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Hexakis(Carbomethoxyisopropylisonitrile) Technetium(I), A New Myocardial Perfusion Imaging Agent: Binding Characteristics in Cultured Chick Heart Cells

Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts

Correspondence: For reprints contact: David Piwnica-Worms, MD, PhD, Dept. of Radiology, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115.

ABSTRACT

Cellular kinetics and binding characteristics of hexakis(carbomethoxyisopropylisonitrile) technetium(I) (Tc-CPI), 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-CPI to a plateau level with a half-time (t) of 4.1 ± 0.7 min (mean ± s.e.m.; n = 6); t appeared independent of extracellular Tc-CPI concentration. Plateau level Tc-CPI uptakes (10^–16 to 10^–11 mole Tc-CPI/mg cell protein) were a linear function of extracellular Tc-CPI concentration (range: 10^–13M to 10^–8M, respectively). Tracer ^99mTc-CPI uptake (binding) was not competitively displaced by carrier ⁹⁹Tc-CPI. 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 (pH_o 8.5) partially inhibited Tc-CPI 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 t 4.5 min and a slow component (fibroblasts) with a t 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-CPI; 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.