RT Journal Article SR Electronic T1 Kinetic Modeling and Quantitative Mapping of Membrane Potential JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP 360 OP 360 VO 58 IS supplement 1 A1 Nathaniel Alpert A1 Nicolas Guehl A1 Leon Ptaszek A1 Dustin Wooten A1 Chao Ma A1 Kasue Takahashi A1 Paul Han A1 Timothy Shoup A1 Marc Normandin A1 Georges El Fakhri YR 2017 UL http://jnm.snmjournals.org/content/58/supplement_1/360.abstract AB 360Objectives: Maintenance of membrane potential in a narrow range is essential for mitochondrial function. Prior research has established that abnormalities in mitochondrial membrane potential are tightly correlated with mitochondrial dysfunction; but currently, there are no noninvasive methods for assessing the status of mitochondria. The goal of this abstract is to communicate initial studies in lung, liver, heart and muscle within the context of advances in the kinetic modeling of the dependence of tissue concentration of lipophilic cations on membrane potential.Methods: The kinetics of 18F-labeled tetraphenylphosphonium, 18F-TPP+, were measured for 120 minutes after bolus injection or primed-constant infusion in the liver, lung, skeletal muscle and heart of 9 domestic swine using PET/CT or PET/MR. The Nernst equation relates the equilibrium concentrations of TPP+ on both sides of a permeable membrane to the membrane’s electric potential. We describe the PET concentration of 18F-TPP+ in terms of its distribution in extracellular (ECS), cytosolic (cyto) and mitochondrial (mito) spaces. The volume of distribution, VT, was determined from PET kinetic curves, and partitioned as, VT = VECS+Vcyto+Vmito. Fractional ECS volumewas measured by CT or MR.Results: A simplified and approximate equation for membrane potential is given by VT=(1-fECS )∙fmito∙e-βΔΨ, where β is a product of physical constants, fECS and fmito are respectively tissue and mitochondrial volume fractions, and ΔΨ is the total membrane potential. Due to the exponential dependence, normal TPP+ concentration in mitochondria can be very high, 1000 X plasma concentration, and VT can be greater than 30. This equation also makes clear that the distribution of TPP+ depends on the volume of extracellular space, a potentially confounding factor which can vary with age and disease. The bar graph summarizes the average value of membrane potential in heart, muscle, liver and lung and shows that ΔΨ is relatively constant in different tissue types, despite a 10-fold variation in mitochondrial volume fraction.Conclusion: The results of these studies deepen our understanding of the uptake of lipophilic cations--The equilibrium tissue-to-plasma ratio (VT) is critical. Our data support the feasibility of measuring tissue membrane potential and suggest that with further development and validation, translation to noninvasive studies in human subjects may also be feasible. Research Support: This work was supported in part by NIH grant: R01HL110241 $$graphic_5AF9740C-798E-450A-8666-45CF169698B1$$