The present translational study aimed to verify whether serial 18F-fluoro-deoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT), predicts doxorubicin cardiotoxicity. Methods: Fifteen athymic mice were treated with intravenous administration of saline (n = 5), doxorubicin 5 mg/Kg (n = 5) or doxorubicin 7.5 mg/Kg (n = 5) and submitted to dynamic microPET scan to estimate left ventricular glucose consumption (LV-MRGlu) before and after chemotherapy. Thereafter, we retrospectively identified 69 patients successfully treated with Adriamycin, Bleomycin, Vinblastine, and Dacarbazine (ABVD) regimen for Hodgkin's Disease (HD) and submitted to four consecutive FDG-PET/CT scans. Volumes of interest were drawn on LV myocardium to quantify mean standardized uptake value (LV-SUV). All patients were subsequently interviewed by telephone (median follow-up: 30 months); 36 of them accepted to undergo electrocardiogram and transthoracic echocardiography. Results: In mice LV-MRGlu was 17.9±4.4 nMol x min-1 x g-1 at baseline. doxorubicin selectively and dose-dependently increased this value in the standard-dose (27.9±9 nMol x min-1 x g-1, p<0.05 vs. controls) and in the high-dose subgroup (37.2±7.8 nMol x min-1 x 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 11/36 (31%) patients. In these subjects, pre-therapy LV-SUV was markedly lower with respect to the remaining ones (1.53±0.9 vs 3.34±2.54, respectively, p<0.01. Multivariate analysis confirmed the predictive value of baseline LV-SUV for subsequent cardiac abnormalities. Conclusion: Doxorubicin dose-dependently increases LV-MRGlu, particularly in presence of low baseline FDG uptake. These results imply that low myocardial FDG uptake prior to 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.
Doxorubicin effect on myocardial metabolism as a pre-requisite for subsequent development of cardiac toxicity: a translational 18F-FDG PET/CT observation.
Cecilia Marini
2017
Abstract
The present translational study aimed to verify whether serial 18F-fluoro-deoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT), predicts doxorubicin cardiotoxicity. Methods: Fifteen athymic mice were treated with intravenous administration of saline (n = 5), doxorubicin 5 mg/Kg (n = 5) or doxorubicin 7.5 mg/Kg (n = 5) and submitted to dynamic microPET scan to estimate left ventricular glucose consumption (LV-MRGlu) before and after chemotherapy. Thereafter, we retrospectively identified 69 patients successfully treated with Adriamycin, Bleomycin, Vinblastine, and Dacarbazine (ABVD) regimen for Hodgkin's Disease (HD) and submitted to four consecutive FDG-PET/CT scans. Volumes of interest were drawn on LV myocardium to quantify mean standardized uptake value (LV-SUV). All patients were subsequently interviewed by telephone (median follow-up: 30 months); 36 of them accepted to undergo electrocardiogram and transthoracic echocardiography. Results: In mice LV-MRGlu was 17.9±4.4 nMol x min-1 x g-1 at baseline. doxorubicin selectively and dose-dependently increased this value in the standard-dose (27.9±9 nMol x min-1 x g-1, p<0.05 vs. controls) and in the high-dose subgroup (37.2±7.8 nMol x min-1 x 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 11/36 (31%) patients. In these subjects, pre-therapy LV-SUV was markedly lower with respect to the remaining ones (1.53±0.9 vs 3.34±2.54, respectively, p<0.01. Multivariate analysis confirmed the predictive value of baseline LV-SUV for subsequent cardiac abnormalities. Conclusion: Doxorubicin dose-dependently increases LV-MRGlu, particularly in presence of low baseline FDG uptake. These results imply that low myocardial FDG uptake prior to 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
