Multiparametric Monitoring of Early Response to Antiangiogenic Therapy: A Sequential Perfusion CT and PET/CT Study in a Rabbit VX2 Tumor Model

Abstract

Introduction: The perfusion CT has particularly seen increasing use as a method to quantify tumor vascularity and to monitor antiangiogenic response. Although the application of functional imaging such as FDG-PET and tumor perfusion imaging as markers of tumor response has been increasing in both research and clinical settings, these functional imaging techniques have been used in isolation. Therefore, the purpose of this study was to undertake dual analysis of tumor perfusion and glucose metabolism after initiation of bevacizumab, a monoclonal antibody against the vascular endothelial growth factor, using perfusion CT and FDG-PET/CT in a VX2 tumor model in rabbits and to assess the possible added value of variable FDG-PET-derived indices to perfusion CT in monitoring early treatment response. 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 two 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.