title: [123/125I]RTI-55, an in vivo label for the serotonin transporter.
abstract: [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.
authors.affiliation: Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
authors.forename: U
authors.initials: U
authors.lastname: Scheffel
authors.forename: R F
authors.initials: RF
authors.lastname: Dannals
authors.forename: E J
authors.initials: EJ
authors.lastname: Cline
authors.forename: G A
authors.initials: GA
authors.lastname: Ricaurte
authors.forename: F I
authors.initials: FI
authors.lastname: Carroll
authors.forename: P
authors.initials: P
authors.lastname: Abraham
authors.forename: A H
authors.initials: AH
authors.lastname: Lewin
authors.forename: M J
authors.initials: MJ
authors.lastname: Kuhar
mesh_terms: 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
chemical_list: 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