The development of 99mTc-analog of Cu-DTS as an agent for imaging hypoxia

Works on dithiosemicarbazone (DTS) derivatives radiolabeled with divalent Cu (Cu-62, Cu-64) indicate its potentiality as an ischemic tissue detecting agent. Development of analogous derivatives labeled with the more accessible technetium-99m (Tc) is most desirable. Various synthesized DTS derivatives are radiolabeled with a novel approach, using a macromolecular Sn(II)-complex under an anaerobic condition at pH 3.4-4.5 and stabilization by ascorbate solution at pH 6.7-7.0. Characterization of Tc-DTS derivatives done by various analytical methods (TLC, HPLC, EP, PC) and by in vivo studies in normal mice and in rats myocardial LAD (left anterior descent coronary artery) occlusion model. Among tested DTS, only Tc-ATSE, Tc-ATSM and Tc-ATSM(2) showed distinctive characteristics, with the latter presenting high myocardium uptake in regions of ischemia in LAD rat myocardium model. Potentiality of the Cu-DTS mimetic agent, Tc-ATSM(2) as an ischemia-damaged myocardium agent is discussed. NUCL MED BIOL 27;4:391-399, 2000. (C) 2000 Elsevier Science Inc. All rights reserved.