Full Project D: Synthesis and Preclinical Evaluation of Targeted, Iron-Based MRI Contrast Agents to Enhance Ovarian Cancer Detection and Treatment Scheduling
Co-Investigators
Raphael Raptis, Ph.D., Professor, Department of Chemistry, University of Puerto Rico-Rio Piedras, Rio Piedras, Puerto Rico
Jim Klostergaard, Ph.D., Professor, Department of Molecular & Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
Ovarian cancer remains the most lethal gynecologic malignancy, with only incremental improvements in survival rates over the last decades. Due to the absence of appropriate screening targets and clearly-defined risk factors for the majority of ovarian cancers, carcinomatous involvement of the peritoneum is already present in the majority of newly-diagnosed patients; ominously, this tumor burden alone frequently determines survival.
Non-invasive detection of early therapeutic responses of ovarian cancer already in the peritoneum in the contexts of minimal residual disease following debulking, as well as detection of the earliest evidence of relapse of such disease after treatment-induced remission, might prove invaluable for optimal patient management and treatment intervention.
Specific Aims
To evaluate the ability of non-targeted as well as targeted formulations of the proprietary lead Fe8-compound and its water-soluble conjugates to enhance MR imaging of i.p. human ovarian carcinoma xenograft models
To develop/select thioaptamers with high affinity for CD44 family members, parental and/or selected splice variants
To synthesize appropriate chemically functionalized derivatives of the lead Fe8-cluster, which will allow the attachment of the anti-CD44 aptamers, and to determine whether the CD44 aptamer-Fe8-cluster conjugate improves the MR imaging sensitivity of i.p. CD44+ ovarian carcinoma xenografts, by comparison to the HA-Fe8 CA, as well as to non-targeted complexes
Our goal and expectation is that at the end of this study, we will be in a position to select a lead CA formulation for further pre-clinical development and to subsequently follow a track to clinical evaluation.