PT - JOURNAL ARTICLE AU - Ali Bonab AU - Gaofeng Zhao AU - Timothy Shoup AU - David Elmaleh AU - Ronald Tompkins AU - Alan Fischman TI - Membrane potential-dependent uptake of the <sup>18</sup>F-triphenylphosphonium - A new voltage sensor for detecting mitochondrial dysfunction after burn injury DP - 2013 May 01 TA - Journal of Nuclear Medicine PG - 1207--1207 VI - 54 IP - supplement 2 4099 - http://jnm.snmjournals.org/content/54/supplement_2/1207.short 4100 - http://jnm.snmjournals.org/content/54/supplement_2/1207.full SO - J Nucl Med2013 May 01; 54 AB - 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&lt;0.01). The results with 18F-TTP and 3H-TPP were highly correlated. Burn injury induced significant reductions of 18F-TPP uptake in heart, lung, liver and spleen which presented remarkable amounts of apoptosis. Conclusions 18F-TTP is a promising new voltage sensor for detecting mitochondrial dysfunction, and burn-induced apoptotic status in organs.