USPIO-labeling nei macrofagi M1 e M2: studio in vitro con risonanza magnetica

Purpose: Tumor-associated macrophages (TAM) are recruited to the tumor site and programmed by tumor-derived factors in tumor-supportive M2-polarized macrophages, although M1-polarized TAM with anti-tumor activity have been described in several types of cancer. Aim of the present study was to evaluate if ultrasmall superparamagnetic iron oxide (USPIO) magnetic resonance (MR) could be used to depict distinct population of macrophages. Materials and Methods: Human monocytic cell line THP-1 were differentiated into macrophages using PMA and polarized according to the Tjiu method. A control population of macrophages, was developed from THP-1 cells with PMA (M0 macrophages). M1-polarized, M2-polarized and the M0 were incubated with USPIO research prototype (P904, CheMatech, Guerbet Research)(200 μg Fe/mL) for 36 hours. A M0 without P904 was the control non-treated population. M0, M0+P904, M1+P904 and M2+P904 were analyzed in gel phantoms containing at least 1x106 cells/milliliter with a 3.0T MR scan (Discovery MR750). Optical and electron microscopy was used as gold standard to evaluate the iron uptake. Results: M2+P904 showed a much greater T1 signal compared to the other population (p<0.0001), and the T2* signal was significantly lower compared to the other groups (p<0.0001); the R* was significantly higher for the M2+ P904 compared to the other populations (p<0.0001). Hystological analysis demonstrated higher iron content in the M2+P904 as compared to both the M1+904 (p=0.04) and the M0+P904 population (p=0.003). Ultrastructure analysis with a electron microscope demonstrated ubiquitous localization of P904 within the cellular compartments. Those results were confirmed with human macrophages. Conclusion: Avid and selective USPIO-labeling for M2-like population was demonstrated with a 3.0T clinical scan. Clinical relevance: USPIO-RM is able to depict M2 macrophage population. Further studies on same topic would be highly desirable to investigate the possible role of non-invasive diagnosis in inflammation and cancer imaging.