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18F-fluoromisonidazole PET/CT: a potential tool for predicting primary endocrine therapy resistance in breast cancer
Jingyi Cheng1, Li Lei, Junyan Xu
1Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.
Unlabelled:
Although endocrine therapy is an effective method to treat estrogen receptor (ER)-positive breast cancer, approximately 30%-40% of all hormone receptor-positive tumors display de novo resistance. The aim of our current study was to analyze whether (18)F-labeled fluoromisonidazole (1-(2-nitro-1-imidazolyl)-2-hydroxy-3-fluoropropane [(18)F-FMISO]) PET/CT could predict primary resistance to hormonal therapy in ER-positive breast cancer.
Methods:
Postmenopausal women who had ER-α-positive breast cancer, stages II-IV, and had never received prior endocrine therapy were prospectively enrolled in this study. Patients underwent both (18)F-FDG and (18)F-FMISO PET/CT scans before and after treatment. The hottest (18)F-FDG standardized uptake value (SUV) in the tumor foci, the SUVs at 2 and 4 h, and the TBR2 h and TBR4 h for the target lesions were calculated (TBR2 h = SUV2 hT/SUV2 hB and TBR4 h = SUV4 hT/SUV4 hB [TBR is the tumor-to-background ratio]). Clinical outcomes of primary endocrine therapy with letrozole were evaluated according to the criteria of the World Health Organization after at least 3 mo of treatment. Immunohistochemistry for markers of proliferation (Ki67) and hypoxia-induced factor 1α was performed on a subset of tumors that had undergone biopsy or surgery. Pearson and Spearman analysis was used to determine the correlation between the parameters of (18)F-FDG and (18)F-FMISO uptake and clinical or immunohistochemistry outcomes with a 0.01 threshold for statistical significance.
Results:
A total of 45 lesions (13 primary, 32 metastatic) from 20 patients met the inclusion criteria in this study. Baseline (18)F-FDG and (18)F-FMISO PET/CT scans were obtained for 33 lesions from 16 patients. The correlation between baseline (18)F-FDG uptake and clinical outcome was weak and did not reach statistical significance (r = 0.37, P = 0.031). However, there was a significantly positive correlation between baseline (18)F-FMISO uptake (SUV2 hT, TBR2 h, SUV4 hT, and TBR4 h) and clinical outcomes after ≥3 mo of primary endocrine therapy with letrozole (r = 0.77, 0.76, 0.71, and 0.78, respectively; P < 0.0001). The application of a TBR4 h cutoff of ≥1.2 allowed the prediction of 88% of the cases of progressive disease (15/17). Despite poor correlation between (18)F-FMISO uptake and hypoxia-induced factor 1α expression, a marginal positive correlation between TBR4 h and Ki67 expression was measured (r = 0.51, P = 0.011) in a subset of malignant lesions acquired by biopsy or surgery.
Conclusion:
(18)F-FMISO PET/CT can be used to predict primary endocrine resistance in ER-positive breast cancer.
Insights
Fluoromisonidazole (18)F-FMISO PET/CT scans can predict primary resistance to endocrine therapy in estrogen receptor-positive breast cancer. This imaging technique accurately identifies patients likely to progress on hormonal treatment.
Area of Science:
- Oncology
- Nuclear Medicine
- Radiopharmaceuticals
Background:
- Endocrine therapy is a standard treatment for estrogen receptor (ER)-positive breast cancer.
- A significant portion (30-40%) of ER-positive tumors exhibit primary resistance to endocrine therapy.
- Predicting this resistance is crucial for optimizing patient treatment strategies.
Purpose of the Study:
- To evaluate the efficacy of (18)F-labeled fluoromisonidazole (18)F-FMISO positron emission tomography/computed tomography (PET/CT) in predicting primary resistance to hormonal therapy in ER-positive breast cancer.
- To correlate (18)F-FMISO uptake with clinical outcomes and proliferation markers.
Main Methods:
- Prospective enrollment of postmenopausal women with ER-α-positive breast cancer (stages II-IV) without prior endocrine therapy.
- Performance of (18)F-FDG and (18)F-FMISO PET/CT scans before and after treatment.
- Calculation of standardized uptake values (SUV) and tumor-to-background ratios (TBR) for (18)F-FMISO uptake.
- Correlation analysis between PET/CT parameters, clinical outcomes (WHO criteria), and immunohistochemistry (Ki67, HIF-1α).
Main Results:
- A strong positive correlation was observed between baseline (18)F-FMISO uptake (SUV and TBR) and clinical outcomes after letrozole therapy (r = 0.71-0.78, P < 0.0001).
- (18)F-FDG uptake showed a weak, non-significant correlation with clinical outcomes (r = 0.37, P = 0.031).
- A TBR4 h cutoff of ≥1.2 predicted progressive disease with 88% accuracy (15/17 cases). A marginal correlation between TBR4 h and Ki67 expression was noted (r = 0.51, P = 0.011).
Conclusions:
- (18)F-FMISO PET/CT is a valuable tool for predicting primary resistance to endocrine therapy in ER-positive breast cancer.
- This imaging modality can help identify patients unlikely to respond to hormonal treatment, guiding alternative therapeutic decisions.
