Micro PET imaging of 18F-Fluoromisonidazole in an MDA-MB-231 triple negative human breast cancer xenograft model

Abstract

Background: While 18 F-Fluoromisonidazole ( 18 F-FMISO) is the most frequently used positron emission tomography (PET) tracer for detecting hypoxia, it has not been studied in a metastatic triple-negative [lack expression of estrogen receptor (ER), progesterone receptor (PR) and human EGF receptor 2 (HER2)] human breast cancer cell xenografts model to our best knowledge. This study focuses on whether 18 F-FMISO can detect the hypoxic status of triple-negative human breast cancer (TNBC). Methods: The TNBC cells MDA-MB-231 were successfully inoculated in right forelimb of nude mice. Nude mice models with TNBC xenografts were assessed by micro-PET imaging with 18 F-FMISO, and hypoxic status of the TNBC xenografts was determined by immunohistochemistry. We also compared 18 F-FDG uptake, the most commonly used PET tracer in clinical practice, with 18 F-FMISO uptake to find out its correlation in MDA-MB-231 xenografts. Results: For 18 F-FMISO, intestines and liver as well as bladder could be seen in micro-PET images. 18 F-FDG showed physiologically high uptake in brain, heart, bladder and intestinal tracts. The quantitative radioactivity of 18 F-FMISO and 18 F-FDG in tumor were 2.18±0.15 and 3.84±0.54 %ID/g, respectively. The quantitative radioactivity of 18 F-FMISO and 18 F-FDG in muscle were 1.23±0.08 and 0.59±0.09 %ID/g, respectively. The tumor-to-muscle ratios were 1.79±0.015 and 7.11±2.84 for 18 F-FMISO and 18 F-FDG, respectively. Immunofluorescent images from MDA-MB-231 cryosections showed significant hypoxia. Conclusions: 18 F-FMISO PET may be used for detection of hypoxia in tumor microenvironment of triple negative human breast cancer.