Abstract 15356: Serial Evaluation of Chemotherapy-Induced Vascular Toxicity in a Rat Model Using 18 F-FDG PET/CT Imaging

Abstract

Introduction: Cancer treatment with chemotherapeutics can lead to off-target effects on the vasculature. Fluorine-18 ( 18 F)-fluorodeoxyglucose (FDG) PET/CT imaging is standard of care for staging and monitoring of numerous cancers and may offer a tool for assessing vascular toxicity. We hypothesized that PET/CT imaging could quantify changes in chemotherapy-induced arterial inflammation. Thus, we sought to validate PET/CT imaging as a tool for assessing vascular toxicity in a rat model using in vivo imaging and post-mortem analyses. Methods: Male Wistar rats (n = 11 total) were divided into a control group that received twice weekly IV saline (n=5; 1 ml/kg) or a group that received twice weekly IV doxorubicin (n=6; 1 mg/kg) for 2.5 weeks (i.e., 7 mg/kg cumulative dose). Rats underwent 18 F-FDG microPET/CT imaging of the abdominal aorta (AA) at 3 time points (baseline, after 4 mg/kg dosing, and after 7 mg/kg cumulative dose) to quantify serial changes in arterial inflammation, expressed as changes in the maximum standard uptake value (SUV max ). Following terminal imaging, AA tissue was harvested and cut into 3 mm sections for gamma counting of 18 F-FDG uptake, hematoxylin and eosin morphological staining, and immunohistochemistry of macrophage expression. Results: In vivo image analyses demonstrated that 18 F-FDG uptake remained unchanged for the control group during the treatment period, but significantly increased from baseline levels in the doxorubicin-treated group after 4 mg/kg (p=0.0007) and 7 mg/kg (p=0.001) cumulative dosing. In vivo image analyses were confirmed by post-mortem gamma counting of 18 F-FDG uptake in anatomically-matched AA tissue samples. Histological analyses revealed increased levels of macrophage expression in sections with increased 18 F-FDG uptake identified by in vivo and ex vivo analyses. Conclusions: 18 F-FDG PET/CT imaging non-invasively quantifies serial changes in chemotherapy-induced arterial toxicity that are at least partially mediated by increased macrophage activity. Routine assessment of 18 F-FDG uptake on PET/CT imaging studies during cancer treatment could provide a translatable approach for characterizing the time course of vascular toxicity associated with various chemotherapeutics.