Indium 111 antimyosin and Tc-99m glucaric acid for noninvasive identification of oncotic and apoptotic myocardial necrosis.
BACKGROUND
Noninvasive imaging techniques would be highly desirable to differentiate oncotic from apoptotic cell death. Indium 111 antimyosin and technetium 99m glucaric acid were used to assess whether apoptotic and oncotic myocardial cell death can be differentiated.


RESULTS
Cultured H9C2 rat embryonic cardiocytes and CD1 rats were treated with doxorubicin to induce myocardial apoptosis. Acute myocardial oncosis was induced by heat or subcutaneous isoproterenol administration. Scanning electron microscopy, DNA laddering, TUNEL staining, In-111 antimyosin antibody, and Tc-99m glucaric acid were used to demonstrate in vitro and in vivo doxorubicin-induced apoptosis or isoproterenol-induced myocardial oncosis. Scanning electron microscopy, DNA laddering, and TUNEL staining of H9C2 cardiocytes treated with doxorubicin all showed cell death by apoptosis. Rat hearts treated with doxorubicin (10 and 20 mg/kg) were DNA ladder-positive and localized significantly greater In-111 antimyosin antibody (mean +/- SD, 0.1942 +/- 0.0150 percent injected dose per gram [%ID/g] and 0.1825 +/- 0.0238 %ID/g, respectively) than normal hearts (0.1154 +/- 0.0270 %ID/g, P <.05). No increase in myocardial Tc-99m glucaric acid activity was observed in rat hearts after 6, 12, and 24 hours of doxorubicin injection (0.0311 +/- 0.0066 %ID/g, 0.0356 +/- 0.007 %ID/g, and 0.0368 +/- 0.0047 %ID/g, respectively; control hearts, 0.0352 +/- 0.0099 %ID/g; P = not significant). Tc-99m glucaric acid uptake was significantly greater in isoproterenol-induced oncotic hearts (0.1256 +/- 0.1023 %ID/g) than in controls (P <.0001).


CONCLUSIONS
Tc-99m glucaric acid is avid only for the oncotic myocardium. Antimyosin, on the other hand, is positive for both oncotic and apoptotic myocardium.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D017209:Apoptosis; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D003937:Diagnosis, Differential; D004317:Doxorubicin / Q000494:pharmacology; D006321:Heart / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D007545:Isoproterenol / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009336:Necrosis; D016719:Radioimmunodetection / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D013667:Technetium / Q000493:pharmacokinetics
D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D019275:Radiopharmaceuticals; D013667:Technetium; D004317:Doxorubicin; D004247:DNA; D007545:Isoproterenol