MR Signal Changes in Superparamagnetic Iron Oxide Nanoparticle‐labeled Macrophages in Response to X Irradiation

To investigate whether MR signals associated with macrophages labeled with superparamagnetic iron oxide nanoparticles (SPIONs) change in response to X irradiation, we performed in vitro MRI of SPION‐labeled macrophage‐like J774A.1 cells that were subsequently X irradiated. We labeled the cells with ferucarbotran at a concentration of 10 μg iron/mL in culture medium for 16 h and subsequently performed X irradiation at doses of 0, 2, 10, or 20 Gy using a low‐energy X‐ray unit. On Days 3 and 6, we suspended the cells in agar at a concentration of 2 × 106 cells/mL and acquired multi‐gradient echo and multi‐spin echo images of the cell samples using a 3 T scanner to estimate R2* and R2. In addition, we microscopically investigated the relationship among the MR signal changes, intracellular SPIONs, and acidic organelles. Our data showed that X irradiation of labeled cells caused increased SPION deposition in lysosomes compared with the non‐irradiated control. On Day 3, R2* and R2 values in the 0 to 10 Gy irradiated samples were dose‐dependently increased 5.4‐ and 1.5‐fold compared with 17 ± 2 and 13 ± 1/s, respectively, in the non‐irradiated control; these values plateaued at more than 10 Gy. Although the increases in R2*, R2, and SPION deposition were still observed in the 10 and 20 Gy samples on Days 6 and 7, the 2 Gy samples showed recovery in these parameters as cell growth was restored. Acidic organelles were temporarily increased in the irradiated cells, which suggests that the reduction in lysosomal acidity was not attributable to SPION deposition. In conclusion, X irradiation of macrophages can cause SPION deposition and R2* and R2 elevation in a specific dose range. MRI of SPION‐labeled and subsequently X‐irradiated macrophages may be utilized as a novel technique for investigating macrophage responses to X irradiation.