期刊论文详细信息
Journal of Nuclear Medicine
18F-Fluoromisonidazole PET/CT: A Potential Tool for Predicting Primary Endocrine Therapy Resistance in Breast Cancer
Zhimin Shao1  Yifei Sun1  Lingling Pan1  Jingyi Cheng1  Xincun Wang1  Yongping Zhang1  Junyan Xu1  Guangyu Liu1  Li Lei1  Yingjian Zhang1 
关键词: hypoxia;    breast cancer;    18F-FMISO;    hormonal therapy;    resistance;   
DOI  :  10.2967/jnumed.112.111963
学科分类:医学(综合)
来源: Society of Nuclear Medicine
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【 摘 要 】

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 18F-labeled fluoromisonidazole (1-(2-nitro-1-imidazolyl)-2-hydroxy-3-fluoropropane [18F-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 18F-FDG and 18F-FMISO PET/CT scans before and after treatment. The hottest 18F-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 18F-FDG and 18F-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 18F-FDG and 18F-FMISO PET/CT scans were obtained for 33 lesions from 16 patients. The correlation between baseline 18F-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 18F-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 18F-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: 18F-FMISO PET/CT can be used to predict primary endocrine resistance in ER-positive breast cancer.

【 授权许可】

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