Abstract
Objectives. To perform dual analysis of tumor perfusion and glucose metabolism using perfusion CT and FDG-PET/CT for the purpose of monitoring the early response to bevacizumab therapy in rabbit VX2 tumor models and to assess added value of FDG-PET to perfusion CT. Methods. Twenty-four VX2 carcinoma tumors implanted in bilateral back muscles of 12 rabbits were evaluated. Serial concurrent perfusion CT and FDG-PET/CT were performed before and 3, 7, and 14 days after bevacizumab therapy (treatment group) or saline infusion (control group). Perfusion CT was analyzed to calculate blood flow (BF), blood volume (BV), and permeability surface area product (PS); FDG-PET was analyzed to calculate SUVmax, SUVmean, total lesion glycolysis (TLG), entropy, and homogeneity. The flow-metabolic ratio (FMR) was also calculated and immunohistochemical analysis of microvessel density (MVD) was performed. Results. On day 14, BF and BV in the treatment group were significantly lower than in the control group. There were no significant differences in all FDG-PET-derived parameters between both groups. In the treatment group, FMR prominently decreased after therapy and was positively correlated with MVD. Conclusions. In VX2 tumors, FMR could provide further insight into the early antiangiogenic effect reflecting a mismatch in intratumor blood flow and metabolism.
Highlights
Angiogenesis is an essential component of tumor growth, invasion, and metastasis
Perfusion computed tomography (CT) data were incomplete: perfusion CT on day 3 of one rabbit in the control group and baseline perfusion CT of another rabbit in the treatment group were not suitable for imaging registration owing to movement during CT scanning
The development and validation of biomarkers for the prediction of response to antiangiogenic therapy is an area of increasing importance, given recent concerns surrounding the effectiveness of such therapies in prolonging patient survival as well as their potential effects on metastasis [26]
Summary
Angiogenesis is an essential component of tumor growth, invasion, and metastasis. Recently, with the continued development of antiangiogenic drugs that target the inhibition of tumor angiogenesis, techniques that can evaluate tumor angiogenesis have been emphasized in clinical practice. Quantitative computed tomography (CT) and magnetic resonance (MR) imaging kinetic parameters may be used to obtain insights into underlying tissue pathophysiologic processes of a variety of treatments, allowing prediction of treatment response or monitoring of their effects [2] The Scientific World Journal seen increasing use as a method to quantify tumor vascularity and to monitor antiangiogenic response [3,4,5,6,7,8] Another modality that has been used to evaluate the angiogenesis of tumors is positron emission tomography (PET). They suggested that measurement of the pharmacodynamic effects of antiangiogenic therapies with FDG at an earlier time point (within days) may be more appropriate to monitor changes in cell viability
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