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 ([¹⁸F] FDG) and sodium [¹⁸F] Fluoride (Na [¹⁸F] 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. [¹⁸F]FDG and Na [¹⁸F] F PET scans were performed 30 days (143B) and 90 days (531MII) post-injection. The antitumor effect of two doses (10⁷ and 10⁸ pfu) of the oncolytic adenovirus VCN-01 was evaluated in 531 MII model by [¹⁸F] FDG PET studies. [¹⁸F] FDG uptake was quantified by SUVmax and Total Lesion Glycolysis (TLG) indexes. For Na [¹⁸F] 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 [¹⁸F] FDG uptake, with a sensitivity and specificity of 100%. The [¹⁸F] FDG uptake was significantly higher for the 143B model (p < 0.001). Sensitivity for Na [¹⁸F] F was around 70% in both models, with a specificity of 100%. 531MII tumors showed a heterogeneous Na [¹⁸F] F uptake, significantly higher than 143B tumors (p < 0.01). Importantly, [¹⁸F] FDG and Na [¹⁸F] F uptake corresponded to highly cellular or osteoid-rich tumors in the histopathological analysis, respectively. [¹⁸F] FDG data confirmed that the oncolytic treatment of 531MII tumors produced a significant reduction in growth even with the 10⁷ 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, [¹⁸F] FDG demonstrated a better sensitivity for tumor detection and was able to quantitatively monitor in vivo response to the oncolytic adenovirus VCN-01.

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