Measurement of (18)F-FDG PET tumor heterogeneity improves early assessment of response to bevacizumab compared with the standard size and uptake metrics in a colorectal cancer model

PURPOSE: Treatment of metastatic colorectal cancer frequently includes antiangiogenic agents such as bevacizumab. Size measurements are inadequate to assess treatment response to these agents, and newer response assessment criteria are needed. We aimed to evaluate (18)F-FDG PET-derived texture parameters in a preclinical colorectal cancer model as alternative metrics of response to treatment with bevacizumab. MATERIALS AND METHODS: Fourteen CD1 athymic mice injected in the flank with 5×106 LS174T cells (human colorectal carcinoma) were either untreated controls (n=7) or bevacizumab treated (n=7). After 2 weeks, mice underwent (18)F-FDG PET/CT. Calliper-measured tumor growth (Δ(vol)) and final tumor volume (Vol(cal)), (18)F-FDG PET metabolically active volume (Vol(met)), mean metabolism (Met(mean)), and maximum metabolism (Met(max)) were measured. Twenty-four texture features were compared between treated and untreated mice. Immunohistochemical mean tumor vascular density was estimated by anti-CD-34 staining after tumor resection. RESULTS: Treated mice had significantly lower tumor vascular density (P=0.032), confirming the antiangiogenic therapeutic effect of bevacizumab. None of the conventional measures were different between the two groups: Δ(vol) (P=0.9), Vol(cal) (P=0.7), Vol(met) (P=0.28), Met(max) (P=0.7), or Met(mean) (P=0.32). One texture parameter, GLSZM-SZV (visually indicating that the (18)F-FDG PET images of treated mice comprise uniformly sized clusters of different activity) had significantly different means between the two groups of mice (P=0.001). CONCLUSION: (18)F-FDG PET derived texture parameters, particularly GLSZM-SZV, may be valid biomarkers of tumor response to treatment with bevacizumab, before change in volume.