TY - JOUR
T1 - Increased myocardial
18
F-FDG uptake as a marker of Doxorubicin-induced oxidative stress
AU - Bauckneht, Matteo
AU - Pastorino, Fabio
AU - Castellani, Patrizia
AU - Cossu, Vanessa
AU - Orengo, Anna Maria
AU - Piccioli, Patrizia
AU - Emionite, Laura
AU - Capitanio, Selene
AU - Yosifov, Nikola
AU - Bruno, Silvia
AU - Lazzarini, Edoardo
AU - Ponzoni, Mirco
AU - Ameri, Pietro
AU - Rubartelli, Anna
AU - Ravera, Silvia
AU - Morbelli, Silvia
AU - Sambuceti, Gianmario
AU - Marini, Cecilia
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Background: Oxidative stress and its interference on myocardial metabolism play a major role in Doxorubicin (DXR) cardiotoxic cascade. Methods: Mice models of neuroblastoma (NB) were treated with 5 mg DXR/kg, either free (Free-DXR) or encapsulated in untargeted (SL[DXR]) or in NB-targeting Stealth Liposomes (pep-SL[DXR] and TP-pep-SL[DXR]). Control mice received saline. FDG-PET was performed at baseline (PET1) and 7 days after therapy (PET2). At PET2 Troponin-I and NT-proBNP were assessed. Explanted hearts underwent biochemical, histological, and immunohistochemical analyses. Finally, FDG uptake and glucose consumption were simultaneously measured in cultured H9c2 in the presence/absence of Free-DXR (1 μM). Results: Free-DXR significantly enhanced the myocardial oxidative stress. Myocardial-SUV remained relatively stable in controls and mice treated with liposomal formulations, while it significantly increased at PET2 with respect to baseline in Free-DXR. At this timepoint, myocardial-SUV was directly correlated with both myocardial redox stress and hexose-6-phosphate-dehydrogenase (H6PD) enzymatic activity, which selectively sustain cellular anti-oxidant mechanisms. Intriguingly, in vitro, Free-DXR selectively increased FDG extraction fraction without altering the corresponding value for glucose. Conclusion: The direct correlation between cardiac FDG uptake and oxidative stress indexes supports the potential role of FDG-PET as an early biomarker of DXR oxidative damage.
AB - Background: Oxidative stress and its interference on myocardial metabolism play a major role in Doxorubicin (DXR) cardiotoxic cascade. Methods: Mice models of neuroblastoma (NB) were treated with 5 mg DXR/kg, either free (Free-DXR) or encapsulated in untargeted (SL[DXR]) or in NB-targeting Stealth Liposomes (pep-SL[DXR] and TP-pep-SL[DXR]). Control mice received saline. FDG-PET was performed at baseline (PET1) and 7 days after therapy (PET2). At PET2 Troponin-I and NT-proBNP were assessed. Explanted hearts underwent biochemical, histological, and immunohistochemical analyses. Finally, FDG uptake and glucose consumption were simultaneously measured in cultured H9c2 in the presence/absence of Free-DXR (1 μM). Results: Free-DXR significantly enhanced the myocardial oxidative stress. Myocardial-SUV remained relatively stable in controls and mice treated with liposomal formulations, while it significantly increased at PET2 with respect to baseline in Free-DXR. At this timepoint, myocardial-SUV was directly correlated with both myocardial redox stress and hexose-6-phosphate-dehydrogenase (H6PD) enzymatic activity, which selectively sustain cellular anti-oxidant mechanisms. Intriguingly, in vitro, Free-DXR selectively increased FDG extraction fraction without altering the corresponding value for glucose. Conclusion: The direct correlation between cardiac FDG uptake and oxidative stress indexes supports the potential role of FDG-PET as an early biomarker of DXR oxidative damage.
KW - cardiotoxicity
KW - Doxorubicin
KW - myocardial metabolism
KW - oxidative stress, hexose-6-phosphate-dehydrogenase
KW - Positron emission tomography
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U2 - 10.1007/s12350-019-01618-x
DO - 10.1007/s12350-019-01618-x
M3 - Article
AN - SCOPUS:85061338972
JO - Journal of Nuclear Cardiology
JF - Journal of Nuclear Cardiology
SN - 1071-3581
ER -