Decreased Myocardial Tl-201 Uptake inRats: Early Sign of Doxorubicin InducedMyocardial Damage and the Relation toInflammation

Aim: In the present study, we demonstrated that total cardiac 201Tl uptake changes associated with histological findings in DOX-induced early myocardial injury. Method: Early DOX cardiotoxicity was induced in normal rats by giving 15 mg/kg DOX intraperitoneally. Cardiac uptake studies and the blood sampling for creatine kinase (CK) and lactate dehydrogenase (LDH) assay has been performed on the 3rd (acute phase) and 16th days (subacute phase) after the treatment, respectively. Rats were killed by heart puncture and the hearts removed by dissection at 60 min after the injection of 7.4 MBq 201Tl. The ratio of total cardiac uptake to the injected dose (%ID/g x BW, where ID is injected dose and BW is body weight) was calculated. Result: DOX led to a significant decrease in myocardial uptake of 201Tl in both treatment groups (p<0.05). There was no significant difference in the %ID/g x BW between acute and subacute phases (p>0.05). DOX induced a significant increase in the levels of CK and LDH in serum, indicating its early cardiotoxicity (p=0.01). DOX treatment produced disorganization of myocardial fibers, vacuolation of the cardiac myocytes and myocardial necrosis (p=0.01). These cardiomyocyte injuries were accompanied by increased numbers of mononuclear cells (p<0.05). LDH, CK, cardiyomyopathy and mononuclear cell infiltration scores were not found significantly different between acute and subacute phases (p>0.05). Conclusion: The DOX-induced cardiac injury at early stage can be evaluated by 201Tl and the findings may be associated with the myocardial inflammation. Due to the complicated mechanism of DOX injury, we believe that the development process of cardiac injury and the pathological findings should be taken into consideration in interpreting the radiopharmasotic studies to be conducted for the evaluation of the early and late stage cardiac injuries.