| In the field of cancer imaging, the molecular-genetic imaging approach is advancing from a valuable preclinical tool to guiding patient management. Tissue-specific promoters can be used to delineate their downstream reporter gene expression in certain tissues, particularly when coupled with an appropriate amplification mechanism. PEG-Prom is the promoter of progression elevated gene-3 (Peg-3), a rodent gene associated with malignant transformation and tumor progression. PEG-Prom drives tumor-specific gene expression in a wide spectrum of human cancer cell lines. Based on the tumor-specific activity of PEG-Prom we have developed a systemically administrable imaging system for cancer metastasis.;We generated PEG-Prom-driven firefly luciferase (Luc) and HSV1 thymidine kinase (HSVI-TK) reporter constructs, pPEG-Luc and pPEG-HSV1tk, respectively and delivered them in vivo using a nonviral vehicle, linear polyethyleneimine (1-PEI). Experimental metastasis models of human breast cancer (BCa) and melanoma (Mel) along with controls (Ctrl) were systemically delivered with pPEG-Luc/PEI polyplex followed by serial bioluminescence imaging (BLI). Imaging results were confirmed by immunohistochemistry and gross pathology. Similarly, pPEG-HSV1tk/PEI was delivered to BCa, Mel and Ctrl animals followed by serial SPECT-CT imaging with [125I]FIAU as the radiotracer. Translational potential of our PEG-Prom-mediated imaging system was assessed through its comparison with [18F]EDG-PET, the current clinical standard for cancer imaging.;Both BLI and SPEC-CT imaging demonstrated tumor-specific PEG-Prom activity in the BCa and Mel models, but not in the Ctrl. Histological analysis confirmed the localization of reporter expression in metastatic nodules. Quantification of the lung SPECT data showed 31-fold higher accumulation of [125I]FIAU in the Mel group compared to the Ctrl. Systemic metastases were detected and localized based on whole body SPECT-CT images, which were comparable to the FDG-PET imaging results.;In conclusion, PEG-Prom was used to drive imaging reporters selectively to enable detection of micrometastatic disease in murine models of human melanoma and breast cancer using bioluminescence and radionuclide-based molecular imaging techniques. Because of its strong promoter activity, tumor specificity, and systemic delivery using a nonviral vehicle, the PEG-Prom-mediated imaging system may represent a new system to facilitate cancer imaging and therapy with the capacity for clinical translation. |
