Two new
11C-labelled ligands,
N-(3-(4-hydroxyphenyl)propyl)-3-(4-methoxyphenyl)propylamine ([
11C]2) and
N-(3-(4-hydroxyphenyl)butyl)-3-(4-methoxyphenyl)butylamine ([
11C]3) were designed based on bis(phenylalkyl)amines (1) which have been reported as polyamine site antagonists with high-selectivity for NR1A/2B NMDA receptors, and radiolabelling of the corresponding phenol precursors with [
11C]methyl iodide was readily accomplished. The
in vitro inhibition experiments using rat brain slices showed that [
11C]2 and [
11C]3 share the binding sites with spermine and/or ifenprodil but not with CP-101,606, a highly potent NR2B-selective NMDA antagonist, and that divalent cations such as Zn
2+ produced significant inhibition of both [
11C]2 and [
11C]3 bindings. Intravenous injection of [
11C]3 in mice showed almost homogenous distribution throughout the brain. Attempts to block the tracer uptake of [
11C]3 by pre-injection with the unlabelled 3 or spermine in rats were unsuccessful, but a small decrease in the cerebral uptake of [
11C]3 by co-treatment with the unlabelled 3 was observed in a monkey PET study. The present findings indicate that none of these
11C-labelled analogues have potential for PET study of binding sites on the
N-methly-
D-aspartate (NMDA) receptors.
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