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

PurposeTreatment of metastatic colorectal cancer frequently includes anti-angiogenic agents such as bevacizumab. Size measurements are inadequate to assessment treatment response to these agents, and newer response assessment criteria are needed. We aimed to evaluate 18-fluoro-2-deoxyglucose positron emission tomography (18F-FDG PET)-derived texture parameters in a preclinical colorectal cancer model as alternative metrics of response to treatment with bevacizumab. Methods Fourteen CD1 athymic mice injected in the flank with 5 x 106 LS174T cells (human colorectal carcinoma) were either untreated controls (n=7) or bevacizumab treated (n=7). After 2 weeks, mice underwent 18FDG-PET/CT. Calliper-measured tumour growth (Δvol) and final tumour volume (Volcal), 18FDG-PET metabolically active volume (Volmet), mean metabolism (Metmean), and maximum metabolism (Metmax) were measured. Twenty-four texture features were compared between treated and untreated mice. Immunohistochemical mean tumour vascular density (MVD) was estimated by anti-CD-34 staining after tumour resection.ResultsTreated mice had significantly lower MVD (p=0.032), confirming anti-angiogenic therapeutic effect of bevacizumab. None of the conventional measures were different between the two groups: Δvol (p=0.9), Volcal (p=0.7), Volmet (p=0.28), Metmax (p=0.7), or Metmean (p=0.32). One texture parameter, GLSZM-SZV (visually indicating that the 18F-FDG PET images of treated mice comprise uniformly sized clusters of different activity)) had significantly different means between the two groups of mice. Conclusions18F-FDG PET derived texture parameters, particularly GLSZM-SZV, may be valid biomarkers of tumour response to treatment with bevacizumab, before change in volume.