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Bauckneht M, Pastorino F, Castellani P, et al. Increased myocardial . J Nucl Cardiol. 2019;27(6):2183-2194doi: 10.1007/s12350-019-01618-x.
Bauckneht, M., Pastorino, F., Castellani, P., Cossu, V., Orengo, A. M., Piccioli, P., Emionite, L., Capitanio, S., Yosifov, N., Bruno, S., Lazzarini, E., Ponzoni, M., Ameri, P., Rubartelli, A., Ravera, S., Morbelli, S., Sambuceti, G., & Marini, C. (2020). Increased myocardial . Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology, 27(6), 2183-2194. https://doi.org/10.1007/s12350-019-01618-x
Bauckneht, Matteo, et al. "Increased myocardial ." Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology vol. 27,6 (2020): 2183-2194. doi: https://doi.org/10.1007/s12350-019-01618-x
Bauckneht M, Pastorino F, Castellani P, Cossu V, Orengo AM, Piccioli P, Emionite L, Capitanio S, Yosifov N, Bruno S, Lazzarini E, Ponzoni M, Ameri P, Rubartelli A, Ravera S, Morbelli S, Sambuceti G, Marini C. Increased myocardial . J Nucl Cardiol. 2020 Dec;27(6):2183-2194. doi: 10.1007/s12350-019-01618-x. Epub 2019 Feb 08. PMID: 30737636.
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J Nucl Cardiol. 2020 Dec;27(6):2183-2194. doi: 10.1007/s12350-019-01618-x. Epub 2019 Feb 08.

Increased myocardial .

Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology

Matteo Bauckneht, Fabio Pastorino, Patrizia Castellani, Vanessa Cossu, Anna Maria Orengo, Patrizia Piccioli, Laura Emionite, Selene Capitanio, Nikola Yosifov, Silvia Bruno, Edoardo Lazzarini, Mirco Ponzoni, Pietro Ameri, Anna Rubartelli, Silvia Ravera, Silvia Morbelli, Gianmario Sambuceti, Cecilia Marini

Affiliations

  1. Nuclear Medicine, IRCCS Ospedale Policlinico San Martino, Genoa, Italy. [email protected].
  2. Nuclear Medicine, Department of Health Sciences (DISSAL), University of Genoa, Largo R. Benzi 10, 16132, Genoa, Italy. [email protected].
  3. Laboratory of Experimental Therapy in Oncology, Istituto Giannina Gaslini, Genoa, Italy.
  4. Cell Biology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
  5. Nuclear Medicine, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
  6. Animal Facility, IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
  7. Department of Experimental Medicine, University of Genoa, Genoa, Italy.
  8. Cardiovascular Disease Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy.
  9. Department of Internal Medicine & Centre of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
  10. Nuclear Medicine, Department of Health Sciences (DISSAL), University of Genoa, Largo R. Benzi 10, 16132, Genoa, Italy.
  11. CNR Institute of Molecular Bioimaging and Physiology, Milan, Italy.

PMID: 30737636 DOI: 10.1007/s12350-019-01618-x

Abstract

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.

Keywords: Doxorubicin; Positron emission tomography; cardiotoxicity; myocardial metabolism; oxidative stress, hexose-6-phosphate-dehydrogenase

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