Prostate cancer is the second-leading cause of cancer death for men in the U.S. While many patients have localized disease, a significant number of patients have disease recurrence due to undetected lymph node metastases at the time of initial diagnosis Although current imaging technologies such as magnetic resonance imaging (MRI) is used for pre-operative evaluation of metastatic spread into lymph nodes, poor sensitivity and low accuracy restrict their utility for precise identification. As a consequence, patients receive treatment plans that reflect an inaccurate cancer stage, significantly impacting their survival rates. Thus, detection of lymph node metastases at the molecular level is of urgent need. To that end, we propose to develop a molecular MR imaging nanodiagnostic tool based on peptide amphiphile micelles that targets the C-chemokine receptor 2 (CCR2) highly expressed on prostate cancer cells and lymph node metastases Specifically, in Aim 1, we will incorporate gadolinium into CCR2 micelles and measure MR contrast ability and targeting ability using prostate cancer cells and an in vitro lymph node model. In Aim 2, we will assess the pharmacokinetic properties, safety, and detection of metastatic lymph nodes using MRI by CCR2-Gd micelles in murine prostate cancer models. Given our compelling preliminary data and the expertise of our strong collaborative team spanning nanomedicine (Chung, Viterbi), molecular imaging (Jacobs, Keck), prostate cancer, (Gross, Ellison Institute), and the lymphatic system (Wong, Keck), we are uniquely qualified to successfully drive this new area of research towards patient use. If successful, our results will lay the groundwork for developing nanodiagnostic tools that can simultaneously detect and treat lymph node metastases broadly across many cancers.
