In vivo evaluation of radioiodinated o-iodo-trans-decalinvesamicol (OIDV) as a vesicular acetylcholine transporter (VAChT) imaging agent

Objectives We focused on the vesicle acetyl choline transporter (VAChT) which was suggested that decreases in the brain of early Alzheimer’s disease. Vesamicol is known to have high affinity to not only VAChT but also sigma receptors (σ-1 and σ-2). Our previous in vitro study revealed that a vesamicol analog, o-iodo-trans-decalinvesamicol (OIDV) showed greater binding affinity to VAChT than did vesamicol with low affinity of OIDV to σ receptors. In this study, we performed in vivo evaluation of [125I]OIDV as a potential VAChT imaging probe.

Methods [125I]OIDV was prepared from o-tributylstannyl-trans-decalinvesamicol(OTDV) by iododestannylation reaction under no-carrier-added conditions. [125I]OIDV was injected I/V into rats. The rats were sacrificed at 10, 30, 60 and 120 min postinjection and interest organs were collected, weighed and counted to investigate the biodistribution. In vivo blocking study were performed to reveal the binding selectivity of [125I]OIDV to VAChT in vivo. Ex vivo autoradiography were performed to reveal the regional brain distribution of [125I]OIDV at 60 min postinjection.

Results Biodistribution study showed considerable uptake (about 0.4 %ID/g) of [125I]OIDV in brain at 60 min postinjection. The uptake of [125I]OIDV in brain was blocked by about 60 and 80% respectively by coadministration of 0.125 and 0.250 µmol veamicol (VAChT ligand) in in vivo blocking study. On the other hand, Blocking of the uptake of [125I]OIDV in brain was not observed significantly by coadministration of 0.125 µmol pentazocine (σ-1 receptor ligand), 3-PPP (σ-1 ,2 ligand). In ex vivo autoradiography, accumulation of [125I]OIDV in striatum and cortex was observed visually.

Conclusions These results showed that [125I]OIDV bound selectively to VAChT in rat brain in vivo. Radioiodinated OIDV labeled with 123I was suggested to be useful as a VAChT imaging agent for SPECT.