Molecular Imaging of Tumor-Associated Angiogenesis Using a Novel Magnetic Resonance Imaging Contrast Agent Targeting αvβ3 Integrin

Abstract

The recent introduction of biological anticancer therapy has renewed the interest in functional imaging of tumor-associated angiogenesis (TAA) as a tool to monitor early therapy response. The present study evaluated imaging of TAA using P1227, a novel, small molecular magnetic resonance imaging (MRI) probe targeting αvβ3 integrin. HT29 human colorectal cancers were grown in athymic mice. Dynamic MRI was performed using a three-dimensional VIBE sequence up to 110 min after injection of P1227 or gadolinium-tetraazacyclododecane tetraacetic acid (Gd-DOTA). Specificity was assessed by using P1227 1h after intravenous administration of the αvβ3 inhibitor cilengitide. Regions of interest were drawn encompassing the tumor rim and normal muscle. Imaging data were compared with microvessel density and αvβ3 expression. Using P1227, specific enhancement of the angiogenic tumor rim, but not of normal muscle, was observed, whereas Gd-DOTA enhanced tumor and normal muscle. After administering cilengitide, enhancement with P1227, but not with DOTA, was significantly suppressed during the first 20min. When using P1227, a significant correlation was observed between normalized enhancement of the tumor rim and immunohistochemical αvβ3 integrin expression. Molecular MRI using a small monogadolinated tracer targeting αvβ3 integrin and moderate magnetic field strength holds promise in assessing colorectal TAA.