Title
In vivo evaluation in rodents of <tex>$[^{123}I]-3-I-CO$</tex> as a potential SPECT tracer for the serotonin <tex>$5-HT_{2A}$</tex> receptorIn vivo evaluation in rodents of <tex>$[^{123}I]-3-I-CO$</tex> as a potential SPECT tracer for the serotonin <tex>$5-HT_{2A}$</tex> receptor
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Subject
Pharmacology. Therapy
Source (journal)
Nuclear medicine and biology
Volume/pages
35(2008):8, p. 861-867
ISSN
0969-8086
ISI
000261603300006
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
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.
E-info
https://repository.uantwerpen.be/docman/iruaauth/da2486/73e4ad6c1be.pdf
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000261603300006&DestLinkType=RelatedRecords&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000261603300006&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000261603300006&DestLinkType=CitingArticles&DestApp=ALL_WOS&UsrCustomerID=ef845e08c439e550330acc77c7d2d848