[123/125I]RTI-55, an in vivo label for the serotonin transporter.
[123I]RTI-55, an iodinated derivative of the cocaine analog 3 beta-phenyltropane-2 beta-carboxylic acid methyl ester, was evaluated as an agent for in vivo labeling of the serotonin transporter. Labeling of the precursor of RTI-55 with I-123 was efficient and yielded a high specific activity product. After intravenous injection of [123I]RTI-55 into rats, the tracer accumulated in regions with high densities of serotonin and dopamine uptake sites. The distribution of [123I]RTI-55 binding in areas rich in serotonin uptake sites correlated with [3H]serotonin uptake measured in vitro in the same regions. Specific [123I]RTI-55 binding to serotonin uptake sites was inhibited by paroxetine but not by GBR 12,909. Treatment of rats with neurotoxic doses of fenfluramine caused decreases of 66% (in the hypothalamus) to 83% (in the superior colliculi) of specific [125I]RTI-55 binding in all areas except in the striatum and the olfactory tubercles (regions rich in dopamine transporters). These results indicate that [123/125I]RTI-55 binds, although not selectively, to the serotonin transporter in vivo. Furthermore, they suggest that [123I]RTI-55 holds promise as a SPECT imaging agent for the study of the serotonin transporter in humans in health and disease.
Scheffel
U
U
Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Dannals
R F
RF
Cline
E J
EJ
Ricaurte
G A
GA
Carroll
F I
FI
Abraham
P
P
Lewin
A H
AH
Kuhar
M J
MJ
D000818:Animals; D001693:Biological Transport, Active; D003042:Cocaine / Q000031:analogs & derivatives*; D005277:Fenfluramine / Q000494:pharmacology; D006651:Histocytochemistry; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D008297:Male; D017374:Paroxetine; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D015899:Tomography, Emission-Computed, Single-Photon
D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D010880:Piperidines; D012702:Serotonin Antagonists; D005277:Fenfluramine; D012701:Serotonin; D017374:Paroxetine; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D003042:Cocaine