Translational imaging endpoints to predict treatment response to novel targeted anticancer agents

Abstract

Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) Criteria have been traditionally used for the evaluation of therapeutic response to chemotherapeutic treatment regimens. They determine anatomic criteria for patients response to anti-cancer therapy based on morphological measurements of each target lesion. While this assessment is justified for cytotoxic (chemotherapeutic) drugs, it is now recognized that morphological imaging protocols are poorly suited to the evaluation of the efficacy of novel signal transduction inhibitors (STIs) which exhibit cytostatic rather than cytotoxic properties. New imaging technologies are now designed to evaluate, in a functional manner, modifications in tumor metabolic activity, cellularity, and vascularization before a reduction in tumor volume can be detected. Introduction of physiological imaging end-points, derived from dynamic contrast-enhanced (DCE) imaging protocols--including magnetic resonance imaging (MRI), computed tomography (CT) and ultrasound (US)--allow for early assessment of disruption in tumor perfusion and permeability for targeted anti-angiogenic agents. Diffusion-weighted MRI (DWI) provides another physiological imaging end-point since tumor necrosis and cellularity are seen early in response to anti-angiogenic treatment. Changes in glucose and phospholipid turnover, based on metabolic MRI and positron emission tomography (PET), provide reliable markers for therapeutic response to novel receptor-targeting agents. Finally, novel molecular imaging techniques of protein and gene expression have been developed in animal models followed by a successful human application for gene therapy-based protocols.