Tumor-specific imaging through progression elevated gene-3 promoter-driven gene expression

Bhang and colleagues have developed a tumor-specific imaging strategy that uses the progression elevated gene-3 (PEG-3) promoter, known to be specifically associated with malignant transformation, to selectively drive the expression of luciferase or herpes simplex virus 1 thymidine kinase reporters. Systemic delivery of PEG-3 promoter–driven constructs using a nonviral gene delivery vehicle allowed detection of both primary tumors and micrometastatic disease in mouse models of human melanoma and breast cancer. Molecular-genetic imaging is advancing from a valuable preclinical tool to a guide for patient management. The strategy involves pairing an imaging reporter gene with a complementary imaging agent in a system that can be used to measure gene expression or protein interaction or track gene-tagged cells in vivo . Tissue-specific promoters can be used to delineate gene expression in certain tissues, particularly when coupled with an appropriate amplification mechanism. Here we show that the progression elevated gene-3 (PEG-3) promoter, derived from a rodent gene mediating tumor progression and metastatic phenotypes, can be used to drive imaging reporters selectively to enable detection of micrometastatic disease in mouse models of human melanoma and breast cancer using bioluminescence and radionuclide-based molecular imaging techniques. Because of its strong promoter activity, tumor specificity and capacity for clinical translation, PEG-3 promoter–driven gene expression may represent a practical, new system for facilitating cancer imaging and therapy.