Near infrared imaging of Mer tyrosine kinase (MERTK) using MERi-SiR reveals tumor associated macrophage uptake in metastatic disease

• Published in: Chemical communications (Cambridge, England) Vol. 54; no. 1; p. 42
• Main Authors: Miller, Miles A, Kim, Eunha, Cuccarese, Michael F, Plotkin, Alec L, Prytyskach, Mark, Kohler, Rainer H, Pittet, Mikael J, Weissleder, Ralph
• Format: Journal Article
• Language: English
• Published: England 01-01-2018
• Subjects: Animals; Binding Sites; c-Mer Tyrosine Kinase - antagonists & inhibitors; c-Mer Tyrosine Kinase - genetics; c-Mer Tyrosine Kinase - metabolism; Cell Line, Tumor; Cell Proliferation; Fluorescent Dyes - chemical synthesis; Fluorescent Dyes - chemistry; Macrophages - cytology; Macrophages - metabolism; Macrophages - pathology; Mice; Microscopy, Confocal; Molecular Docking Simulation; Neoplasm Metastasis; Neoplasms - metabolism; Neoplasms - pathology; Protein Structure, Tertiary; Pyrimidines - chemistry; Pyrroles - chemistry; RNA Interference; RNA, Small Interfering - metabolism; Signal Transduction; Spectroscopy, Near-Infrared; Structure-Activity Relationship
• ISSN: 1364-548X
• DOI: 10.1039/c7cc07581b

The receptor tyrosine kinase Mer (MERTK) is a promising drug target in cancer, where it can influence the metastasis-promoting signaling of both tumor cells and immune cells alike; however, no small molecule probes currently exist to selectively image Mer. In this work, we design and synthesize a selective near-infrared fluorescent molecular probe of Mer (MERi-SiR). Confocal microscopy of metastases in mice reveals predominant probe accumulation in Mer-expressing tumor-associated macrophages.