[I-123]MIBG is a better early marker of anthracycline cardiotoxicity than [F-18]FDG: a preclinical SPECT/CT and simultaneous PET/MR study

Background During anthracycline treatment of cancer, there is a lack for biomarkers of cardiotoxicity besides the cardiac dysfunction. The objective of the present study was to compare [F-18]FDG and [I-123]MIBG (metaiodobenzylguanidine) in a longitudinal study in a doxorubicin-induced cardiotoxicity rat model. Methods Male Wistar Han rats were intravenously administered 3 times at 10 days' interval with saline or doxorubicin (5 mg/kg). [I-123]MIBG SPECT/CT (single photon emission computed tomography-computed tomography) and simultaneous [F-18]FDG PET (positron emission tomography)/7 Tesla cardiac MR (magnetic resonance) imaging acquisitions were performed at 24 h interval before first doxorubicin / saline injection and every 2 weeks during 6 weeks. At 6 weeks, the heart tissue was collected for histomorphometry measurements. Results At week 4, left ventricle (LV) end-diastolic volume was significantly reduced in the doxorubicin group. At week 6, the decreased LV end-diastolic volume was maintained, and LV end-systolic volume was increased resulting in a significant reduction of LV ejection fraction (47 +/- 6% vs. 70 +/- 3%). At weeks 4 and 6, but not at week 2, myocardial [F-18]FDG uptake was decreased compared with the control group (respectively, 4.2 +/- 0.5%ID/g and 9.2 +/- 0.8%ID/g at week 6). Moreover, [F-18]FDG cardiac uptake correlated with cardiac function impairment. In contrast, from week 2, a significant decrease of myocardial [I-123]MIBG heart to mediastinum ratio was detected in the doxorubicin group and was maintained at weeks 4 and 6 with a 45.6% decrease at week 6. Conclusion This longitudinal study precises that after doxorubicin treatment, cardiac [I-123]MIBG uptake is significantly reduced as early as 2 weeks followed by the decrease of the LV end-diastolic volume and [F-18]FDG uptake at 4 weeks and finally by the increase of LV end-systolic volume and decrease of LV ejection fraction at 6 weeks. Cardiac innervation imaging should thus be considered as an early key feature of anthracycline cardiac toxicity.