18F-fluoromisonidazole PET reveals spatial and temporal heterogeneity of hypoxia in mouse models of human non-small-cell lung cancer

Abstract

Aim: To noninvasively observe dynamic changes in tumor hypoxia in mouse models of human non-small-cell lung cancer (NSCLC) using 18F-fluoromisonidazole PET. Materials & methods: Nude mice with NSCLC H460 and A549 subcutaneous xenografts were coinjected intravenously with 18F-fluoromisonidazole and the hypoxia marker pimonidazole, and observed by serial PET scans. After sacrifice, the tumor distribution of 18F-fluoromisonidazole and pimonidazole was compared by digital autoradiography and microscopy, respectively. Results: The NSCLC hypoxic microenvironment was spatially heterogeneous. Serial PET scans over 48 h revealed an apparent change in the intratumoral distribution of 18F-fluoromisonidazole. Conclusion: The tumor hypoxic microenvironment is spatially and temporally heterogeneous, and hypoxic cancer cells have a shorter life span when growing in vivo. Therefore, the concept of hypoxic resistance and hypoxia-targeting therapy of macroscopic tumors should be revisited.