Doxorubicin-induced cardiac neurotoxicity: study with iodine 123-labeled metaiodobenzylguanidine scintigraphy.

BACKGROUND

Iodine 123-labeled metaiodobenzylguanidine (123I-MIBG) can be used to generate a scintigraphic image of the adrenergic nervous innervation of the heart.

METHODS AND RESULTS

To test the hypothesis that doxorubicin may lead to damage of cardiac neurons, we examined 37 patients with various malignant neoplasms, 14 of whom were on therapy with doxorubicin. All patients were examined with 123I-MIBG scintigraphy and radionuclide ventriculography. Cardiac 123I-MIBG uptake was assessed by means of a heart to mediastinum activity ratio (H/M). Left ventricular ejection fraction was not different in patients with or without doxorubicin. In patients receiving doxorubicin, the H/M ratio was significantly lower (1.73 +/- 0.25 vs 2.13 +/- 0.25, p < 0.001) and correlated with doxorubicin cumulative dose (r = -0.51, p < 0.001). By using a H/M ratio of 1.73 as a cutoff point, 123I-MIBG uptake was abnormal in none of the 23 patients not receiving and 6 of 14 patients receiving doxorubicin therapy (p < 0.001). In 10 patients initially not receiving doxorubicin, 123I-MIBG scintigraphy was repeated after receiving 236 +/- 47 mg/m2 of doxorubicin. The H/M became abnormal in 3 of 10 patients, whereas the ejection fraction became abnormal in 2 of 10 patients.

CONCLUSION

123I-MIBG cardiac uptake decreases in a doxorubicin dose-dependent way, indicating a cardiac adrenergic neurotoxic effect of doxorubicin. This phenomenon appears early and generally before deterioration of the ejection fraction.