In vivo evaluation in rodents of [(123)I]-3-I-CO as a potential SPECT tracer for the serotonin 5-HT(2A) receptor.
BACKGROUND
[(123)I]-(4-fluorophenyl)[1-(3-iodophenethyl)piperidin-4-yl]methanone ([(123)I]-3-I-CO) is a potential single photon emission computed tomography tracer with high affinity for the serotonin 5-HT(2A) receptor (K(i)=0.51 nM) and good selectivity over other receptor (sub)types. To determine the potential of the radioligand as a 5-HT(2A) 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 [(123)I]-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 [(123)I]-3-I-CO.


RESULTS
The initial brain uptake of [(123)I]-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 [(123)I]-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-HT(2A) receptor tracer. We also demonstrated that [(123)I]-3-I-CO is probably a weak substrate for the P-glycoprotein efflux transporter.
Blanckaert
Peter B M
PB
Laboratory for Radiopharmacy, Ghent University, B-9000 Ghent, Belgium. peter.blanckaert@hotmail.com
Burvenich
Ingrid
I
Wyffels
Leonie
L
De Bruyne
Sylvie
S
Moerman
Lieselotte
L
De Vos
Filip
F
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology; D000818:Animals; D001921:Brain / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D007457:Iodine Radioisotopes; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D019275:Radiopharmaceuticals / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000032:analysis*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D044402:Receptor, Serotonin, 5-HT2A; D016572:Cyclosporine; D007650:Ketanserin