Study summary · research use only
In-vivo Imaging of Mitochondrial Depolarization of Myocardium With Positron Emission Tomography and a Proton Gradient Uncoupler
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This pig study used positron emission tomography (PET) with the tracer 18F-labeled tetraphenylphosphonium (18F-TPP+) to examine transient changes in tissue membrane potential in myocardium following administration of the proton gradient uncoupler BAM15. Preliminary dose-response experiments in two pigs determined the BAM15 infusate concentration needed to perturb 18F-TPP+ concentration; in two additional pigs, an intravenous bolus plus infusion of 18F-TPP+ was given to reach secular equilibrium, followed by intracoronary BAM15 infusion. The authors report that intracoronary BAM15 infusion produced a clear decrease in 18F-TPP+ concentration that then recovered, that a second infusion produced a similar reduction, and that a maximum depolarization of 10 mV was observed, supporting that 18F-TPP+ PET is sensitive to temporal changes in mitochondrial membrane potential.
Abstract
We recently reported a method using positron emission tomography (PET) and the tracer 18F-labeled tetraphenylphosphonium (18F-TPP+) for mapping the tissue (i.e., cellular plus mitochondrial) membrane potential (ΔΨT) in the myocardium. The purpose of this work is to provide additional experimental evidence that our methods can be used to observe transient changes in the volume of distribution for 18F-TPP+ and mitochondrial membrane potential (ΔΨm). We tested these hypotheses by measuring decreases of 18F-TPP+ concentration elicited when a proton gradient uncoupler, BAM15, is administered by intracoronary infusion during PET scanning. BAM15 is the first proton gradient uncoupler shown to affect the mitochondrial membrane without affecting the cellular membrane potential. Preliminary dose response experiments were conducted in two pigs to determine the concentration of BAM15 infusate necessary to perturb the 18F-TPP+ concentration. More definitive experiments were performed in two additional pigs, in which we administered an intravenous bolus plus infusion of 18F-TPP+ to reach secular equilibrium followed by an intracoronary infusion of BAM15. Intracoronary BAM15 infusion led to a clear decrease in 18F-TPP+ concentration, falling to a lower level, and then recovering. A second BAM15 infusion reduced the 18F-TPP+ level in a similar fashion. We observed a maximum depolarization of 10 mV as a result of the BAM15 infusion. This work provides evidence that the total membrane potential measured with 18F-TPP+ PET is sensitive to temporal changes in mitochondrial membrane potential.
pepmg summarizes the peer-reviewed literature and links to every source — it sells nothing, ships nothing, and gives no medical, dosing, or human-use guidance. Don't just trust this summary: follow the citation to its source and read it yourself. Research use only.