,N-diethylbenzamide), N,N-diethyl-4-[3-methoxyphenyl-1-[(11)C]methylpiperidin-4-ylidenemethyl)benzamide and N,N-diethyl-4-[(1-[(11)C]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 [(11)C]methyl triflate. In vivo biodistribution studies in mice showed very low initial brain uptake of all three compounds and no regional specific binding for [(11)C]SNC80. A monkey positron emission tomography study of [(11)C]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. Copyright © 2010 Elsevier Inc. All rights reserved.

Citation

Rama Pichika, Douglas M Jewett, Philip S Sherman, John R Traynor, Stephen M Husbands, James H Woods, Michael R Kilbourn. Synthesis and in vivo brain distribution of carbon-11-labeled δ-opioid receptor agonists. Nuclear medicine and biology. 2010 Nov;37(8):989-96