The development of (99m)Tc-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.
Kyoto University, Faculty of Pharmaceutical Sciences, Kyoto, Japan. shkazuko@pharm.kyoto-u.ac.jp
K
K
Horiuchi
T
T
Tsukamoto
M
M
Saito
M
M
Nakayama
Y
Y
Fujibayashi
H
H
Saji
D000818:Animals; D003301:Copper Radioisotopes; D006863:Hydrogen-Ion Concentration; D000860:Hypoxia / Q000000981:diagnostic imaging*; D008297:Male; D051379:Mice; D017202:Myocardial Ischemia / Q000000981:diagnostic imaging*; D011877:Radionuclide Imaging; D051381:Rats; D017208:Rats, Wistar; D013667:Technetium; D013882:Thiosemicarbazones / Q000378:metabolism*; D014018:Tissue Distribution
D003301:Copper Radioisotopes; D013882:Thiosemicarbazones; C015848:dithiosemicarbazone; D013667:Technetium