Evaluation of brain and whole-body pharmacokinetics of 11 C-labeled diphenylhydantoin in rats by means of planar positron imaging system

Objective A planar positron imaging system (PPIS) enables whole-body dynamic imaging of radiopharmaceuticals labeled with positron-emitting nuclides. We evaluated the difference in the brain and whole-body pharmacokinetics of 11 C-diphenylhydantoin ( 11 C-DPH) between intravenous and duodenal administration in rats. Methods Male Wistar rats (8 weeks old, mean body weight 250 g) were examined under anesthesia. A tracer amount of 11 C-DPH (2 μg or less; about 5 MBq) was injected into the tail vein ( n = 3) or duodenum ( n = 3). Immediately following the administration, PPIS scans were obtained for 20 min. Regions of interest (ROIs) were set on the brain, heart, liver, intestinal field, and urinary bladder, identified on the integrated images. The relative uptake value (RUV, %) was calculated as the regional count divided by the whole-body count multiplied by 100. Sequential changes in the RUV for each ROI were analyzed for the brain and other organs. Results Following intravenous injection of 11 C-DPH, the RUV in the brain was 1.59 ± 0.07%, 1.53 ± 0.09%, 1.40 ± 0.09%, and 1.38 ± 0.08% at 5 min, 10 min, 15 min, and 20 min after the injection, respectively. After duodenal administration, the corresponding values were 0.54 ± 0.16%, 1.01 ± 0.12%, 1.43 ± 0.24%, and 1.52 ± 0.06%, respectively. The 11 C-DPH distribution was significantly lower at 5 min and 10 min following duodenal administration than after intravenous injection ( P < 0.01). Radioactivity in the urinary bladder was identified by 20 min after both intravenous injection and duodenal administration. Conclusions The present study demonstrated a difference in the brain distribution of 11 C-DPH between intravenous and duodenal administration in rats. Use of the PPIS is feasible for the evaluation of the pharmacokinetics in both the target organ and the whole body in small animals.