Abstract 1145: Biomarker-driven molecular imaging of prostate cancer using the PEG10 promoter

The retrotransposon-derived paternally expressed gene 10 (PEG10) protein is ordinarily expressed at high levels in the placenta. The over-expression of PEG10 has been documented in a number of malignancies including hepatocellular carcinoma and leukemia. Recently, it was discovered that PEG10 isoforms promoted the progression of prostate adenocarcinoma to a highly lethal non-androgen receptor (AR) driven subtype called aggressive variant prostate cancer (AVPC). In this study, we found that PEG10 was also expressed in castration-resistant PCa possessing constitutively active AR-splice variants in addition to AR-negative AVPC. We subsequently developed a molecular genetic imaging strategy for the non-invasive imaging of PCa by utilizing the cancer specificity of the PEG10 promoter to drive the expression of reporter genes. The transcriptional output of the PEG10 promoter was enhanced to enable high expression of reporter genes by multiple imaging modalities and immunoassay. By using this PEG10 promoter upstream of a reporter gene in a plasmid, we were able to detect PCa by fluorescence and positron emission tomography (PET) imaging after systemic administration of the plasmid in mice. This method also allowed for the detection of PCa by an immunoassay of mouse urine. Our study demonstrates a pre-clinical proof-of-concept that the PEG10 promoter is a powerful and specific tool that can be utilized for non-invasive detection of highly lethal PCa subtypes. This biomarker imaging technology has the potential to improve detection and can be further modified for therapeutic applications. Citation Format: Mariya Shapovalova. Biomarker-driven molecular imaging of prostate cancer using the PEG10 promoter [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 1145.