DOXORUBICIN-INDUCED CARDIAC NEUROTOXICITY - STUDY WITH IODINE 123-LABELED METAIODOBENZYLGUANIDINE SCINTIGRAPHY

Background. Iodine 123-labeled metaiodobenzylguanidine (I-123-MIBG) ca n 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 I-123-MIBG scintigr aphy and radionuclide ventriculography, Cardiac I-123-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 w ithout doxorubicin, In patients receiving doxorubicin, the H/M ratio w as 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), B y using a HIM ratio of 1.73 as a cutoff point, I-123-MIBG uptake was a bnormal in none of the 23 patients not receiving and 6 of 14 patients receiving doxorubicin therapy (p < 0.001), In 10 patients initially no t receiving doxorubicin, I-123-MIBG scintigraphy was repeated after re ceiving 236 +/- 47 mg/m(2) of doxorubicin. The H/M became abnormal in 3 of 10 patients, whereas the ejection fraction became abnormal in 2 o f 10 patients, Conclusion. I-123-MIBG cardiac uptake decreases in a do xorubicin dose-dependent way, indicating a cardiac adrenergic neurotox ic effect of doxorubicin. This phenomenon appears early and generally before deterioration of the ejection fraction.