Assessment of metabolic patterns and new antitumoral treatment in osteosarcoma xenograft models by [ 18 F]FDG and sodium [ 18 F]fluoride PET

Abstract

Background: Osteosarcoma is the most common malignant bone tumor in children and young adults that produces aberrant osteoid. The aim of this study was to assess the utility of 2-deoxy-2-[18F-] fluoro-D-glucose ([ 18 F] FDG) and sodium [ 18 F] Fluoride (Na [ 18 F] F) PET scans in orthotopic murine models of osteosarcoma to describe the metabolic pattern of the tumors, to detect and diagnose tumors and to evaluate the efficacy of a new treatment based in oncolytic adenoviruses. Methods: Orthotopic osteosarcoma murine models were created by the injection of 143B and 531MII cell lines. [ 18 F]FDG and Na [ 18 F] F PET scans were performed 30 days (143B) and 90 days (531MII) post-injection. The antitumor effect of two doses (10 7 and 10 8 pfu) of the oncolytic adenovirus VCN-01 was evaluated in 531 MII model by [ 18 F] FDG PET studies. [ 18 F] FDG uptake was quantified by SUVmax and Total Lesion Glycolysis (TLG) indexes. For Na [ 18 F] F, the ratio tumor SUVmax/hip SUVmax was calculated. PET findings were confirmed by histopathological techniques. Results: The metabolic pattern of tumors was different between both orthotopic models. All tumors showed [ 18 F] FDG uptake, with a sensitivity and specificity of 100%. The [ 18 F] FDG uptake was significantly higher for the 143B model (p < 0.001). Sensitivity for Na [ 18 F] F was around 70% in both models, with a specificity of 100%. 531MII tumors showed a heterogeneous Na [ 18 F] F uptake, significantly higher than 143B tumors (p < 0.01). Importantly, [ 18 F] FDG and Na [ 18 F] F uptake corresponded to highly cellular or osteoid-rich tumors in the histopathological analysis, respectively. [ 18 F] FDG data confirmed that the oncolytic treatment of 531MII tumors produced a significant reduction in growth even with the 10 7 pfu dose. Conclusions: PET studies demonstrated that the different osteosarcoma xenograft models developed tumors with diverse metabolic patterns that can be described by multitracer PET studies. Since not all tumors produced abundant osteoid, [ 18 F] FDG demonstrated a better sensitivity for tumor detection and was able to quantitatively monitor in vivo response to the oncolytic adenovirus VCN-01.