The aim of the present study was 1) to synthesize 11C-diphenylhydantoin as a specific binding marker of Na+ ion channel in myocardium, 2) to use positron planar imaging system in rats, 3) to visualize distribution and density of Na+ ion channel in rats, and 4) to analyze a difference in pharmacokinetics (PF) between therapeutic dose and microdose administration.
^<11>C was produced by means of in-house cyclotron (HM18, Sumitomo Heavy Industry Co.) with prot on beam current of 10μA and irradiation for 3 min. The nuclear reaction was 14N(p, α), which provi ded labeled precursor of ^<11>CH4,^<11>CC14, and ^<11>COC12. ^<11>COC12 was reacted with precursor of 11C-diphe nylhydantoin at 0℃ for 5min in chloroform solution. The amount of radioactivity was 1187MBq at t he end of synthesis. The radiochemical purity was 66%.
Fifteen male Wister rats (8 weeks old weighed 200〜250g) were subdivided into 5 groups (3 rats in group A, B, C, D, and E). Two □g of ^<11>C-DPH, that co-injected with 0.5mg/kg,
1.5mg/kg, 3.0mg/kg, and 25mg/kg of cold DPH were intravenously administered for group A (microdosing), B, C, D (therapeutic dosing), and E (extremely high dosing), respectively, under intraperitoneal anesthesia. Relative Uptake Value (RUV,%), defined as regional counts divided by whole body counts multiplied by 100 for initial 20min, was measured for brain, heart, liver, intestine, kidney, and urinary bladder.
During the first 20min the RUV for brain in group A, B, C, D, and E was 1.47±0.08%, 1.78±0.07%, 1.71±0.05%, 1.73±0.08%, and 2.08±0.08%, respectively. The RUV for heart in group A, B, C, D, and E was 1.51±0.20%, 1.81±0.06%, 1.95±0.05%, 1.99±0.09%, and 2.62±0.09%, respectively. In brain and heart, the RUV values of group B, C, D, and E were significantly higher than those of group A. No significant difference in RUV was found in liver, kidney, intestine, and urinary bladder.
Small but significant difference was found between microdose and therapeutic dose PK for ^<11>C-DPH. When PET microdosing is employed, the non-linearity of microdose and therapeutic dose PK should be taken into account. Less