EFFECT OF METABOLIC INHIBITION ON TECHNETIUM-99M-MIBI KINETICS IN CULTURED CHICK MYOCARDIAL-CELLS

  • 1 April 1990
    • journal article
    • research article
    • Vol. 31  (4) , 464-472
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 99m-Tc-MIBI approached a plateau with a half-time 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 Kp .apprx. 7 .times. 10-5). Metabolic inhibition induced by pre-incubation of cells for 2.5 hr in rotenone (10 .mu.M), 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 .apprx. 5 .mu.M. 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.