title: Development of acute and subacute toxicity with the serotonin transporter radiopharmaceutical, ADAM.
abstract: It is predicted that depression will become the most common neurological disease in the new millennium. Its incidence is currently about 3% of diseases worldwide. Serotonin is an essential neurotransmitter for the central and peripheral nervous systems and plays a crucial role in neuropsychiatric disorders. (123)I-labeled ADAM was developed to facilitate an early diagnosis of serotonin transporter (SERT) abnormalities in the brain. Many studies have confirmed that the binding of this radiotracer to SERTs is associated with depression. The aim of this study was to evaluate the acute and subacute toxicity of ADAM and to determine its no observed adverse effect level (NOAEL) by administering it via intravenous injection to Sprague-Dawley rats for 14 consecutive days. None of the animals died, and no treatment-related clinical signs were observed. Urinalysis, hematology, and clinical chemistry analysis revealed that daily administration of ADAM (2-2-dimethylaminomethylphenylthio-5-iodophenylamine) for 2 weeks had no toxicological effects. It is concluded that ADAM exerts no adverse toxic effects on this animal model. The NOAEL was 155 microg/kg/day.
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kang-Wei
authors.initials: KW
authors.lastname: Chang
authors.forename: Chia-Chieh
authors.initials: CC
authors.lastname: Chen
authors.forename: Shih-Ying
authors.initials: SY
authors.lastname: Lee
authors.forename: Lie-Hang
authors.initials: LH
authors.lastname: Shen
authors.forename: Hsin-Ell
authors.initials: HE
authors.lastname: Wang
mesh_terms: D000818:Animals; D002928:Cinanserin / Q000031:analogs & derivatives* / Q000633:toxicity; D005260:Female; D007457:Iodine Radioisotopes; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D019275:Radiopharmaceuticals / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D023382:Toxicity Tests, Acute; D036401:Toxicity Tests, Chronic
chemical_list: C413491:2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins; D002928:Cinanserin