title: Effect of metabolic inhibition on technetium-99m-MIBI kinetics in cultured chick myocardial cells.
abstract: Cellular uptake characteristics of hexakis(methoxyisobutylisonitrile)technetium(I) ([99mTc]MIBI), a myocardial perfusion imaging agent, were evaluated in cultured chick embryo heart cells. Myocyte net uptake of 99mTc-MIBI approached a plateau with a half-time of 9.3 +/- 1.5 min (mean +/- s.e.m.; n = 10). Tracer [99mTc]MIBI showed apparent competitive displacement by carrier [99Tc]MIBI at relatively high molar ratios ([99mTc]MIBI/[99Tc]MIBI) indicating a low affinity cellular retention process (apparent KD approximately 7 x 10(-5)). Metabolic inhibition induced by pre-incubation of cells for 2.5 hr in rotenone (10 microM), iodoacetate (1 mM), or both metabolic inhibitors together reduced 1-min [99mTc] MIBI uptake to 74.1% +/- 8.0% (p less than 0.05), 6.2% +/- 3.4% (p less than 0.01), and 10.1% +/- 3.6% of control (p less than 0.01), respectively (n = 11-12). Half-maximal inhibitory concentration of iodoacetate was approximately 5 microM. Iodoacetate inhibition of [99mTc]MIBI uptake kinetics was time-dependent; no significant effect on [99mTc]MIBI uptake was seen during the first 60 min of metabolic inhibition despite significant depletion of ATP content determined on the same preparations (control ATP: 40.2 nmoles/mg protein versus iodoacetate incubation: 2.8 nmoles/mg protein; p less than 0.01). However, prolonged metabolic blockade did eventually depress 1-min [99mTc]MIBI uptake. These data indicate that a late component of myocardial cell injury can depress [99mTc]MIBI cellular uptake.
authors.affiliation: Departments of Radiology, Brigham and Women's Hospital, Harvard, Medical School, Boston, Massachusetts.
authors.forename: D
authors.initials: D
authors.lastname: Piwnica-Worms
authors.forename: J F
authors.initials: JF
authors.lastname: Kronauge
authors.forename: L
authors.initials: L
authors.lastname: Delmon
authors.forename: B L
authors.initials: BL
authors.lastname: Holman
authors.forename: J D
authors.initials: JD
authors.lastname: Marsh
authors.forename: A G
authors.initials: AG
authors.lastname: Jones
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D003287:Contrast Media; D006207:Half-Life; D006321:Heart / Q000000981:diagnostic imaging* / Q000196:embryology; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D009206:Myocardium / Q000378:metabolism; D009570:Nitriles / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D015609:Organotechnetium Compounds / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D012402:Rotenone / Q000494:pharmacology; D017256:Technetium Tc 99m Sestamibi
chemical_list: D003287:Contrast Media; D007461:Iodoacetates; D009570:Nitriles; D015609:Organotechnetium Compounds; D012402:Rotenone; D017256:Technetium Tc 99m Sestamibi; D019807:Iodoacetic Acid