title: Biodistribution, toxicology, and radiation dosimetry of 5-HT1A-receptor agonist positron emission tomography ligand [11C]CUMI-101.
abstract: Sprague Dawley rats (10/sex/group) were given a single intravenous (iv) dose of CUMI-101 to determine acute toxicity of CUMI-101 and radiation dosimetry estimations were conducted in baboons with [(11)C]CUMI-101. Intravenous administration of CUMI-101 did not produce overt biologically or toxicologically significant adverse effects except transient hypoactivity immediately after dose in the mid- and high-dose groups, which is not considered to be a dose-limiting toxic effect. No adverse effects were observed in the low-dose group. The no observed adverse effect level (NOAEL) is considered to be 44.05 µg/kg for a single iv dose administration in rats. The maximum tolerated dose (MTD) was estimated to be 881 µg/kg for a single iv dose administration. The Medical Internal Radiation Dose (MIRDOSE) estimates indicate the maximum permissible single-study dosage of [(11)C]CUMI-101 in humans is 52 mCi with testes and urinary bladder as the critical organ for males and females, respectively.
authors: Department of Psychiatry and Division of Molecular Imaging and Neuropathology, Columbia University Medical Center and New York State Psychiatric Institute (NYSPI), New York, NY 10032, USA. dk2038@columbia.edu
authors: Dileep J S
authors: DJ
authors: Kumar
authors: Bing
authors: B
authors: Bai
authors: Hanna H
authors: HH
authors: Ng
authors: Jon C
authors: JC
authors: Mirsalis
authors: Kjell
authors: K
authors: Erlandsson
authors: Matthew S
authors: MS
authors: Milak
authors: Vattoly J
authors: VJ
authors: Majo
authors: Jaya
authors: J
authors: Prabhakaran
authors: J J
authors: JJ
authors: Mann
authors: R V
authors: RV
authors: Parsey
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes; D005260:Female; D008024:Ligands; D008297:Male; D010215:Papio; D010879:Piperazines / Q000493:pharmacokinetics* / Q000633:toxicity; D049268:Positron-Emission Tomography; D011874:Radiometry; D051381:Rats; D017207:Rats, Sprague-Dawley; D058825:Serotonin 5-HT1 Receptor Agonists / Q000493:pharmacokinetics* / Q000633:toxicity; D014018:Tissue Distribution; D014227:Triazines / Q000493:pharmacokinetics* / Q000633:toxicity
chemical_list: C529131:2-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-4-methyl-1,2,4-triazine-3,5-(2H,4H)-dione; D002250:Carbon Radioisotopes; D008024:Ligands; D010879:Piperazines; D058825:Serotonin 5-HT1 Receptor Agonists; D014227:Triazines