Membrane potential-dependent uptake of the 18F-triphenylphosphonium - A new voltage sensor for detecting mitochondrial dysfunction after burn injury

1207 Objectives Mitochondrial dysfunction has been closely related to many physiological and pathological processes, such as cellular apoptosis. Alterations in organelle membrane potential trigger mitochondrial dysfunction. 18F- triphenylphosphonium (18F-TTP), is a mitochondria-targeting radiopharmaceutical agent. We hypothesized that the uptake of 18F-TTP might be used to detect the functional status of mitochondria and apoptosis. Methods In the current study, we used the PC-3 cell line to assess the uptake of 18F-TTP co-administered with the the standard voltage sensor 3H-tetraphenylphosphonium (3H-TPP) ex vivo measured under various conditions that are well known to alter mitochondrial membrane potential : different extra-cellular K concentrations, carbonyl cyanide m-chlorophenylhydrazone (CCCP) incubation, and staurosporine. For in vivo studies, groups of 6 C57/BL6 mice were subjected to full thickness 30% total body burn injury, on their backs. At 24h after injury the mice were injected with 100μCi of 18F-TTP and biodistribution was measured. Results We found that stepwise membrane depolarization by K resulted in a linear decrease in 18F-TTP cellular uptake, with a slope 0.64±0.07 and a correlation coefficient of 0.92±0.08. Stepwise selective collapse of mitochondria membrane potential by CCCP treatment caused a substantial decrease in cellular uptake for 18F-TTP compared with control. Exposure to staurosporine, which is known to collapse mitochondrial membrane potential, lead to a remarkable decrease in 18F-TTP uptake compared with control (15.7±3.8% v.s 4.5±1.2%, p Conclusions 18F-TTP is a promising new voltage sensor for detecting mitochondrial dysfunction, and burn-induced apoptotic status in organs.