Biodistribution, Toxicology, and Radiation Dosimetry of 5-HT1A-Receptor Agonist Positron Emission Tomography Ligand [11C]CUMI-101

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 [C-11]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 mu g/kg for a single iv dose administration in rats. The maximum tolerated dose (MTD) was estimated to be 881 mu g/kg for a single iv dose administration. The Medical Internal Radiation Dose (MIRDOSE) estimates indicate the maximum permissible single-study dosage of [C-11]CUMI-101 in humans is 52 mCi with testes and urinary bladder as the critical organ for males and females, respectively.