Hiroe M, Ohta Y, Fujita N, Nagata M, Toyozaki T, Kusakabe K, Sekiguchi M, Marumo F
Division of Cardiology, Tokyo Medical and Dental University, Japan.
Circulation. 1992 Dec;86(6):1965-72. doi: 10.1161/01.cir.86.6.1965.
The therapeutic value of doxorubicin (DOX) is limited by its cardiotoxicity, which is dose dependent. To improve the detection of such myocardial damage, this study was designed to determine whether the 111In antimyosin antibody Fab could serve as a marker for cardiotoxicity in treated versus control rats on the basis of comparative morphological and hemodynamic findings.
DOX was administered by intravenous injection to rats at a dose of 3 mg.kg-1.week-1 for 5 weeks. Three weeks after the final injection, an intravenous dose of 111In antimyosin, 740 kBq (20 microCi), was administered, and tissue distribution of the radioisotope (percent kilogram dose per gram) was assessed in 48 hours. Myocardial uptake of radioactivity by both ventricles was more prominent in the DOX-treated rats than in control rats (p < 0.001). The heart-to-blood and heart-to-lung uptake ratios were markedly higher in the treated rats than in controls (p < 0.001). As the severity of the myocardial damage increased, there was a progressive increase in myocardial uptake. There was a strong correlation between the severity of myocardial damage and the ventricular end-diastolic pressure (r = 0.84 and r = 0.83 in the left and right ventricles, respectively). On microscopic immunoautoradiography of the DOX-treated heart, there was a specific immunolocalization of the radiotracer in the injured myocytes but no radioactivity in the control myocytes.
111In antimyosin antibody appears to be a useful immunoradiotracer in detecting cardiac damage induced by DOX administration and in assessing the severity of cardiotoxicity. These data reinforce the clinical observation that myocardial imaging using 111In antimyosin Fab is able to provide information to guide the course of patients receiving DOX treatment.
阿霉素（DOX）的治疗价值因其剂量依赖性心脏毒性而受限。为了改善对此类心肌损伤的检测，本研究旨在根据比较形态学和血流动力学结果，确定铟 - 111抗肌球蛋白抗体Fab是否可作为治疗组与对照组大鼠心脏毒性的标志物。
以3mg·kg⁻¹·周⁻¹的剂量给大鼠静脉注射DOX，持续5周。末次注射后3周，静脉注射740kBq（20微居里）的铟 - 111抗肌球蛋白，48小时后评估放射性同位素的组织分布（每克组织中占每千克剂量的百分比）。与对照大鼠相比，DOX治疗组大鼠的两个心室对放射性的心肌摄取更为显著（p < 0.001）。治疗组大鼠的心脏与血液及心脏与肺的摄取比值明显高于对照组（p < 0.001）。随着心肌损伤严重程度的增加，心肌摄取逐渐增加。心肌损伤严重程度与心室舒张末期压力之间存在强相关性（左心室和右心室的r分别为0.84和0.83）。在DOX治疗心脏的微观免疫放射自显影中，放射性示踪剂在受损心肌细胞中有特异性免疫定位，而对照心肌细胞中无放射性。
铟 - 111抗肌球蛋白抗体似乎是检测DOX给药引起的心脏损伤以及评估心脏毒性严重程度的有用免疫放射性示踪剂。这些数据强化了临床观察结果，即使用铟 - 111抗肌球蛋白Fab进行心肌成像能够为指导接受DOX治疗的患者病程提供信息。
