Avidity of technetium 99m glucarate for the necrotic myocardium: In vivo and in vitro assessment

Background  Similar to other^99mTc-based infarct-avid agents,^99mTc-glucarate localizes in myocardial infarcts. Whether severely ischemic viable myocytes sequester^99mTc-glucarate is uncertain. To assess the infarct specificity, in vitro and in vivo studies were performed. Methods and Results  H9C2 embryonic rat cardiocytes cultured under normoxia (N) or hypoxia (H) for 24 hours in 7.5 μCi^99mTc-glucarate were compared with necrotic cardiocytes. Mean H/N ratio (3.0±0.004, mean±SD) was significantly less than that of the necrotic/N ratio (39.9±6.5,p<0.01). Reperfused myocardial infarction (MI) in 4 dogs confirmed by²⁰¹Tl, (0.5 to 1.0 mCi) scintigraphy were imaged serially, with simultaneously injected mixture of^99mTc-glucarate and¹¹¹In-antimyosin Fab. Infarcts were detected scintigraphically within 4 to 10 minutes with^99mTc-glucarate.¹¹¹In-antimyosin required more than 1 hour. Myocardial distribution at 5 hours showed a direct correlation between^99mTc-glucarate and¹¹¹In-antimyosin uptake (r=0.99,p<0.0001). Both^99mTc-glucarate (r=−0.777,p<0.0001) and¹¹¹In-antimyosin (r=−0.775,p<0.0001) were inversely related to²⁰¹Tl distribution. Conclusions  The near perfect correlation between^99mTc-glucarate and¹¹¹In-antimyosin uptake (r=0.99) in reperfused canine MI and the insignificant glucarate uptake by viable cardiocytes in vitro attest to the avidity of^99mTc-glucarate for the necrotic myocardium and favor its use as a specific early marker of myocyte necrosis in acute MI. Supported in part by SBIR grant 1R43-HL54410-01 and Molecular Targeting Technology, Inc.