Uptake and release of two new Tc-99m labeled myocardial blood flow imaging agents in cultured cardiac cells

Abstract

Two new neutral lipophilic ^99mTc labeled molecules, chloro (methyboron (1-)-tris[1,2-cyclohexane-dionedioxime 91-)]-N,N′N″N‴N⁗) (SQ 30217) and Bis [1,2-cyclohexanedione dioximato (1-)-0]-[1,2-cyclohexanedione dioximato (2-)-0] borato (2-N,N′N″N‴N⁗) -chloro Tc (SQ 32014), were studied in cultures of beating myocardial cells of newborn rats. The uptake and release kinetics, the effects of various pH levels of the medium, and the effects of three metabolic inhibitors, i.e, ouabain, cyanide and iodoacetate were assessed. Results show that T_1/2 of uptake were 2 min with both tracers, and T_1/2 of release were 12 and 13 min with SQ 32014 and SQ 30217, respectively. The intra/extracellular tracer concentrations was about 15 times higher with SQ 30217 than with SQ 32014. Intracellular concentration was decreased for both tracers at high pH levels, and was only moderately modified otherwise, including in the presence of the metabolic inhibitors. It is concluded that both tracers present very interesting properties for myocardial blood flow imaging, although a higher contrast should be expected with SQ 30217 than with SQ 32014.