Imaging mitochondrial membrane potential using a novel ¹⁸F-labeled BMS derivative (¹⁸F-FP10X)

Objectives Mitochondrial membrane potential (MMP) is a reliable index of status of mitochondrial function. We developed a novel myocardial perfusion tracer, a ¹⁸F-labeled BMS derivative (¹⁸F-FP10X) with a triazole group.It is a cation, we hypothesized that ¹⁸F-FP10X might be a candidate for imaging MMP. Thus, in cellular level, we investigated correlation of uptake of this tracer with MMP.

Methods Cultured myocardial fibroblast cells were employed. MMP fluorescence probe,TRMR(tetramethyl rhodamine methyl ester), was used to measure MMP using a laser confocal microscope(LCM) and flow cytometry(FC). ¹⁸F-FP10X was obtained from myocardial perfusion research group. CCCP(carbonyl cyanide m-chlorophenyl hydrazone) and valinomycin were used as MMP uncouplers. MMP was estimated as MMP=-60*log(7.6*Cmito/Ccyto),where Cmito was the TRMR concentration in mitochondria and Ccyto in cytosol, 60,a constant for TRMR,and 7.6,a recovery factor for mitochondria.

Results When CCCP was added to cultured fibroblast cells at 0.1µM and 1µM:1) uptake of tracer decreased by 24.6% and 30.6%, respectively;2) cells were depolarized from -103mV to -94.5mV and -89.5mV (LCM);3) TRMR intensity decreased by 13.1% and 18.6% (FC). When valinomycin was added at 1nM and 5nM;1) uptake of tracer was decreased by 25.3% and 38.7%;2) cells were depolarized from -103mV to -76.9mV and -65.2mV;3) TRMR intensity was decreased by 26.5% and 24.8% (FC). Combining tracer uptake with LCM data, the relation of tracer uptake with MMP was 100% (-103mV), 75.4% (-94.5mV), 69.4% (-89.5mV), 74.7% (-76.9mV) and 61.3% (-65.2mV).

Conclusions This preliminary cellular study demonstrates that the novel myocardial perfusion-aimed ligand, ¹⁸F-FP10X, can be used for imaging mitochondrial membrane potential.

Research Support This work was supported by the NNSF of China (No.81360226).