Mechanism of uptake and retention of F-18 BMS-747158-02 in cardiomyocytes: A novel PET myocardial imaging agent

Abstract

F-18 BMS-747158-02 is a novel positron emission tomography cardiac tracer targeting MC-I in cardiomyocytes with rapid uptake and slow washout. These characteristics allow fast and sustained accumulation in the heart.

Novel PET Probes18F-BCPP-EF and18F-BCPP-BF for Mitochondrial Complex I: A PET Study in Comparison with18F-BMS-747158-02 in Rat Brain

“…The accumulation of 18 F-BMS was reported to depend on cellular MC-I activity, which is the first component of 4 electron transport complexes in the inner mitochondrial membrane (17,18). By an in vitro assay in a monolayer of neonatal rat cardiomyocytes, it was confirmed that 18 F-BMS uptake was inhibited by rotenone, a specific MC-I inhibitor (17).…”

“…The present study evaluated the capability of 18 F-BCPP-EF and 18 F-BCPP-BF (20) as PET probes for imaging the MC-I activity in the living rat brain in comparison with a previously reported probe 18 F-BMS (17,18).…”

“…Radioactivity yields, radiochemical yields, radiochemical purities, and specific radioactivities of 18 F-BCPP-EF and 18 F-BCPP-BF were 5.1 6 0.9 and 3.7 6 1.1 GBq (mean 6 SD, n 5 5), 30.8 6 4.2 and 16.3% 6 2.7%, 99.1 6 0.7 and 99.6% 6 0.6%, and 139.6 6 37.0 and 111.8 6 40.1 GBq/mmol, respectively. 18 F-BMS was labeled as reported previously (17,18). Radioactivity yield, radiochemical yield, radiochemical purity, and specific radioactivity were 4.7 6 1.0 GBq, 19.1% 6 3.7%, 99.6% 6 0.7%, and 67.2 6 17.6 GBq/mmol, respectively.…”

“…For the quantitative neuroimaging of normal tissues without interference by neuroinflammation, we proposed to apply a specific PET probe for MC-I, 18 F-BMS-747158-02 ( 18 F-BMS) (16), which was originally developed as a myocardial perfusion imaging agent (17,18). Because whole-body PET imaging indicated high uptake and long retention not only in heart but also in the brain (17), we hypothesized that 18 F-BMS might be applicable for detecting neuronal damage in the living brain using PET.…”

“…Because whole-body PET imaging indicated high uptake and long retention not only in heart but also in the brain (17), we hypothesized that 18 F-BMS might be applicable for detecting neuronal damage in the living brain using PET. In fact, we demonstrated that 18 F-BMS might be useful to detect ischemic neuronal damage at the subacute phase 7 d after ischemic insult (16), at which time markedly higher uptake of 18 F-FDG, induced by microglial activation, was observed in the ischemic area (12,16).…”