PT - JOURNAL ARTICLE AU - Pelletier-Galarneau, Matthieu AU - Kim, Sally Ji Who AU - Petibon, Yoann AU - Guehl, Nicolas AU - Ma, Chao AU - Han, Paul AU - Martineau, Patrick AU - Normandin, Marc AU - El Fakhri, Georges AU - Alpert, Nathaniel TI - In vivo quantitative mapping of mitochondrial cardiac membrane potential: First in human<strong/> DP - 2019 May 01 TA - Journal of Nuclear Medicine PG - 99--99 VI - 60 IP - supplement 1 4099 - http://jnm.snmjournals.org/content/60/supplement_1/99.short 4100 - http://jnm.snmjournals.org/content/60/supplement_1/99.full SO - J Nucl Med2019 May 01; 60 AB - 99Background: Myocardial mitochondrial dysfunction plays a key role in many pathologic processes such as cellular apoptosis, heart failure, and ventricular arrhythmia. In normal conditions, mitochondrial membrane potential (ΔΨm) is maintained within narrow limits. Alterations in ΔΨm are a fundamental biomarker of mitochondrial and cellular dysfunction. Our group recently validated a method for in vivo assessment of cardiac ΔΨm in a porcine model (Alpert, 2018) using the fluorine-18 labeled compound 18F-triphenylphosphonium (18F-TPP+). Analysis shows that the tissue-to-plasma ratio at equilibrium, VT, is sensitive to two independent variables; the tissue fraction of the ECS (fECS) and tissue membrane potential (ΔΨT), a proxy of ΔΨm. We report the first in vivo assessment of the ΔΨT in human subjects. Methods: Seven healthy subjects were imaged using 18F-TPP+ on a Siemens Biograph PET/MR scanner. The imaging protocol consisted of a bolus injection of 300 MBq followed by a 120 min infusion of 0.6 MBq/min. A 60 min dynamic PET acquisition was started 1 hour after bolus injection. The fECS was simultaneously measured using MR T1-mapping images acquired at baseline and 15 minutes after gadolinium injection with correction for the subject’s hematocrit level. Serial venous blood samples were obtained to calculate the plasma tracer concentration. The myocardial volume of distribution, VT, was obtained by dividing the myocardial tracer concentration by the plasma concentration at secular equilibrium. ΔΨT was calculated from the VT and fECS measurements using a model based on the Nernst equation (Alpert, 2018). Results: One subject was excluded because tracer concentration equilibrium was not achieved. In the remaining subjects, secular equilibrium in plasma and myocardium was reached after approximately 90 min. Average fECS was 29.7±3.2% (range 26.1 to 33.9%). Average ventricular VT was 63.7±11.3 (range 52.3 to 85.3), yielding an average ΔΨT of -157±4 mV (range -151 to -163 mV). The parametric images were of high quality, supporting the measurement of ΔΨT to the voxel level. Conclusions: We demonstrated for the first time the feasibility of noninvasive, in vivo, quantitative assessment of cardiac ΔΨT in humans. Quantitative values of ΔΨT are in good agreement with bench top measurements in isolated mitochondria, cells and Langendorff perfused rat hearts (see Alpert et al, 2018). Currently, there are no methods for direct in vivo assessment of mitochondrial function. In vivo quantification of the mitochondrial function could provide new diagnostic and prognostic information for several cardiac diseases as well as allowing therapy monitoring. Further investigations are required to assess these potential roles. Research Support: P41EB022544 R01HL137230 T32EB013180 Acknowledgments: We thank Marina T. Macdonald-Soccorso and Julia-Ann Scotton for their essential contribution to this project.