title: Effect of mitochondrial viability and metabolism on technetium-99m-sestamibi myocardial retention.
abstract: This study investigated the mechanism of myocardial retention of technetium-99m-sestamibi. 99mTc-sestamibi was injected intravenously into guinea pigs, and the myocardium was homogenized and fractionated by differential centrifugation. More than 90% of myocardial 99mTc-sestamibi was localized within the mitochondrial fraction. Calcium was found to release 99mTc-sestamibi from the mitochondrial fraction, with an IC50 of 2.54 +/- 0.98 mM. This effect was potentiated by NaCl, and inhibited by the mitochondrial calcium channel blocker ruthenium red. In vitro uptake of 99mTc-sestamibi was found to increase from 10.5% +/- 3.0% to 61.2% +/- 0.2% with the addition of 10 mM succinate, indicating that respiration is involved. Since irreversible ischemia results in cellular and mitochondrial calcium "overload" and loss of mitochondrial metabolic function, 99mTc-sestamibi should not be retained in necrotic or irreversibly ischemic myocardium, and could potentially act as a sensitive indicator of myocardial cell viability.
authors.affiliation: Du Pont Merck Pharmaceutical Company, Radiopharmaceutical Division, Billerica, MA 01862.
authors.forename: P
authors.initials: P
authors.lastname: Crane
authors.forename: R
authors.initials: R
authors.lastname: Laliberté
authors.forename: S
authors.initials: S
authors.lastname: Heminway
authors.forename: M
authors.initials: M
authors.lastname: Thoolen
authors.forename: C
authors.initials: C
authors.lastname: Orlandi
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002470:Cell Survival / Q000502:physiology; D006168:Guinea Pigs; D006321:Heart / Q000000981:diagnostic imaging*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging; D015428:Myocardial Reperfusion Injury / Q000000981:diagnostic imaging; D011877:Radionuclide Imaging; D012430:Ruthenium Red / Q000494:pharmacology; D017256:Technetium Tc 99m Sestamibi
chemical_list: D012430:Ruthenium Red; D017256:Technetium Tc 99m Sestamibi; D002118:Calcium