Novel PET Probes 18F-BCPP-EF and 18F-BCPP-BF for Mitochondrial Complex I: A PET Study in Comparison with 18F-BMS-747158-02 in Rat Brain

Journal of Nuclear Medicine

Dai Fukumoto¹  Norihiro Harada¹  Hideo Tsukada¹  Masakatsu Kanazawa¹  Shingo Nishiyama¹ 

[1] Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan Central Research Laboratory, Hamamatsu Photonics K.K., Hamamatsu, Shizuoka, Japan

关键词: mitochondria complex I;    brain;    ischemia;    ¹⁸F-BCPP-EF;    PET;   

DOI  :  10.2967/jnumed.113.125328

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

We developed novel PET probes, 2-tert-butyl-4-chloro-5-{6-[2-(2-18F-fluoroethoxy)-ethoxy]-pyridin-3-ylmethoxy}-2H-pyridazin-3-one (18F-BCPP-EF) and 2-tert-butyl-4-chloro-5-[6-(4-18F-fluorobutoxy)-pyridin-3-ylmethoxy]-2H-pyridazin-3-one (18F-BCPP-BF), for quantitative imaging of mitochondrial complex I (MC-I) activity in the brain and preliminarily evaluated their properties in comparison with 18F-BMS-747158-02 (18F-BMS). Methods: The affinity of 18F-BCPP-EF, 18F-BCPP-BF, and 18F-BMS to MC-I was analyzed using in vitro binding assays with 3H-dihydrorotenone and bovine cardiomyocyte submitochondrial particles. 18F-BCPP-EF, 18F-BCPP-BF, or 18F-BMS was intravenously injected into rats, and the uptake (standardized uptake value) in each organ was determined by dissection method. The effects of rotenone, a specific MC-I inhibitor, on the uptake of each probe were assessed by whole-body PET imaging in rats. Ischemic brain model rats were imaged using 18F-BCPP-EF. Results: The rank order of affinity to MC-I was 18F-BCPP-BF > 18F-BMS > 18F-BCPP-EF. The uptake of 18F-BCPP-EF and 18F-BMS was high in the heart, intermediate in brain, and low in muscle and bone 60 min after the injection. 18F-BCPP-BF provided increasing bone uptake with time after the injection. The uptake of 18F-BCPP-EF and 18F-BMS into the brain and heart was significantly decreased by preadministration of rotenone; however, the reduction degree of 18F-BCPP-EF was more pronounced than that of 18F-BMS. Rotenone did not affect 18F-BCPP-BF uptake in either the brain or the heart. 18F-BCPP-EF imaged the cortical ischemic neuronal damage without any disturbance by microglial activation even on day 7 when 18F-FDG showed high uptake in the damaged area. Conclusion: The present study demonstrated that 18F-BCPP-EF could be a potential PET probe for quantitative imaging of MC-I activity and its ischemic damage in the living brain with PET.

【 授权许可】

Unknown