PT - JOURNAL ARTICLE AU - Yukinori Hasegawa AU - Yasukazu Kanai AU - Eku Shimosegawa AU - Masao Imaizumi AU - Jun Hatazawa TI - Microdosing study for evaluating pharmacokinetics (PK) by means of planar positron imaging system (PPIS): A comparison between microdose and therapeutic dose PK of anti-epileptic drug C-11 diphenyl hydantoin (DPH) in rats DP - 2009 May 01 TA - Journal of Nuclear Medicine PG - 1191--1191 VI - 50 IP - supplement 2 4099 - http://jnm.snmjournals.org/content/50/supplement_2/1191.short 4100 - http://jnm.snmjournals.org/content/50/supplement_2/1191.full SO - J Nucl Med2009 May 01; 50 AB - 1191 Objectives The US FDA (2006), European (2004), and Japanese (2008) regulatory authorities recommended a new approach for drug development known as microdosing with PET. In the microdosing approach, it is critically important that trace dose PK corresponds to therapeutic dose PK. We tested this assumption in rats by means of PPIS and C-11 DPH (Hasegawa Y, et al. ANM 22; 301-307:2008). Methods Fifteen male Wister rats (8 weeks old) were subdivided into 5 groups (3 rats in group A, B, C, D, and E). Two microgram of 11C-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. Results 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. 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, 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. Conclusions The present study indicated that small but significant difference between microdose and therapeutic dose PK for C-11 DPH. Research Support Research grants from the Ministry of Education, Culture, Sports, Science andTechnology (No. 1077801515), Japan