A Genetically Encoded Magnetic Resonance Imaging Reporter Enables Sensitive Detection and Tracking of Spontaneous Metastases in Deep Tissues


 Metastasis is the leading cause of cancer-related death. However, it remains a poorly understood aspect of cancer biology, and most preclinical cancer studies do not examine metastasis, focusing solely on the primary tumor. One major factor contributing to this paradox is a gap in available tools for accurate spatiotemporal measurements of metastatic spread in vivo. Here, our objective was to develop an imaging reporter system that offers sensitive three-dimensional detection of cancer cells at high resolutions in live mice. An organic anion-transporting polypeptide 1b3 (oatp1b3) was utilized as a magnetic resonance imaging (MRI) reporter gene, and its sensitivity was systematically optimized for in vivo tracking of viable cancer cells in a spontaneous metastasis model. Metastases with oatp1b3-MRI could be observed at the single lymph node level and tracked over time as cancer cells spread to multiple lymph nodes and different organ systems in individual animals. While initial single lesions were successfully imaged in parallel via bioluminescence, later metastases were largely obscured by light scatter from the initial node. Importantly, MRI could detect micro-metastases in lung tissue estimated to comprise of as few as 1000 cancer cells. In summary, oatp1b3-MRI enables longitudinal tracking of cancer cells with combined high resolution and high sensitivity that provides 3D spatial information and the surrounding anatomical context.