In-vivo Imaging of Mitochondrial Depolarization of Myocardium With Positron Emission Tomography and a Proton Gradient Uncoupler
BackgroundWe 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 exper...
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| Format: | Article |
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Frontiers Media S.A.
2020-05-01
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| Series: | Frontiers in Physiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphys.2020.00491/full |
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| author | Nathaniel M. Alpert Matthieu Pelletier-Galarneau Matthieu Pelletier-Galarneau Sally Ji Who Kim Yoann Petibon Tao Sun Karla M. Ramos-Torres Marc D. Normandin Georges El Fakhri |
| author_facet | Nathaniel M. Alpert Matthieu Pelletier-Galarneau Matthieu Pelletier-Galarneau Sally Ji Who Kim Yoann Petibon Tao Sun Karla M. Ramos-Torres Marc D. Normandin Georges El Fakhri |
| author_sort | Nathaniel M. Alpert |
| collection | DOAJ |
| description | BackgroundWe 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).MethodsWe 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.ResultsIntracoronary 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.SummaryThis work provides evidence that the total membrane potential measured with 18F-TPP+ PET is sensitive to temporal changes in mitochondrial membrane potential. |
| first_indexed | 2024-12-10T06:58:21Z |
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| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-10T06:58:21Z |
| publishDate | 2020-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-f75d9d85d221431185f1fd3c04e573e42022-12-22T01:58:23ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2020-05-011110.3389/fphys.2020.00491525684In-vivo Imaging of Mitochondrial Depolarization of Myocardium With Positron Emission Tomography and a Proton Gradient UncouplerNathaniel M. Alpert0Matthieu Pelletier-Galarneau1Matthieu Pelletier-Galarneau2Sally Ji Who Kim3Yoann Petibon4Tao Sun5Karla M. Ramos-Torres6Marc D. Normandin7Georges El Fakhri8Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesGordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesDepartment of Medical Imaging, Montreal Heart Institute, Montreal, QC, CanadaGordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesGordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesGordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesGordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesGordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesGordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United StatesBackgroundWe 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).MethodsWe 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.ResultsIntracoronary 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.SummaryThis work provides evidence that the total membrane potential measured with 18F-TPP+ PET is sensitive to temporal changes in mitochondrial membrane potential.https://www.frontiersin.org/article/10.3389/fphys.2020.00491/fullmitochondrial membrane potentialtissue membrane potentialtetraphenylphosphoniumpositron emission tomographyBAM15 |
| spellingShingle | Nathaniel M. Alpert Matthieu Pelletier-Galarneau Matthieu Pelletier-Galarneau Sally Ji Who Kim Yoann Petibon Tao Sun Karla M. Ramos-Torres Marc D. Normandin Georges El Fakhri In-vivo Imaging of Mitochondrial Depolarization of Myocardium With Positron Emission Tomography and a Proton Gradient Uncoupler Frontiers in Physiology mitochondrial membrane potential tissue membrane potential tetraphenylphosphonium positron emission tomography BAM15 |
| title | In-vivo Imaging of Mitochondrial Depolarization of Myocardium With Positron Emission Tomography and a Proton Gradient Uncoupler |
| title_full | In-vivo Imaging of Mitochondrial Depolarization of Myocardium With Positron Emission Tomography and a Proton Gradient Uncoupler |
| title_fullStr | In-vivo Imaging of Mitochondrial Depolarization of Myocardium With Positron Emission Tomography and a Proton Gradient Uncoupler |
| title_full_unstemmed | In-vivo Imaging of Mitochondrial Depolarization of Myocardium With Positron Emission Tomography and a Proton Gradient Uncoupler |
| title_short | In-vivo Imaging of Mitochondrial Depolarization of Myocardium With Positron Emission Tomography and a Proton Gradient Uncoupler |
| title_sort | in vivo imaging of mitochondrial depolarization of myocardium with positron emission tomography and a proton gradient uncoupler |
| topic | mitochondrial membrane potential tissue membrane potential tetraphenylphosphonium positron emission tomography BAM15 |
| url | https://www.frontiersin.org/article/10.3389/fphys.2020.00491/full |
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