Preparation and biodistribution of 1-[2-(3-[125I]iodo-4-aminophenyl)ethyl]-4-[3-(trifluoromethyl) phenyl]piperazine and 1-[2-(3-[125I]iodo-4-azidophenyl)ethyl]-4-[3-(trifluoromethyl)phenyl] piperazine.
The iodinated analogue of 1-[2-(4-aminophenyl)ethyl]-4-[3-(trifluoromethyl)phenyl]piperazine (PAPP), IPAPP (4), and the corresponding azido compound azido-IPAPP (5) were synthesized. The corresponding no-carrier-added 125I (T1/2 = 60 days, 35-60 keV) labeled compounds were also prepared. High specific binding was observed from in vitro binding studies using rat brain tissue preparation; Ki = 20 and 17.5 nM against [3H]-5-HT. In vivo biodistribution studies in rats showed that azido-[125I]IPAPP passed through intact blood-brain barrier and localized in the brain. Ex vivo autoradiography of rat brain sections exhibited a diffuse uptake pattern, which may be due to specific and nonspecific binding. The results indicate that IPAPP and azido-IPAPP may not be suitable to image the serotonin receptor in the brain.
Chumpradit
S
S
Department of Radiology, University of Pennsylvania, Philadelphia 19104.
Kung
H F
HF
Billings
J
J
Guo
Y Z
YZ
Wu
Y
Y
Shih
J
J
D000818:Animals; D001345:Autoradiography; D001386:Azides / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D002417:Cattle; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D008297:Male; D010879:Piperazines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism; D014018:Tissue Distribution
D001386:Azides; D007457:Iodine Radioisotopes; D010879:Piperazines; D011985:Receptors, Serotonin; C058709:1-(2-(3-iodo-4-aminophenyl)ethyl)-4-(3-(trifluoromethyl)phenyl)piperazine; C058710:1-(2-(3-iodo-4-azidophenyl)ethyl)-4-(3-(trifluoromethyl)phenyl)piperazine