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The 5-HT1A Receptor PET Radioligand 11C-CUMI-101 Has Significant Binding to α1-Adrenoceptors in Human Cerebellum, Limiting Its Use as a Reference Region. | LitMetric

AI Article Synopsis

Article Abstract

Unlabelled: Prazosin, a potent and selective α-adrenoceptor antagonist, displaces 25% of C-CUMI-101 ([O-methyl-C]2-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5(2H,4H)dione) binding in monkey cerebellum. We sought to estimate the percentage contamination of C-CUMI-101 binding to α-adrenoceptors in human cerebellum under in vivo conditions. In vitro receptor-binding techniques were used to measure α-adrenoceptor density and the affinity of CUMI-101 for these receptors in human, monkey, and rat cerebellum.

Methods: Binding potential (maximum number of binding sites × affinity [(1/dissociation constant]) was determined using in vitro homogenate binding assays in human, monkey, and rat cerebellum. H-prazosin was used to determine the maximum number of binding sites, as well as the dissociation constant of H-prazosin and the inhibition constant of CUMI-101.

Results: α-adrenoceptor density and the affinity of CUMI-101 for these receptors were similar across species. Cerebellar binding potentials were 3.7 for humans, 2.3 for monkeys, and 3.4 for rats.

Conclusion: Reasoning by analogy, 25% of C-CUMI-101 uptake in human cerebellum reflects binding to α-adrenoceptors, suggesting that the cerebellum is of limited usefulness as a reference tissue for quantification in human studies.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5126696PMC
http://dx.doi.org/10.2967/jnumed.116.174151DOI Listing

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