The specification and use of 18F-FES PET in breast cancer

doi:10.19401/j.cnki.1007-3639.2023.08.009

Abstract

Abstract:

Estrogen receptor (ER) is overexpressed in approximately 2/3 of breast cancer patients’ lesions. Noninvasive detection of ER in vivo and dynamic monitoring of ER are crucial for individualized treatment decision-making. 16α-¹⁸F-17β-fluoroestradiol (¹⁸F-FES) positron emission tomography (PET) has been used in a variety of preclinical and clinical studies to detect ER expression. However, there is still a lack of technical specifications in China. This technical specification was jointly written by domestic experts who had experience of ¹⁸F-FES PET imaging and was formed through consultation based on their own experience and research progress in this field both domestically and internationally. This technical specification introduced the synthesis method and quality control requirements of ¹⁸F-FES, recommended its clinical application scenarios, and classified them. In addition, experts’ suggestions were provided throughout the entire process systemically and detailly, including pre-imaging preparation, imaging process, image analysis (normal biological distribution, determination of ER positive and negative, lesion detection, influencing factors, false negative and false positive, report requirements), and the limitations of this imaging technique were proposed. The future application prospects were also discussed. This specification aimed to promote the standardized application of ¹⁸F-FES PET in China, achieve repeatability and comparability, and provide important molecular imaging technical support for accurate diagnosis and treatment of breast cancer.

Key words: Breast cancer, Positron emission tomography, 16α-¹⁸F-17β-fluoroestradiol, Specification, Application

CLC Number:

R737.9

YANG Zhongyi, XU Xiaoping, WANG Mingwei, ZHANG Yongping, YANG Jianwei, CHEN Yue, XU Wengui, LI Yaming, ZHANG Yingjian, SONG Shaoli. The specification and use of ¹⁸F-FES PET in breast cancer[J]. China Oncology, 2023, 33(8): 801-808.

