In collaboration with the Managers of Molecular Imaging Laboratories (MOMIL) Interest Group of the World Molecuar Imaging Society, the PET Radiotracer Translation and Resource Center (PET-RTRC) is hosting a webinar featuring Georges El Fakhri, PhD, and moderated by Robert J. Gropler, MD.
El Fakhri is the Nathaniel & Diana Alpert Professor of Radiology and director of the Gordon Center for Medical Imaging at Massachusetts General Hospital and Harvard Medical School. Gropler is the program director of the PET-RTRC and senior vice chair and division director of radiological sciences at MIR.
El Fakhri will present “In Vivo Quantitative Mapping of Cardiac Membrane Potential.” The live webinar will take place on Aug. 12 at 1 p.m. EST.
About the Lecture: Mitochondrial dysfunction plays a key role in many cardiac disorders, such as heart failure, ventricular arrhythmia, and chemotherapy-induced cardiotoxicity. Consequently, non-invasive assessment of mitochondrial function could provide an important biomarker for evaluating those diseases very early on and enable therapy monitoring. The mitochondrial membrane potential (ΔΨm), an electric field maintained across the inner mitochondrial membrane, is a comprehensive index of mitochondrial function. Until recently, measurement of ΔΨm was only feasible in vitro.
In this talk, we describe the approach we have developed for mapping the cardiac tissue membrane potential, ΔΨT, a proxy of ΔΨm, non-invasively in vivo with [18F](4-Fluorophenyl)triphenylphosphonium ([18F]FTPP+) and PET. [18F]FTPP+ is a lipophilic cationic tracer that distributes in the cardiomyocyte cytosol and mitochondria according to the cellular and mitochondrial membrane potential. We have shown in large-animal and human studies that measuring ΔΨT with [18F]FTPP+ PET is feasible with excellent agreement of the corresponding ΔΨm with values from the literature as well as very low test-retest variability within and across subjects. Furthermore, we have confirmed in vivo that the measured myocardial [18F]FTPP+ uptake is indeed sensitive to changes in ΔΨm.
Our approach has a range of potential clinical applications. For example, in a first proof-of-principle study in swine, we have demonstrated that [18F]FTPP+ PET can detect an acute partial depolarization of ΔΨm following myocardial exposure to doxorubicin, a common chemotherapeutic with known cardiotoxicity, thus indicating our approach’s potential for early assessment of doxorubicin-induced cardiotoxicity and improved chemotherapy-monitoring.