@article{oai:repo.qst.go.jp:00045806,
 author = {Kawamura, Kazunori and Konno, Fujiko and Yui, Joji and Yamasaki, Tomoteru and Hatori, Akiko and Yanamoto, Kazuhiko and Wakizaka, Hidekatsu and Takei, Makoto and Nengaki, Nobuki and Fukumura, Toshimitsu and Zhang, Ming-Rong and 河村 和紀 and 昆野 富士子 and 由井 譲二 and 山崎 友照 and 羽鳥 晶子 and 柳本 和彦 and 脇坂 秀克 and 武井 誠 and 念垣 信樹 and 福村 利光 and 張 明栄},
 issue = {5},
 journal = {Annals of Nuclear Medicine},
 month = {Jun},
 note = {Objective  
XR9576 (tariquidar) is an anthranilic acid derivative and potent P-glycoprotein (P-gp) inhibitor. XR9576 has undergone phase I and II studies as combined chemotherapy against cancer. XR9576 has been developed as a useful therapeutic agent but not as a PET probe. We therefore developed [11C]XR9576 as a PET probe and assessed whether PET studies using [11C]XR9576 are a promising approach to assess P-gp function primarily. 
Methods  
We synthesized [11C]XR9576 by methylation of 7-O-desmethyl XR9576 with [11C]methyl iodide. In in vivo tissue distribution, the effects of co-injection with XR9576 on the uptake of [11C]XR9576 in mice were investigated. PET studies using [11C]XR9576 were performed in P-gp and/or Bcrp knockout mice as well as in wild-type mice. Metabolites of [11C]XR9576 were measured in the brain and plasma of mice. 
Results  
[11C]XR9576 was successfully synthesized with suitable radioactivity for injection as well as appropriate radiochemical purity and stability. In in vivo tissue distribution, the brain uptake of [11C]XR9576 significantly increased about tenfold of control on co-injection with >10 mg/kg of XR9576. In PET studies, the AUCbrain [0–60 min] in P-gp and P-gp/Bcrp knockout mice was 2- and 11-fold higher than that in wild-type mice. [11C]XR9576 showed a high metabolic stability (>90% unchanged form) in the brain and plasma of mice 30 min after injection. These results suggest that a tracer amount of [11C]XR9576 behave as the P-gp and Bcrp substrate, and the increased brain uptake or AUCbrain of [11C]XR9576 correlates with P-gp and Bcrp functions. 
Conclusions  
PET studies using [11C]XR9576 may be a promising approach for evaluating deficiency of the function of drug efflux transporters targeting intracranial diseases and tumors.},
 pages = {403--412},
 title = {Synthesis and evaluation of [11C]XR9576 to assess the function of drug efflux transporters using PET},
 volume = {24},
 year = {2010}
}