Non-invasive visualization of mast cell recruitment and its effects in lung cancer by optical reporter gene imaging and glucose metabolism monitoring.

Abstract

The inability to monitor the in vivo dynamics of mast cells (MCs) limits the better understanding of its role in cancer progression. Here, we report on noninvasive imaging of MC migration to tumor lesions in mice and evaluation of the effects of migrated MCs on tumor progression through reporter gene-based in vivo optical imaging and glucose metabolism monitoring in cancer with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) in vitro and in vivo. Murine MCs (MC-9) and Lewis lung cancer cells (LLC) expressing an enhanced firefly luciferase (effluc) gene were established, termed MC-9/effluc and LLC/effluc, respectively. MC-9/effluc cell migration to LLC tumor lesions was initially detected within 1 h post-transfer and distinct bioluminescence imaging signals emitted from MC-9/effluc cells were observed at tumor sites until 96 h. In vivo optical imaging as well as a biodistribution study with ¹⁸F-FDG demonstrated more rapid tumor growth and upregulated glucose uptake potentially associated with MC migration to tumor lesions. These results suggest that the combination of a reporter gene-based optical imaging approach and glucose metabolism status monitoring with ¹⁸F-FDG represents a promising tool to better understand the biological role of MCs in tumor microenvironments and to develop new therapeutic drugs to regulate their involvement in enhanced tumor growth.