Evaluation of [11C]RTI-121 as a selective radioligand for PET studies of the dopamine transporter.
The cocaine analogue RTI-121 (3 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid isopropyl ester), when labeled with carbon-11, was evaluated in rats as a potential PET ligand for the dopamine transporter. The compound gave in vivo striatum:cerebellum ratios that were similar to those obtained with the related ligand [11C]RTI-55 (2 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid methyl ester) but showed a much greater selectivity for the dopamine compared with the 5-HT uptake site. The results indicate that [11C]RTI-121 could be used in preference to [11C]RTI-55 in man. Experimentally, [11C]RTI-121 has potential in the quantification of dopamine terminal function in rat models of disease, using a combination of autoradiography, postmortem sampling, and in vivo tomography.
Hume
S P
SP
Cyclotron Unit, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Luthra
S K
SK
Brown
D J
DJ
Opacka-Juffry
J
J
Osman
S
S
Ashworth
S
S
Myers
R
R
Brady
F
F
Carroll
F I
FI
Kuhar
M J
MJ
Brooks
D J
DJ
D000818:Animals; D001711:Biotransformation; D001798:Blood Proteins / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D003042:Cocaine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D008297:Male; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods*
D001798:Blood Proteins; D002250:Carbon Radioisotopes; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C079213:RTI 121; D003042:Cocaine; D004298:Dopamine