Abstract
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Objectives: 5-HT1A receptors exist in high and low affinity states and agonist ligands bind preferentially to the high affinity state of the receptor and provide a measure of functional 5-HT1A receptors. We report the evaluation of [O-methyl11C]2-(4-(4-(2-methoxyphenyl)6 piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3, 5(2H,4H)dione ([11C]CUMI-101) as an agonist PET tracer for 5-HT1A receptors in human.
Methods: PET scans were performed in human controls with an ECAT EXACT HR+ scanner with an i. v. bolus injection of 15.0 ± 3.0 mCi of [C-11]CUMI-101 (SA = 1.3 ± 0.2 Ci/μmol) and emission data were collected for 120 min in 3D mode. Metabolite analyses were performed using HPLC methods.
Results: PET studies in human showed that [11C]CUMI-101 penetrates the BBB and is retained in 5-HT1A receptor rich areas, whereas cerebellum had the least amount of radiotracer uptake. After 120 minutes, the ratio of counts in the regions of interest to the cerebellum was 5.8 in the entorhinal cortex, 5.6 in temporal cortex, 5.0 in the uncus, 4.8 in the anterior cingulate, 4.6 in hippocampus, 4.4 in amygdala and 3.5 in raphe nucleus. Free fraction of the tracer in human plasma was found to be 32 ± 4%. Slower metabolism was found for [11C]CUMI-101 in human plasma and the % of unmetabolized [11C]CUMI-101 was 60± 5% at 90 minutes.
Conclusions: Based on a measurable free fraction, high affinity and selectivity, adequate blood brain permeability and favorable plasma and brain kinetics, [11C]CUMI-101 is an excellent candidate for imaging high affinity 5-HT1A receptors in humans.
- Society of Nuclear Medicine, Inc.