Cancer-induced changes in systemic intravascular monocyte dynamics revealed by MRI single cell tracking in a murine breast cancer model

Abstract Objectives In cancer, monocytes with patrolling-like behavior have been associated with antitumoral effects, but their intravascular motion is currently concealed to noninvasive imaging techniques. This study aimed to evaluate systemic monocyte intravascular patrolling-like behavior during tumor growth, immunotherapy, and splenectomy, using single-cell tracking with preclinical time-lapse brain magnetic resonance imaging (MRI). Materials and methods In a murine syngeneic breast cancer model (4T1, 67NR), time-lapse MRI (repetitive T2*-weighted gradient-echo sequence after in vivo labeling with iron oxide nanoparticles for monocyte detection) of the brain was conducted using a 9.4 T small animal MRI. Control mice were either naive or received sham injections. Additionally, time-lapse MRI was conducted during immunotherapy or following splenectomy in tumor-bearing and tumor-free mice. Individual cells were identified as hypointensities. Tumors were harvested for ex vivo analysis. Results The number of detected cells within the brain, distant from the tumor, changed during cancer growth. The cell count was significantly lower for tumor-bearing mice compared to controls. In mice bearing 4T1 tumors, the cell count was significantly lower on day 1 and 9 compared to mice bearing 67NR tumors. During immunotherapy, the monocyte count was significantly lower compared to control, but only in the presence of a tumor. Splenectomy reduced the tumor-associated effect on monocyte dynamics in both low- and highly malignant tumors. Conclusion Based on an exemplary murine breast cancer model, both cancer and immunotherapy change systemic intravascular monocyte patrolling-like behavior early during tumor growth distant from the tumor, an observation that is dependent on the grade of malignancy and the presence of splenic reservoirs. Key Points Question Do tumors alter systemic intravascular monocyte dynamics during tumor growth, immunotherapy, and splenectomy at distant sites, and can such changes be detected noninvasively? Findings In murine breast cancer, time-lapse MRI revealed reduced monocyte patrolling-like behavior during tumor growth and immunotherapy, influenced by malignancy grade and splenic reservoirs. Critical Relevance Noninvasive single-cell MRI tracking provides novel insights into systemic immune dynamics in cancer, potentially enabling future monitoring of tumor-immune interactions, therapeutic responses, and immune modulation beyond conventional assessment of tumor burden or tumor microenvironment composition.