Pet-Mri Imaging Of Reactive Macrophages In An Orthotopic Model Of Ovarian Cancer.

Abstract Ovarian cancer is a lethal gynecologic malignancy and the fifth leading cause of cancer-related deaths in women in the United States. Early detection is a critical unmet need, as patients have significantly improved prognosis when a tumor is discovered at an early stage, and disease staging for prognosis and treatment strategy is critical to ensure proper clinical management. Major limitations of radiological evaluation of ovarian cancer arise from the inability to consistently detect small lesions. The availability of multiplexed hybrid imaging systems, such as simultaneous PET-MRI scanners, presents unique opportunities to combine the strengths of anatomic, physiologic and molecular detection within a single exam for the purpose of early detection and staging of ovarian cancer. Tumor associated macrophages (TAMs) play a critical role in ovarian cancer and are among several promising targets in host-directed therapies in cancer. Here, we will combine the anatomic imaging capabilities of MRI with the highly sensitive molecular imaging capabilities of PET in an orthotopic syngeneic model of ovarian cancer, using [124I]iodo-DPA-713, a macrophage-specific imaging agent to define host signatures to detect and stage ovarian cancer. [124I]DPA-713 is a low molecular weight probe that is selectively trapped within reactive phagocytes in both peripheral and central nervous system tissues, including TAMs, and exhibits very low background retention. Using PET-MRI imaging, this allows for excelling visualization of ovaries and the peritoneal environment. Pieces of ID8-Defb29-VEGF tumor were orthotopically implanted onto the ovary of C57BL6 mice. Subcutaneous ID8-Defb29-VEGF tumors were also imaged for comparison. Bioluminescent imaging (BLI) was used to follow tumor progression, as these cancer cells constitutively express luciferin. Experiments were performed in mice presenting with different disease stages, from early stage when tumors are less than 3 mm with no metastases, to late stage with metastases and ascites present. BLI data were used to stratify the mice into different groups. Specific uptake of the radiotracer was observed within and proximal to the primary tumor at early stages. At later stages, uptake was observed in the peritoneal ascitic fluid and within metastases in the lungs, in addition to clear halos surrounding the primary tumor. These studies are clinically translatable and will facilitate non-invasive detection of a nursery of tumor supporting reactive macrophages. They will also provide insights into ovarian cancer progression that will complement emerging host-directed therapeutics destined for the clinic. Supported by the Hopkins Cancer Center Imaging Fund. Citation Format: Catherine Foss, Desmond Jacob, Flonné Wildes, Marie-France Penet. PET-MRI imaging of reactive macrophages in an orthotopic model of ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2809.