Microendoscopy for periodic intravital end-to-end tumor imaging of cancer cells.

The spatiotemporal heterogeneity in intratumor proliferative behavior of cancer cells deeply affects tumor environment characteristics and the efficacy of anticancer treatments. Thus, intravital imaging with unlimited imaging depth and cellular-level resolution is greatly desired. We developed an optical-fiber-bundle-based microendoscope with a genetically encoded fluorescent ubiquitination-based cell-cycle indicator (Fucci) system to achieve the intravital, periodic, and multicolor end-to-end imaging of the proliferative activity of cancer cells at a cellular-level resolution. This technique enabled the periodic visualization of spatiotemporal cellular responses, including cell-cycle arrest and resumption, and nuclear enlargement following the administration of anticancer drugs in living mice. It was suggested that proliferating cell ratio and nuclear enlargement in cancer cells at the surface region of tumor characterized by abundant vascular invasion contribute to aggressive tumor regrowth after chemotherapy. The application of this technique can accelerate innovation in cancer biology and therapeutics.