Abstract 5224: Tracking the longitudinal physiological and vascular morphology changes in response to anti-angiogenesis treatment in breast tumors

Abstract

Abstract VEGF and its receptor (VEGFR2 or flk1/KDR) play critical roles in tumor angiogenesis, which is essential for tumor growth and metastasis. The objective of this study is to track and quantify the longitudinal intra-tumor heterogeneous response to anti-VEGFR2 treatment using a combination of imaging modalities: dynamic contrast-enhanced CT (DCE-CT) and photoacoustic computed tomography (PCT). DCE-CT is used to measure vascular physiology and PCT is used to monitor its morphological changes based on its hemoglobin status within the tumor. A cohort of athymic mice bearing MCF-7VEGF (MCF-7 cells transfected with VEGF gene) tumors were divided into three groups: a control group (received non-specific, rat immunoglobulin IgG1, i.v.), a low dose therapeutic group (30 mg/kg DC101, i.v.), and a high dose therapeutic group (150 mg/kg DC101, i.v.). Twenty-four hours prior to treatment, baseline DCE-CT and PCT scans were acquired. Successive scans were taken 2 days, 1 week, and 2 weeks post treatment to track both physiological and morphological changes. For the former, a two-compartmental kinetic model is fit to contrast enhanced curves on a voxel-by-voxel basis to determine tumor physiological parameters of perfusion (F), permeability-surface area (PS), fractional plasma volume (fp) and fractional interstitial space (fis). Maximum intensity profiles (MIPs) and hemoglobin profiles were extracted from PCT images. The preliminary results show a dose dependent response to DC101 treatments. Two days post treatment, low dose reduced F by 36% and fp by 22%; high dose reduced F by 72% and fp by 39%. Tumor perfusion remained reduced two weeks post treatment, while fp in treated mice rebounded to similar levels as the control group after one week and exceeded the control group by week two. This decoupling of fp and F over time indicates a step-wise progressive nature to the formation of a vascular network and its functionality associated with the VEGF/VEGFR2 pathway. Photoacoustic results confirm the link between the changes in vascular morphology and physiology, and provide an in vivo link between vascular structure and function in response to anti-angiogenic therapy. Future work will focus on measuring the oxygen saturation levels and hemoglobin concentration in tumors by analyzing the spectroscopic information afforded by PCT. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5224.