Treatment of cancer accounts for an increasing level of healthcare expense although patient morbidity and mortality remain relatively high. Current methods for assessing the extent of immune cell infiltration into cancers require invasive biopsy procedures that cannot be done on the same tumor over time, thus precluding longitudinal tracking of immune responses in patients. In the current project, we propose to develop a novel molecular imaging probe for visualization of macrophage infiltration into tumors. Specifically, we aim to develop a microbubble contrast agent targeted to a molecular marker of MHCII positive macrophages, thought to be indicative of a tumor rejection response. In this Phase I proposal, we will use an anti-mouse MHC class II antibody as a targeting ligand. Antibodies will be conjugated to the surface of an ultrasound molecular imaging agent using proven biocompatible coupling chemistry. We will validate ligand conjugation and microbubble stability, and assess the targeting efficacy of the resultant microbubble formulations in vitro and in a mouse model of tumor progression. We will use this imaging agent to quantitatively track the influx of macrophages in paired mouse models of tumor rejection and growth. Successful completion of these aims will result in a molecular imaging probe that may be used to accurately and rapidly identify the quality and quantity of tumor infiltrating macrophages, with applications as both a lie science research reagent and as a clinical diagnostic.
Immune cell infiltration into tumors is used to predict prognosis, but this is limited to immunohistochemical approaches of biopsied material and has not been done longitudinally. In the current project, we aim to develop a diagnostic and prognostic imaging test to detect infiltration of MHCII macrophage populations into growing versus rejecting tumors. Non-invasive imaging of immune cell infiltration into tumors in real time will allow for prompt and powerful assessment of antitumor immune responses, which can direct patient therapy and provide important prognostic information.
