Enhancement by tetraphenylborate of technetium-99m-MIBI uptake kinetics and accumulation in cultured chick myocardial cells.
Myocellular uptake and retention of technetium-99m-hexakis (2-methoxyisobutylisonitrile) (Tc-MIBI), a lipophilic cationic myocardial perfusion and viability imaging agent, is dependent on both mitochondrial and plasma-membrane potentials. To test for enhancement of uptake kinetics by lipophilic anions, cultured chick heart cells were exposed to tetraphenylborate (TPB), which produced a concentration-dependent maximal 15-fold increase in Tc-MIBI uptake kinetics (at 3 x 10(-5) M) and enhanced peak accumulation of Tc-MIBI from 165.4 +/- 26.3 to 705.6 +/- 61.3 fmoles/mg protein.nMo (P less than 0.001). Carbonyl cyanide-m-chloro phenylhydrazone (CCCP; 10(-5) M), a mitochondrial uncoupler, rapidly depleted cellular content of Tc-MIBI in the presence of TPB (10(-5) M) from 300.0 +/- 30.0 to 42.5 +/- 1.9 fmole/mg protein.nMo (p less than 0.001). TPB enhanced both uptake rates and net accumulation of Tc-MIBI at all buffer Ko concentrations between 130 mM and 0.54 mM. Tc-MIBI influx rates allowed estimation of plasma-membrane potential as a function of Ko in the presence of valinomycin with a slope of -67 mV/decade (r = -0.99). The results further support a potential-dependent mechanism for cell uptake of Tc-MIBI and suggest a rational approach for increasing tissue extraction fraction in vivo.
Department of Radiology, Harvard Medical School, Boston, Massachusetts.
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D
Piwnica-Worms
J F
JF
Kronauge
M L
ML
Chiu
D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D006321:Heart / Q000000981:diagnostic imaging*; D009206:Myocardium / Q000378:metabolism; D009570:Nitriles / Q000493:pharmacokinetics; D015609:Organotechnetium Compounds / Q000493:pharmacokinetics; D011877:Radionuclide Imaging; D017256:Technetium Tc 99m Sestamibi; D013775:Tetraphenylborate / Q000494:pharmacology*
D009570:Nitriles; D015609:Organotechnetium Compounds; D013775:Tetraphenylborate; D017256:Technetium Tc 99m Sestamibi