TY - JOUR
T1 - Synthesis and in vivo brain distribution of carbon-11-labeled δ-opioid receptor agonists
AU - Pichika, Rama
AU - Jewett, Douglas M.
AU - Sherman, Philip S.
AU - Traynor, John R.
AU - Husbands, Stephen M.
AU - Woods, James H.
AU - Kilbourn, Michael R.
N1 - Funding Information:
This work was supported by grants form the National Institutes of Health ( DA00254 , MH47611 ), NIH training grant T32-CA09015 (to R.P.), and the Office of Science (BER), U.S. Department of Energy , Grant No. DE-FG02-87ER60561 .
PY - 2010/11
Y1 - 2010/11
N2 - 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.
AB - 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.
KW - Emission computed
KW - Opioid
KW - SNC80 carbon radioisotopes
KW - Tomography
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U2 - 10.1016/j.nucmedbio.2010.06.002
DO - 10.1016/j.nucmedbio.2010.06.002
M3 - Article
C2 - 21055630
AN - SCOPUS:78049466151
VL - 37
SP - 989
EP - 996
JO - International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology
JF - International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology
SN - 0969-8051
IS - 8
ER -