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.

Figure 1

Chemical structures of CUMI-101 and [¹¹C]CUMI-101

Figure 2

Whole body [¹¹C]CUMI-101 image of baboon. Left to right: frame 1, 2, 4, 8 (Midtime 0.75, 4.38, 13.65 and 80.18 minutes) , top: coronal images, bottom: transaxial images

Figure 3

Time activity curves of [¹¹C]CUMI-101 in different organs of baboon. (The blue curves (dotted lines) are decay corrected and the red curves (dashed and solid lines) are non-decay-corrected TACs for each organ).