TY - JOUR
T1 - Doxorubicin effect on myocardial metabolism as a prerequisite for subsequent development of cardiac toxicity
T2 - A translational 18F-FDG PET/CT observation
AU - Bauckneht, Matteo
AU - Ferrarazzo, Giulia
AU - Fiz, Francesco
AU - Morbelli, Silvia
AU - Sarocchi, Matteo
AU - Pastorino, Fabio
AU - Ghidella, Alberto
AU - Pomposelli, Elena
AU - Miglino, Maurizio
AU - Ameri, Pietro
AU - Emionite, Laura
AU - Ticconi, Flavia
AU - Arboscello, Eleonora
AU - Buschiazzo, Ambra
AU - Massimelli, Elena Augusta
AU - Fiordoro, Salvatore
AU - Borra, Anna
AU - Cossu, Vanessa
AU - Bozzano, Annalisa
AU - Ibatici, Adalberto
AU - Ponzoni, Mirco
AU - Spallarossa, Paolo
AU - Gallamini, Andrea
AU - Bruzzi, Paolo
AU - Sambuceti, Gianmario
AU - Marini, Cecilia
PY - 2017/10/1
Y1 - 2017/10/1
N2 - 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 consecutive 18F-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 ± 4.4 nmol • min21 × g21 at baseline. Doxorubicin selectively and dose-dependently increased this value in the standard-dose (27.9 ± 9 nmol × min21 × g-1, P < 0.05 vs. controls) and high-dose subgroups (37.2 6 7.8 nmol × min21 × 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 ± 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 dosedependently increases LV MRGlu, particularly in the presence of low baseline 18F-FDG uptake. These results imply that low myocardial 18F-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.
AB - 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 consecutive 18F-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 ± 4.4 nmol • min21 × g21 at baseline. Doxorubicin selectively and dose-dependently increased this value in the standard-dose (27.9 ± 9 nmol × min21 × g-1, P < 0.05 vs. controls) and high-dose subgroups (37.2 6 7.8 nmol × min21 × 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 ± 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 dosedependently increases LV MRGlu, particularly in the presence of low baseline 18F-FDG uptake. These results imply that low myocardial 18F-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.
KW - Doxorubicin
KW - FDG PET/CT
KW - Myocardial metabolism
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U2 - 10.2967/jnumed.117.191122
DO - 10.2967/jnumed.117.191122
M3 - Article
AN - SCOPUS:85030870986
VL - 58
SP - 1638
EP - 1645
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
SN - 0161-5505
IS - 10
ER -