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 by
201Tl, (0.5 to 1.0 mCi) scintigraphy were imaged serially, with simultaneously injected mixture of
99mTc-glucarate and
111In-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 and
111In-antimyosin uptake (
r=0.99,
p<0.0001). Both
99mTc-glucarate (
r=−0.777,
p<0.0001) and
111In-antimyosin (
r=−0.775,
p<0.0001) were inversely related to
201Tl distribution.
Conclusions The near perfect correlation between
99mTc-glucarate and
111In-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.
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