OBJECTIVES: This study tested the hypothesis that 4-[(18)F]fluorophenyltriphenylphosphonium ((18)F-TPP) is useful for in vivo positron emission tomography (PET) measurement of mitochondrial membrane potential (ΔΨm). Its utility as a blood flow tracer also was evaluated. BACKGROUND: Tetraphenylphosphonium is useful for in vitro measurement of ΔΨm. In vivo measurement of ΔΨm has potential value in the assessment of heart failure pathophysiology and therapy as well as assessment of myocardial viability and so may be a very useful clinical tool. METHODS: Anesthetized swine (N = 6) with a balloon catheter in the left anterior descending coronary artery were studied. Microsphere measurements of myocardial blood flow (MBF) were made after balloon inflation (baseline) and ∼10 min after intravenous administration of adenosine and phenylephrine after which ∼10 mCi (18)F-TPP was injected intravenously and dynamic PET data acquisition obtained for 30 min. After the swine were killed, the hearts were sectioned for microsphere measurement of MBF and (18)F-TPP measured by well counter in these same samples. PET images provided whole blood and myocardial (18)F-TPP concentration for determination of ΔΨm by the Nernst equation, corrected for nonspecific (18)F-TPP binding. Microsphere MBF, absolute (ml/min/g) and relative, was compared with PET data (standard uptake value and K1). RESULTS: Nonspecific binding of (18)F-TPP overestimated ΔΨm measured by -37 ± 4 mV (mean ± SD). Normal zone ΔΨm of ex vivo samples (-91 ± 11 mV; N = 52; sample weight, 1.07 ± 0.18 g) correlated strongly (R(2)= 0.93) with normal zone by PET (-81 ± 13 mV). Both ex vivo and PET normal zone ΔΨm, although somewhat lower, compared well with that reported for tritium labeled triphenylphosphonium in normal working Langendorff rat heart (-100 mV). Although the relative MBF by (18)F-TPP correlated strongly with relative microsphere MBF (R(2)= 0.83), there was no correlation between absolute MBF by (18)F-TPP and microsphere MBF. CONCLUSIONS: (18)F-TPP is a promising tracer for noninvasive PET measurement of ΔΨm in living subjects. It is useful as well for assessment of relative but not absolute MBF.
OBJECTIVES: This study tested the hypothesis that 4-[(18)F]fluorophenyltriphenylphosphonium ((18)F-TPP) is useful for in vivo positron emission tomography (PET) measurement of mitochondrial membrane potential (ΔΨm). Its utility as a blood flow tracer also was evaluated. BACKGROUND:Tetraphenylphosphonium is useful for in vitro measurement of ΔΨm. In vivo measurement of ΔΨm has potential value in the assessment of heart failure pathophysiology and therapy as well as assessment of myocardial viability and so may be a very useful clinical tool. METHODS: Anesthetized swine (N = 6) with a balloon catheter in the left anterior descending coronary artery were studied. Microsphere measurements of myocardial blood flow (MBF) were made after balloon inflation (baseline) and ∼10 min after intravenous administration of adenosine and phenylephrine after which ∼10 mCi (18)F-TPP was injected intravenously and dynamic PET data acquisition obtained for 30 min. After the swine were killed, the hearts were sectioned for microsphere measurement of MBF and (18)F-TPP measured by well counter in these same samples. PET images provided whole blood and myocardial (18)F-TPP concentration for determination of ΔΨm by the Nernst equation, corrected for nonspecific (18)F-TPP binding. Microsphere MBF, absolute (ml/min/g) and relative, was compared with PET data (standard uptake value and K1). RESULTS: Nonspecific binding of (18)F-TPP overestimated ΔΨm measured by -37 ± 4 mV (mean ± SD). Normal zone ΔΨm of ex vivo samples (-91 ± 11 mV; N = 52; sample weight, 1.07 ± 0.18 g) correlated strongly (R(2)= 0.93) with normal zone by PET (-81 ± 13 mV). Both ex vivo and PET normal zone ΔΨm, although somewhat lower, compared well with that reported for tritium labeled triphenylphosphonium in normal working Langendorffrat heart (-100 mV). Although the relative MBF by (18)F-TPP correlated strongly with relative microsphere MBF (R(2)= 0.83), there was no correlation between absolute MBF by (18)F-TPP and microsphere MBF. CONCLUSIONS: (18)F-TPP is a promising tracer for noninvasive PET measurement of ΔΨm in living subjects. It is useful as well for assessment of relative but not absolute MBF.
Authors: Ji Who Kim; Seongho Seo; Hyeon Sik Kim; Dong-Yeon Kim; Ho-Young Lee; Keon Wook Kang; Dong Soo Lee; Hee-Seung Bom; Jung-Joon Min; Jae Sung Lee Journal: Ann Nucl Med Date: 2017-04-25 Impact factor: 2.668
Authors: Anna A Rybczynska; Hendrikus H Boersma; Steven de Jong; Jourik A Gietema; Walter Noordzij; Rudi A J O Dierckx; Philip H Elsinga; Aren van Waarde Journal: Med Res Rev Date: 2018-03-12 Impact factor: 12.944
Authors: Matthieu Pelletier-Galarneau; Yoann Petibon; Chao Ma; Paul Han; Sally Ji Who Kim; Felicitas J Detmer; Daniel Yokell; Nicolas Guehl; Marc Normandin; Georges El Fakhri; Nathaniel M Alpert Journal: Eur J Nucl Med Mol Imaging Date: 2020-07-27 Impact factor: 9.236
Authors: Nathaniel M Alpert; Nicolas Guehl; Leon Ptaszek; Matthieu Pelletier-Galarneau; Jeremy Ruskin; Moussa C Mansour; Dustin Wooten; Chao Ma; Kazue Takahashi; Yun Zhou; Timothy M Shoup; Marc D Normandin; Georges El Fakhri Journal: PLoS One Date: 2018-01-16 Impact factor: 3.240