Abstract 1150: Targeted immunoPET imaging of prostate cancer using a novel CD133 antibody

Abstract Prostate cancer is one of the most frequently diagnosed malignancies and the second leading cause of cancer related death among American men. Aggressive variant prostate cancer (AVPC) accounts for approximately 33% of all prostate cancer-related deaths and is characterized by visceral metastasis, minimal responses to current therapies, and poor overall prognosis. The current disease monitoring strategy for AVPC is positron emission tomography - computed tomography (PET/CT) with [18F]-fluorodeoxyglucose (FDG), which is not specific to prostate cancer cells and thus is inadequate in many cases. As such, novel targeted imaging agents are urgently needed for earlier detection and better monitoring of AVPC. The transmembrane glycoprotein, CD133, is overexpressed in AVPC and we have identified a single chain variable fragment, termed HA10, which preferentially recognizes a glycosylation-independent epitope on CD133. Further characterization of HA10 revealed that it was able to identify CD133 in cells, patient tissue samples, and in vivo xenograft models using fluorescent imaging. The purpose of this study was to investigate the performance of the radioimmunoconjugate, 89Zr-HA10, for µPET/CT imaging in preclinical models of prostate cancer. HA10 was conjugated to p-SCN-Deferoxamine (DFO) and then radiolabeled with [89Zr]Zr-oxalate at room temperature. Parental (CWR-R1) and CD133-transduced (CWR-R1CD133) prostate cancer cell lines were implanted subcutaneously into male athymic nu/nu mice. Mice were administered 180 µCi of 89Zr-HA10 via tail vein injection and µPET/CT imaging was conducted at 24, 48, 72, and 144 hours post-injection. The 89Zr-HA10 construct was successfully labeled with a radiochemical purity >99% as determined by radio-thin layer chromatography. Specificity of 89Zr-HA10 was demonstrated for CD133-positive tumors with strong tumoral uptake detection from 24-72 hours. Furthermore, the margins of the CD133-positive tumors were clearly defined following 3D reconstruction of the µPET/CT images. These studies suggest that 89Zr-HA10 is a promising immunoPET imaging agent for AVPC and potentially other CD133-positive cancer subtypes. Moreover, the use of 89Zr-HA10 as a radiotracer will facilitate a more selective strategy for diagnosis and disease monitoring of these patients compared to the conventional FDG radiotracer. Further studies seek to evaluate the potential of 89Zr-HA10 to detect small metastatic lesions in vivo. Citation Format: Paige Glumac, Aaron LeBeau. Targeted immunoPET imaging of prostate cancer using a novel CD133 antibody [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1150.