Hyoxia imaging with ¹⁸F-fluoromisonidazole (FMISO) for differentiating tumors from granulomas: A comparison with FDG in experimental rat models using small animal PET

Objectives ¹⁸F-fluoromisonidazole (FMISO) is the most widely used for imaging tumor hypoxia. The degree of FMISO uptake is correlated with low tissue oxygen tension. Several experimental studies reported that areas of hypoxia are also present in chronic inflammations including granulomas, but the hypoxic conditions in the inflammations are different from that of tumors. Thus, we evaluated whether FMISO can be used for differentiating malignant tumors from granulomas in comparison with FDG using a small animal PET.

Methods Granuloma and tumor was established by inoculation with rhodococcus aurantiacus and glioma cells (C6) into the right and left calf muscles of rats (n=8), respectively. Three hours after injection of FMISO, FMISO PET scans were performed for 20 minutes using a small animal PET/CT system. Next day, FDG PET scans were also performed in the same rats at 60-80 minutes after injection of FDG. Then pimonidazole was intravenously injected at 60 minutes before sacrifice. FMISO and FDG uptakes were visually evaluated and quantified by calculating SUV and the lesion (tumor or granuloma) to background ratios. Immunohistochemical staining of pimonidazole (a hypoxia marker) in tumor and granuloma tissues was also performed to verify hypoxia status.

Results The tumors were clearly visualized by FMISO PET, but granulomas were negative. The mean SUV of FMISO in the tumor was 4.6 times of background, while that in the granuloma was background revel (tumor: 4.6 ± 1.2 vs. granuloma: 1.1 ± 0.1, p<0.001). SUVs of FDG uptake in the granuloma were similar to those in the tumor (p=ns). Positive staining for pimonidazole was observed in the tumor, but it was negative in the granuloma.

Conclusions The FMISO PET images clearly visualized the tumor but not the granuloma. Pimonidazole staining supported the hypoxia conditions of the lesions. Thus, FMISO PET may hold a promise for differentiating malignant tumors from granulomas, which deserves further elucidation