Metaiodobenzylguanidine: Evaluation of its potential as a tracer for monitoring doxorubicin cardiomyopathy

We evaluated alterations in cardiac adrenergic neuron activity and progression of left ventricular dysfunction in comparison with the severity of structural changes using a rat model of adriamycin cardiomyopathy. Rats were treated with adriamycin (2 mg/kg s.c. once a week) for 6, 7, 8 and 9 wk. Accumulation of ¹²⁵I-metaiodobenzylguanidine (MIBG) 4 hr after intravenous administration was determined and left ventricular ejection fraction (LVEF) was calculated from gated blood-pool images. H and E and Masson-Trichrome stained specimens of the myocardium were examined by light microscopy. Histopathologic examination demonstrated dose-dependent myocyte damage, although there were no differences between the 8-wk and 9-wk groups. LVEF did not differ between controls and the 6-wk group (81.3% ± 5.5% versus 82.1% ± 4.8%, p = ns). LVEF began to decrease slightly in the 7-wk group (75.0% ± 5.7%, p < 0.05) and showed a remarkable decrease in the 8-wk group (53.7% ± 2.6%, p < 0.001). In the 9-wk group, LVEF diminished to 47.9% ± 3.1% (p < 0.001), accompanied by massive pleural effusions and ascites. MIBG accumulation in the heart (%ID/heart) significantly and progressively diminished; 1.42% ± 0.15% in the 6-wk group, 1.06% ± 0.16% in the 7-wk group, 0.77% ± 0.13% in the 8-wk group and 0.34% ± 0.11% in the 9-wk group, respectively p < 0.001, compared to controls (1.99% ± 0.30%). These results demonstrate that MIBG accumulation in the heart showed a greater and more linear dose-dependent decrease than LVEF. Furthermore, MIBG uptake was significantly reduced in the 6-wk group where only mild myocyte damage (isolated vacuolation or myofibrillar loss) was observed. Thus, MIBG may be a sensitive biochemical marker of adriamycin cardiomyopathy.