Effect of metabolic inhibition on technetium-99m-MIBI kinetics in cultured chick myocardial cells

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 K(D) ~ 7 x 10^-5). Metabolic inhibition induced by pre-incubation of cells for 2.5 hr in rotenone (10 μM), iodoacetate (1 mM), or both metabolic inhibitors together reduced 1-min [^99mTc]MIBI uptake to 74.1% ± 8.0% (p < 0.05), 6.2% ± 3.4% (p < 0.01), and 10.1% ± 3.6% of control (p < 0.01), respectively (n = 11-12). Half-maximal inhibitory concentration of iodoacetate was ~ 5 μM. 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 < 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.