Evaluation of brain and whole-body pharmacokinetics of 11C-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 microg 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.
Hasegawa
Yukinori
Y
Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, Japan.
Kanai
Yasukazu
Y
Hasegawa
Shinji
S
Okamoto
Takashi
T
Matsui
Tamiko
T
Shimosegawa
Eku
E
Kurachi
Yoshihisa
Y
Hatazawa
Jun
J
D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D002250:Carbon Radioisotopes / Q000008:administration & dosage / Q000493:pharmacokinetics; D004583:Electrons; D006321:Heart / Q000000981:diagnostic imaging; D007267:Injections; D007422:Intestines / Q000000981:diagnostic imaging; D008099:Liver / Q000000981:diagnostic imaging; D008297:Male; D010672:Phenytoin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics; D051381:Rats; D014018:Tissue Distribution; D001743:Urinary Bladder / Q000000981:diagnostic imaging; D051598:Whole Body Imaging
D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D010672:Phenytoin