Quantitative detection of macrophage activation in osteosarcoma comparing ¹⁸F-FDG PET/CT with ferumoxytol-enhanced...

Targeting CD47 with monoclonal antibody (mAb) therapy activates tumor-associated macrophages (TAMs). Quantitative imaging methods are important for identifying responders to this novel immunotherapy. The purpose of our study was to investigate whether the metabolic activity of osteosarcomas on ¹⁸F-FDG PET/CT changes after CD47 mAb treatment. Twenty female BALB/c mice with intratibial murine K7M2 osteosarcomas, twenty female NOD scid gamma (NSG) mice with intratibial human 143B tumors, and twenty male NSG mice with intratibial human MG63.3 tumors were treated with either phosphate-buffered saline (PBS) or murine/human CD47 mAb (n = 10 per arm) and underwent either ¹⁸F-FDG PET/CT or ferumoxytol-enhanced MRI (n = 5 per group). Differences in tumor metabolic activity (%ID/g max), tumor T2* relaxation times, TAM (%F4/80), and M1 macrophage polarization (%CD80⁺) between PBS and CD47 mAb-treated mice were estimated from linear regression. The tumor %ID/g max of CD47 mAb-treated K7M2 tumors (6.58 ± 2.42) was not significantly different compared to PBS-treated K7M2 tumors (8.04 ± 2.91; p = 0.17). Similarly, the tumor %ID/g max of CD47 mAb-treated 143B tumors (9.12 ± 1.68) and MG63.3 tumors (5.44 ± 1.99) were not significantly different compared to PBS-treated 143B tumors (9.38 ±  2.32; p = 0.32 ) and MG63.3 tumors (6.02 ±  0.63, p = 0.79 ). By comparison, K7M2 tumors, 143B tumors, and MG63.3 tumors all demonstrated significantly shorter T2* relaxation times after CD47 mAb treatment compared to PBS treatment (all p < 0.001). All tumors exhibited significantly higher TAM (%F4/80⁺) and M1 macrophage polarization (%CD80⁺) after CD47 mAb treatment compared to PBS treatment (all p < 0.05). The metabolic activity of osteosarcomas on ¹⁸F-FDG PET/CT does not show significant changes after CD47 mAb treatment. This lowers the risk of observing pseudoprogression and misinterpreting drug-induced inflammation, simplifying routine clinical scan interpretation.