Structure-localization relationships of 11C-labeled phentermine derivatives: effect of aromatic substitution.
A series of phentermine analogs, including the unsubstituted, the para-F, -Cl, -Br and -I, and the meta-CF3 derivatives, were labeled by [11C]methylation and evaluated in rats to determine the structure-localization relationships for this class of regional cerebral blood flow imaging agents. All the phentermines were well-localized in the brain; however, only the para-substituted agents were well-retained. Localization in the nontarget tissue was affected by the lipophilicity of the substituent. Comparison with the radioiodinated analogs showed virtually identical results, which suggests that the compounds were not significantly metabolized. The agent with the best biodistribution characteristics was the N-[11C]methyl-p-iodophentermine, with the p-bromo analog almost equivalent.
Elmaleh
D R
DR
Department of Radiology, Massachusetts General Hospital, Boston, 02114.
Kizuka
H
H
Hanson
R N
RN
Jones
G S
GS
Herman
L W
LW
Strauss
H W
HW
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000502:physiology; D002250:Carbon Radioisotopes; D002560:Cerebrovascular Circulation / Q000502:physiology; D007553:Isotope Labeling; D010645:Phentermine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D010645:Phentermine