Carbon-11 N-methyl alkylation of L-368,899 and in vivo PET imaging investigations for neural oxytocin receptors

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:23

Article

Smith, Aaron L.^1,2  Freeman, Sara M.¹  Voll, Ronald J.²  Young, Larry J.¹  Goodman, Mark M.² 

[1] Yerkes Natl Primate Res Ctr, Dept Psychiat & Behav Sci, Ctr Translat Social Neurosci, Atlanta, GA 30322 USA

[2] Emory Univ, Dept Radiol & Imaging Sci, Atlanta, GA 30329 USA

关键词: Oxytocin;    Vasopressin;    PET imaging;    L-368,899;    Pituitary;    Receptor imaging;   

DOI  :  10.1016/j.bmcl.2012.10.116

来源: Elsevier

【 摘 要 】

Compound L-368,899 was successfully alkylated with [C-11] iodomethane to generate the oxytocin receptor selective (2R)-2-amino-N-((2S)-7,7-dimethyl-1-(((4-(o-tolyl)piperazin-1-yl)sulfonyl)methyl) bicyclo[2.2.1]heptan-2-yl)-N-[C-11]methyl-3-(methylsulfonyl)propanamide ([C-11]1) with very high radio-chemical purity and high specific activity. PET imaging studies were performed with [C-11]1 to investigate brain penetration and oxytocin receptor uptake using rat and cynomolgus monkey models. For rat baseline scans, brain penetration was observed with [C-11]1, but no specific uptake could be distinguished in the brain region. By administering a peptide oxytocin receptor selective antagonist for peripheral blocking of oxytocin receptors, the uptake of [C-11]1 was amplified in the rat brain temporarily to enable some visual uptake within the rat brain. A baseline scan of [C-11]1 in a cynomolgus monkey model resulted in no detectable specific uptake in anticipated regions, but activity did accumulate in the choroid plexus. (c) 2012 Elsevier Ltd. All rights reserved.

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