RT Journal Article
SR Electronic
T1 Measurement of Myocardial MembranePotential by Primed Constant Infusion
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 258
OP 258
VO 60
IS supplement 1
A1 Sally Kim
A1 Matthieu Pelletier-Galarneau
A1 Yoann Petibon
A1 Tao Sun
A1 Patrick Martineau
A1 Marc Normandin
A1 Georges El Fakhri
A1 Nathaniel Alpert
YR 2019
UL http://jnm.snmjournals.org/content/60/supplement_1/258.abstract
AB 258Introduction: We recently reported a bolus method with dynamic imaging 18F-TPP+ (18F-labeled tetraphenylphosphonium) for measuring the tissue membrane potential (ΔΨT), a proxy for the mitochondrial membrane potential (ΔΨm) [1]. The total volume of distribution (VT) of 18F-TPP+ is sensitive to two independent variables; the tissue fraction of the extra-cellular space (fECS) and tissue membrane potential (ΔΨT). The original methodology [1] requires imaging with blood sampling for 120 minutes. This study reports a new methodology, using bolus plus infusion, referred as primed constant infusion, of 18F-TPP+ to image a steady state which is more suitable for human investigation. Furthermore, we tested the hypothesis that intra-coronary infusion of BAM15, a mitochondrial proton gradient uncoupler [2,3], during imaging depolarizes myocardium membrane potential resulting in lower 18F-TPP+ concentration in relevant heart segments. Methods: Four mini-pigs (three normal and one pig with myocardial infarction) were administered 18F-TPP+ by intravenous bolus injection followed by a constant infusion for up to 180 min. A PET/CT (GE Discovery MI) scanner was used to measure dynamic 18F-TPP+ during the experimental period. And whole blood and plasma activity concentration history was also obtained. Pre-contrast and post-contrast CT scans [4] were used to produce a map of fECS. VT and ΔΨT were measured at secular equilibrium (90-105 min). After 105 min, BAM15 was infused into the left anterior descending (LAD) coronary artery for 25 min. Two pig studies were used to establish BAM15 dosing and two pigs were studied with the complete protocol. Tissue-to-plasma concentration at equilibrium, VT, was determined using 17 segment polar mapping. Results: The average fECS map value was 24.2±2.5%. The quality of fECS maps is adequate for calculation of ΔΨT. During the “control” secular equilibrium state (i.e. 90-105 min, no BAM15), average normal and infarcted segments values of VT were 27.1±5.0 and 16.4±2.5, which yielded ΔΨT values of -128.4±5.1 meV and -111.2±2.7 meV in agreement with literature values and with our previous bolus-only measurements [1]. 18F-TPP+ concentration decreased after BAM15 infusion in apical-septal and apical regions, corresponding to the LAD territory, while other segments showed stable tissue concentration during the scan (Figure). Conclusions: Primed constant infusion of 18F-TPP+ can be used to measure VT and ΔΨT with the advantage that subjects need to be scanned during secular equilibrium. The effect of the mitochondrial proton uncoupler, BAM15, demonstrates the sensitivity of the technique to depolarization of the inner mitochondrial membrane. Research Support: P41EB022544 R01HL137230 T32EB013180