Immune activity within tumors and secondary lymphoid organs critically influences cancer progression, metastasis, and treatment response. We present a dual-nucleus (1H/19F) molecular MRI platform for non-invasive, high-resolution profiling of the tumor-immune microenvironment in immunocompetent mouse models. Tumor viability was visualized by engineering breast cancer cells to express a novel mouse-derived 1H MRI reporter gene, enabling in vivo differentiation of viable and necrotic tumor regions. Concurrently, 19F MRI using perfluorocarbon (PFC) nanoemulsions enabled longitudinal tracking of immune cell infiltration, extending beyond conventional tumor-associated macrophage–focused approaches. Ex vivo analyses confirmed PFC uptake across diverse immune subsets, with tissue- and context-specific variations in 19F signal driven by differences in cell abundance and labeling efficiency. Notably, 19F MRI revealed a predominantly myeloid signature within tumors, a mixed myeloid/lymphoid profile in the spleen, and a lymphoid-skewed signal in tumor-draining lymph nodes. By integrating tumor-specific 1H imaging with immune-resolving 19F imaging, this single-modality platform offers a comprehensive view of tumor architecture and immune cell presence within tumors. Our imaging approach enables discrimination of immunologically dense tumors and offers critical insights into the interpretation of 19F MRI signals within immune competent animal models, providing an immunoimaging tool that increases the translational relevance of preclinical therapeutic insights.
McRae et al. (Mon,) studied this question.