RT Journal Article
SR Electronic
T1 Pharmacokinetic study of C-11 donepezil in rats measured by planar positron imaging system: A correlation between micro-dose and therapeutic dose distribution
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1767
OP 1767
VO 51
IS supplement 2
A1 Eku Shimosegawa
A1 Yasukazu Kanai
A1 Masao Imaizumi
A1 Tadashi Watabe
A1 Jun Hatazawa
YR 2010
UL http://jnm.snmjournals.org/content/51/supplement_2/1767.abstract
AB 1767 Objectives Donepezil hydrochloride (DNP) is a reversible inhibitor of acetylcholine esterase used for patients with Alzheimer’s disease. In the present study, we tested whole body pharmacokinetics of C-11 DNP in rats by means of planar positron imaging system (PPIS). Methods C-11 DNP with micro-dose (6 MBq, 10.2±5.7 ng) was injected to tail vein in six male Wister rats (weighed: 200~250g). Whole-body image acquisition started immediately after injection and continued for 40 min. Therapeutic dose study during 20 min after C-11 DNP injection was performed with co-injection of non-radioactive DNP, with varying dose from 0.05 to 0.80 mg/kg (5 groups, n=3 in each group). Relative Uptake Value (RUV%) defined as the regional radioactivity divided by the whole field-of-view radioactivity multiplied by 100 (Hasegawa Y, et al., ANM 2008), was measured for the brain, lung, liver, intestine, kidney, and urinary bladder. Results C-11 DNP accumulated predominantly in the liver and was excreted to the urinary tract and small intestine within 40 min. The RUV% of the brain at 20 min after C-11 DNP injection was 0.70±0.19 %. In the therapeutic dose study, no significant differences in RUV% were found among 5 groups in all organs. Conclusions The present results demonstrated that the pharmacokinetics of C-11 DNP was not affected under the therapeutic dose of DNP, indicating that micro-dosing test using C-11 DNP and PPIS is useful to clarify bio-distribution of DNP after therapeutic dose administration. Research Support This work was supported by research grants from the Ministry of Education, Culture, Sports, Science and Technology (No. 19591416), Japan