increased myocardial 18 f-fdg uptake as a marker of doxorubicin-induced oxidative stress

Oxidative stress and its interference on myocardial metabolism play a major role in doxorubicin (dxr) cardiotoxic cascade. 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). 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. 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.