The present translational study aimed to verify whether serial 18FFDG PET/CT predicts doxorubicin cardiotoxicity. Methods: Fifteen athymic mice were treated intravenously with saline (n = 5) or with 5 or 7.5 mg of doxorubicin per kilogram (n = = each) and underwent dynamic small-animal PET beforehand and afterward to estimate left ventricular (LV) metabolic rate of glucose (MRGlu). Thereafter, we retrospectively identified 69 patients who had been successfully treated with a regimen of doxorubicin, bleomycin, vinblastine, and dacarbazine for Hodgkin disease (HD) and had undergone 4 consecutive18F-FDG PET/CT scans. Volumes of interest were drawn on LV myocardium to quantify mean SUV. All patients were subsequently interviewed by telephone (median follow-up, 30 mo); 36 of them agreed to undergo electrocardiography and transthoracic echocardiography. Results: In mice, LV MRGlu was 17.9 Â± 4.4 nmol â¢ min21 Ã g21 at baseline. Doxorubicin selectively and dose-dependently increased this value in the standard-dose (27.9 Â± 9 nmol Ã min21 Ã g-1, P < 0.05 vs. controls) and high-dose subgroups (37.2 6 7.8 nmol Ã min21 Ã g-1, P < 0.01 vs. controls, P < 0.05 vs. standard-dose). In HD patients, LV SUV showed a progressive increase during doxorubicin treatment that persisted at follow-up. New-onset cardiac abnormalities appeared in 11 of 36 patients (31%). In these subjects, pretherapy LV SUV was markedly lower with respect to the remaining patients (1.53 Â± 0.9 vs. 3.34 Â± 2.54, respectively, P < 0.01). Multivariate analysis confirmed the predictive value of baseline LV SUV for subsequent cardiac abnormalities. Conclusion: Doxorubicin dosedependently increases LV MRGlu, particularly in the presence of low baseline18F-FDG uptake. These results imply that low myocardial18F-FDG uptake before the initiation of doxorubicin chemotherapy in HD patients may predict the development of chemotherapy-induced cardiotoxicity, suggesting that prospective clinical trials are warranted to test this hypothesis.
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|Titolo:||Doxorubicin effect on myocardial metabolism as a prerequisite for subsequent development of cardiac toxicity: A translational18F-FDG PET/CT observation|
|Data di pubblicazione:||2017|
|Appare nelle tipologie:||01.01 - Articolo su rivista|