In vivo evaluation in rodents of <script type="math/tex">[^{123}I]-3-I-CO</script> as a potential SPECT tracer for the serotonin <script type="math/tex">5-HT_{2A}</script> receptor

Blanckaert, Peter M.; Burvenich, Ingrid; Wyffels, Leonie; De Bruyne, Sylvie; Moerman, Lieselotte; De Vos, Filip

doi:10.1016/J.NUCMEDBIO.2008.09.004

Title

In vivo evaluation in rodents of $[^{123}I]-3-I-CO$ as a potential SPECT tracer for the serotonin $5-HT_{2A}$ receptor

Author

Blanckaert, Peter M.

Burvenich, Ingrid

Wyffels, Leonie

De Bruyne, Sylvie

Moerman, Lieselotte

De Vos, Filip

Abstract

Introduction [123I]-(4-fluorophenyl)[1-(3-iodophenethyl)piperidin-4-yl]methanone ([123I]-3-I-CO) is a potential single photon emission computed tomography tracer with high affinity for the serotonin 5-HT2A receptor (Ki=0.51 nM) and good selectivity over other receptor (sub)types. To determine the potential of the radioligand as a 5-HT2A tracer, regional brain biodistribution and displacement studies will be performed. The influence of P-glycoprotein blocking on the brain uptake of the radioligand will also be investigated. Methods A regional brain biodistribution study and a displacement study with ketanserin were performed with [123I]-3-I-CO. Also, the influence of cyclosporin A (50 mg/kg) on the brain distribution of the radioligand was investigated. For the displacement study, ketanserin (1 mg/kg) was administered 30 min after injection of [123I]-3-I-CO. Results The initial brain uptake of [123I]-3-I-CO was quite high, but a rapid wash-out of radioactivity was observed. Cortex-to-cerebellum binding index ratios were low (1.1 1.7), indicating considerable aspecific binding and a low specific signal of the radioligand. Tracer uptake was reduced to the levels in cerebellum (a 60% reduction) after ketanserin displacement. Administration of cyclosporin A resulted in a doubling of the brain radioactivity concentration. Conclusions Although [123I]-3-I-CO showed adequate brain uptake and could be displaced by ketanserin, high aspecific binding to brain tissue was responsible for very low cortex-to-cerebellum binding index ratios, possibly limiting the potential of the radioligand as a serotonin 5-HT2A receptor tracer. We also demonstrated that [123I]-3-I-CO is probably a weak substrate for the P-glycoprotein efflux transporter.

Language

English

Source (journal)

Nuclear geophysics. - Oxford, 1993, currens

Publication

Oxford : 2008

ISSN

0969-8086 [print]

1878-6383 [online]

DOI

10.1016/J.NUCMEDBIO.2008.09.004

Volume/pages