HEXAKIS(CARBOMETHOXYISOPROPYLISONITRILE) TECHNETIUM(I), A NEW MYOCARDIAL PERFUSION IMAGING AGENT - BINDING CHARACTERISTICS IN CULTURED CHICK HEART-CELLS

  • 1 January 1988
    • journal article
    • research article
    • Vol. 29  (1) , 55-61
Abstract
Cellular kinetics and binding characteristics of hexakis(carbomethoxyisopropylisonitrile) technetium (1) (Tc-CPl), a new cationic, highly lipophilic myocardial perfusion imaging agent, were evaluated in chick embryo heart cells grown in monolayer culture. Myocytes showed uptake of Tc-CPl to a plateau level with a half-time (t1/2) of 4.1 .+-. 0.7 min (mean .+-. s.e.m.; n=6); t1/2 appeared independent of extracellular Tc-CPl concentration. Plateau level Tc-CPl uptakes (10-16 to 10 -11 mole Tc-CPl/mg cell protein) were a linear function of extracellular Tc-CPl concentration (range: 10-13M to 10-8M, respectively). Tracer 99mTc-CPl uptake (binding) was not competitively displaced by carrier 99Tc-CPl. Uptake was temperature-sensitive; however, several inhibitors of cationic membrane transport (ouabain, amiloride, bumetanide, and verapamil) showed no significant effect. Extreme alkalinization of external load solution (pHo .apprx. 8.5 (partially inhibited Tc-CPl uptake; however, intracellular pH changes showed no effect. Washout from contractile preparations could be described by a two component system: a fast component (myocytes) with a t1/2 .apprx. 4.5 min and a slow component (fibroblasts) with a t1/2 .apprx. 40 min. Cell fractionation experiments showed most of the activity to be associated with the cell membrane fraction. The data do not demonstrate a specific mechanism for uptake of Tc-CPl; however, results suggest binding to myocytes in a manner proportional to the delivery of the complex to the extracellular spaces. Such properties would be desirable for a myocardial perfusion imaging agent.

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