Assessment of the antiangiogenic therapy of avastin in an animal colon cancer model with DCE-MRI and a biodegradable macromolecular contrast agent

Introduction: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a non-invasive imaging modality for tumor characterization and evaluating tumor response to anti-cancer therapies [1-2]. Current clinical MRI contrast agents are small molecular contrast agents, which have limitations for accurate and quantitative measurement of tumor vascular parameters due to their non-selective extravasation into the extracellular space of tumor and normal tissues [3]. Although macromolecular contrast agents (MMCAs) are effective for tumor characterization and evaluating anticancer therapeutic efficacy in DCE-MRI in preclinical studies, their slow and incomplete elimination limits their development for clinic application. A new class of polydisulfide-based macromolecular Gd(III) complexes has been recently developed as biodegradable macromolecular MRI contrast agents to facilitate the excretion of Gd(III) chelates after the MRI examinations [4]. These agents initially behave as macromolecular agents, and then degrade in vivo into low molecular weight Gd(III) complexes that excrete rapidly from the body via renal filtration [5]. In this study, we investigated the efficacy of a promising biodegradable macromolecular contrast agent, Gd-DTPA cystamine copolymers (GDCC), for quantitatively assessing tumor microvascular characteristics and monitoring therapeutic efficacy of antiangiogenic therapy with Avastin® by DCE-MRI.