Presenter(s)
B. Meng, K. Tang, A. Davis, J. Lee, and E. Ahrens; University of California San Diego, San Diego, CA
Purpose/Objective(s): The interplay of radiation and tumor associated macrophage (TAM) plays a critical role in the complex radiation induced immune modulation effect. The ability to monitor TAM response to irradiation can guide the treatment stratification to enhance anti-tumor immune responses and increase the therapeutic efficacy of radiotherapy. Current techniques to measure TAM density require biopsy of tumor specimens and only provide cross-sectional information from a single time point. There is a critical need to develop a noninvasive approach that would provide dynamic TAM response to radiation treatment. The overall objective in this application is to utilize a novel perfluorocarbons (PFC)-based nanoemulsion tracer and fluorine-19 (19F) magnetic resonance imaging (MRI) to noninvasively monitor TAM burden post radiation therapy. The central hypothesis is that the proposed imaging platform will enable longitudinal and spatial quantification of TAM infiltration in response to irradiation and provide noninvasive monitoring of TAM burden changes to different radiation treatment approaches.
Materials/Methods: We evaluated the capacity of PFC-based nanoemulsion and 19F MRI to monitor TAM infiltration in response to radiation therapy using groups of irradiated and control mice bearing orthotopic breast tumors. A small animal irradiator XRad-320 (Precision X-Ray, CT) was used to deliver focal irradiation. Two irradiated cohorts were established, receiving single-fraction doses of 5Gy and 20Gy, respectively. PFC-based nanoemulsion is injected via tail vein after irradiation. Molecular MRIs were collected on a small animal MRI (Bruker Scientific, MA) at 1 day and 7 days post irradiation. After imaging, tumors were harvested for pathological analyses.
Results: The imaging experiment showed no significant difference in TAM density between control and irradiated groups on day 1 post irradiation, but on day 7 irradiated group showed significantly higher TAM infiltration than control tumors (p = 0.0048). Group comparisons of longitudinal TAM density changes showed a statistically significant difference between day 1 and day 7 post irradiation for 5Gy irradiated tumors (p = 0.04). Multi-staining immunofluorescence images showed strong colocalization of molecular imaging PFC nanoemulsion probe and pan-macrophage histology marker F4/80.
Conclusion: This study develops a robust PFC 19F MRI monitoring system for radiation induced TAM detection and establishes quantitative evidence of how different radiation treatment strategies influence the macrophage landscape in tumors. This work is innovative because it is the first study to provide a dynamic in vivo dataset of TAM recruitment kinetics in responding to different clinical radiation treatment schemes. This study is significant because it represents an advancement of a clinically viable molecular imaging approach that provides individualized patient-specific tracking of TAM burden during radiation treatment.