Abstract 4535: Molecular-genetic imaging of prostate cancer.

Abstract

Abstract Cancer-specific promoters, such as the progression elevated gene-3 or the astrocyte elevated gene promoters, PEG-Prom and AEG-Prom, respectively, can be used as molecular genetic imaging instruments for tumor-selective imaging of cancer. We have previously shown this in experimental models of metastatic breast cancer and melanoma using bioluminescence imaging (BLI) and single photon emission computed tomography with computed tomography (SPECT/CT). Here we show that we can express PEG-Prom and AEG-Prom selectively in PC3-ML (human bone metastatic derived prostate cancer) cells and use these constructs for imaging prostate cancer in vivo. PC3-ML cells were transfected with firefly luciferase (FLuc) or the herpes simplex type I thymidine kinase (HSV1-tk), and validated for suitable transfection through bioluminescence and [125I]FIAU cell uptake assays, respectively. PC3-ML cells were administered through intra-cardiac injection to allow widespread metastases. A linear polyethyleneimine (l-PEI) nanoparticle was used for intravenous (IV) delivery of the promoter constructs to animals bearing metastases. PEG-Prom- and AEG-Prom-driven imaging reporter gene expression was monitored by small animal BLI and by SPECT/CT after IV administration of D-luciferin or [125I]FIAU, respectively. Both BLI and SPECT/CT imaging demonstrated tumor-specific PEG-Prom and AEG-Prom activity in the model of metastatic prostate cancer but not in control. Using the thoracic cavity and tibia as the regions of interest (ROI), quantification of the BLI data (n=6) at the 48 h time point after reporter gene delivery showed a range of 16- to 19-fold higher accumulation of FLuc in the metastasis group compared to control for PEG-Prom and AEG-Prom, respectively. BLI results were confirmed by histopathology, immunohistochemistry and western blot. Quantification of the SPECT/CT data (n=5) at the 56 h time point after reporter gene and 8 h after [125I]FIAU delivery showed a 3- to 11-fold higher accumulation of [125I]FIAU, depending on the tumor burden, in the group bearing metastases compared to control for AEG-Prom. Metastatic nodules detected by the SPECT/CT imaging were confirmed by pathology. The results demonstrate the potential of systemically delivered, PEG-Prom- and AEG-Prom-driven constructs for enabling the imaging of metastatic prostate cancer in vivo. Citation Format: Akrita Bhatnager, Kathleen Gabrielson, Paul B. Fisher, Martin G. Pomper. Molecular-genetic imaging of prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4535. doi:10.1158/1538-7445.AM2013-4535