The genetic element, known as progression elevated gene-3 (PEG-3) promoter, can be used to image metastases in multiple animal models of human melanoma and human breast metastasis, according to a study published online Dec. 12 in the journal Nature Medicine.
The work, a collaborative effort between Virginia Commonwealth University (VCU) in Richmond and Johns Hopkins University in Baltimore, could lead to improved and earlier detection of tumors and metastases in patients and could allow clinicians to monitor the cancer's response to therapy.
Molecular genetic imaging is advancing from a valuable preclinical tool to a guide for patient management, according to the study authors. 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.
In this study, the researchers showed that PEG-3 promoter, derived from a rodent gene mediating tumor progression and metastatic phenotypes, could 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.
“The PEG-promoter is the unique aspect of this innovative imaging approach. It is a cancer-specific region of the PEG-3 gene that selectively expresses when in cancer cells. It has minimal expression in normal tissue or animals without cancer,” said Paul B. Fisher, PhD, professor and chair of the department of human and molecular genetics at VCU.
“This new, non-invasive imaging approach will allow researchers to test chemoprevention strategies and to use repeat applications to follow the course of therapy over time and more accurately define therapeutic outcome and response to therapy than using current methodologies,” Fisher said.
“The potential for this approach to translate into a more effective mode of imaging in humans is extremely high. The benefits to patients would be enormous. One could diagnose tumor formation and cancer that has spread earlier and therefore allow testing of effective therapies. When combined with a therapeutic agent — a radiation emitting compound, a chemotherapeutic agent, or a cytokine such as melanoma differentiation-associated gene-7/interleukin-24 — it could in the future permit both imaging and therapy of cancers and metastases,” Fisher added.