Figures/Tables 5

References 41

[1]	QIU H, CAO S, XU R. Cancer incidence, mortality, and burden in China: a time-trend analysis and comparison with the United States and United Kingdom based on the global epidemiological data released in 2020[J]. Cancer Commun (Lond), 2021, 41(10): 1037-1048.
[2]	HAYES D F, DOWSETT M, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer[J]. J Clin Oncol, 2010, 28(16): 2784-2795. doi: 10.1200/JCO.2009.25.6529 pmid: 20404251
[3]	KALINOWSKI L, SAUNUS J M, MCCART REED A E, et al. Breast cancer heterogeneity in primary and metastatic disease[J]. Adv Exp Med Biol, 2019, 1152: 75-104. doi: 10.1007/978-3-030-20301-6_6 pmid: 31456181
[4]	KIESEWETTER D O, KILBOURN M R, LANDVATTER S W, et al. Preparation of four fluorine-18-labeled estrogens and their selective uptakes in target tissues of immature rats[J]. J Nucl Med, 1984, 25(11): 1212-1221.
[5]	ULANER G A. 16α-18F-fluoro-17β-fluoroestradiol (FES): clinical applications for patients with breast cancer[J]. Semin Nucl Med, 2022, 52(5): 574-583. doi: 10.1053/j.semnuclmed.2022.03.002 pmid: 35379454
[6]	MORI T, KASAMATSU S, MOSDZIANOWSKI C, et al. Automatic synthesis of 16 alpha-[(18)F]fluoro-17beta-estradiol using a cassette-type [(18)F]fluorodeoxyglucose synthesizer[J]. Nucl Med Biol, 2006, 33(2): 281-286. pmid: 16546684
[7]	张勇平, 章英剑, 王明伟, 等. 基于Explora GN/LC双模块的16α-[¹⁸F]氟-17β-雌二醇全自动化合成[J]. 中华核医学杂志, 2011, 31(3): 196-200.
	ZHANG Y P, ZHANG Y J, WANG M W, et al. Fully automated synthesis of 16α-[¹⁸F] fluoro-17B-estrogen using Explora GN/LC dual module[J]. Chin J Nucl Med, 2011, 31(3): 196-200.
[8]	袁慧瑜, 许晓平, 张勇平, 等. ¹⁸F-雌二醇的质量控制研究[J]. 肿瘤影像学 2015, 24(3): 190-195.
	YUAN H Y, XU X P, ZHANG Y P, et al. Quality control of ¹⁸F-fluoroestradiol for positron emission tomography[J]. Oncoradiology, 2015, 24(3): 190-195.
[9]	YANG Z Y, YUAN H Y, XU X P, et al. High specific activity is not optimal: ¹⁸F-fluoroestradio positron emission tomography-computed tomography results in a breast cancer xenograft[J]. J Label Compd Radiopharm, 2016, 59(13): 576-581. doi: 10.1002/jlcr.v59.13
[10]	YANG Z, SUN Y, XU X, et al. The assessment of estrogen receptor status and its intratumoral heterogeneity in patients with breast cancer by using ¹⁸F-fluoroestradiol PET/CT[J]. Clin Nucl Med, 2017, 42(6): 421-427. doi: 10.1097/RLU.0000000000001587
[11]	VAN GEEL J J L, BOERS J, ELIAS S G, et al. Clinical validity of 16α-[¹⁸F]fluoro-17β-estradiol positron emission tomography/computed tomography to assess estrogen receptor status in newly diagnosed metastatic breast cancer[J]. J Clin Oncol, 2022, 40(31): 3642-3652. doi: 10.1200/JCO.22.00400
[12]	KURLAND B F, WIGGINS J R, COCHE A, et al. Whole-body characterization of estrogen receptor status in metastatic breast cancer with 16α-¹⁸F-fluoro-17β-estradiol positron emission tomography: meta-analysis and recommendations for integration into clinical applications[J]. Oncologist, 2020, 25(10): 835-844. doi: 10.1634/theoncologist.2019-0967
[13]	CHAE S Y, AHN S H, KIM S B, et al. Diagnostic accuracy and safety of 16α-[¹⁸F]fluoro-17β-oestradiol PET-CT for the assessment of oestrogen receptor status in recurrent or metastatic lesions in patients with breast cancer: a prospective cohort study[J]. Lancet Oncol, 2019, 20(4): 546-555. doi: 10.1016/S1470-2045(18)30936-7
[14]	LIU C, GONG C C, LIU S, et al. ¹⁸F-FES PET/CT influences the staging and management of patients with newly diagnosed estrogen receptor-positive breast cancer: a retrospective comparative study with ¹⁸F-FDG PET/CT[J]. Oncologist, 2019, 24(12): e1277-e1285.
[15]	BOERS J, LOUDINI N, BRUNSCH C L, et al. Value of ¹⁸F-FES PET in solving clinical dilemmas in breast cancer patients: a retrospective study[J]. J Nucl Med, 2021, 62(9): 1214-1220. doi: 10.2967/jnumed.120.256826
[16]	ULANER G A, JHAVERI K, CHANDARLAPATY S, et al. Head-to-head evaluation of ¹⁸F-FES and ¹⁸F-FDG PET/CT in metastatic invasive lobular breast cancer[J]. J Nucl Med, 2021, 62(3): 326-331. doi: 10.2967/jnumed.120.247882
[17]	YANG Z Y XIE, Y Z, LIU C, et al. The clinical value of ¹⁸F-fluoroestradiol in assisting individualized treatment decision in dual primary malignancies[J]. Quant Imaging Med Surg, 2021, 11 (9), 3956-3965. doi: 10.21037/qims
[18]	VAN KRUCHTEN M, GLAUDEMANS A W J M, DE VRIES E F J, et al. PET imaging of estrogen receptors as a diagnostic tool for breast cancer patients presenting with a clinical dilemma[J]. J Nucl Med, 2012, 53(2): 182-190. doi: 10.2967/jnumed.111.092734
[19]	LIU C, HU S, XU X, et al. Evaluation of tumour heterogeneity by ¹⁸F-fluoroestradiol PET as a predictive measure in breast cancer patients receiving palbociclib combined with endocrine treatment[J]. Breast Cancer Res, 2022, 24(1): 57. doi: 10.1186/s13058-022-01555-7
[20]	XIE Y, DU X, ZHAO Y, et al. Chemotherapy shows a better efficacy than endocrine therapy in metastatic breast cancer patients with a heterogeneous estrogen receptor expression assessed by ¹⁸F-FES PET[J]. Cancers (Basel), 2022, 14(14): 3531. doi: 10.3390/cancers14143531
[21]	LIU C, XU X, YUAN H, et al. Dual tracers of 16α-[¹⁸F]fluoro-17β-estradiol and [¹⁸F]fluorodeoxyglucose for prediction of progression-free survival after fulvestrant therapy in patients with HR⁺/HER2^- metastatic breast cancer[J]. Front Oncol, 2020, 10: 580277. doi: 10.3389/fonc.2020.580277
[22]	HE M, LIU C, SHI Q, et al. The predictive value of early changes in ¹⁸F-fluoroestradiol positron emission tomography/computed tomography during fulvestrant 500 mg therapy in patients with estrogen receptor-positive metastatic breast cancer[J]. Oncol, 2020, 25(11): 927-936. doi: 10.1634/theoncologist.2019-0561
[23]	GONG C C, YANG Z Y, SUN Y F, et al. A preliminary study of ¹⁸F-FES PET/CT in predicting metastatic breast cancer in patients receiving docetaxel or fulvestrant with docetaxel[J]. Sci Rep, 2017, 7: 6584. doi: 10.1038/s41598-017-06903-8
[24]	VAN KRUCHTEN M, DE VRIES E G, GLAUDEMANS A W, et al. Measuring residual estrogen receptor availability during fulvestrant therapy in patients with metastatic breast cancer[J]. Cancer Discov, 2015, 5(1): 72-81. doi: 10.1158/2159-8290.CD-14-0697 pmid: 25380844
[25]	WANG Y B, AYRES K L, GOLDMAN D A, et al. ¹⁸F-fluoroestradiol PET/CT measurement of estrogen receptor suppression during a phase Ⅰ trial of the novel estrogen receptor-targeted therapeutic GDC-0810: using an imaging biomarker to guide drug dosage in subsequent trials[J]. Clin Cancer Res, 2017, 23(12): 3053-3060. doi: 10.1158/1078-0432.CCR-16-2197
[26]	LIN F I, GONZALEZ E M, KUMMAR S, et al. Utility of ¹⁸F-fluoroestradiol (¹⁸F-FES) PET/CT imaging as a pharmacodynamic marker in patients with refractory estrogen receptor-positive solid tumors receiving Z-endoxifen therapy[J]. Eur J Nucl Med Mol Imaging, 2017, 44(3): 500-508. doi: 10.1007/s00259-016-3561-8
[27]	JAGER A, DE VRIES E G E, DER HOUVEN VAN OORDT C W M, et al. A phase 1b study evaluating the effect of elacestrant treatment on estrogen receptor availability and estradiol binding to the estrogen receptor in metastatic breast cancer lesions using ¹⁸F-FES PET/CT imaging[J]. Breast Cancer Res, 2020, 22(1): 97. doi: 10.1186/s13058-020-01333-3
[28]	IQBAL R, YAQUB M, OPREA-LAGER D E, et al. Biodistribution of ¹⁸F-FES in patients with metastatic ER⁺ breast cancer undergoing treatment with rintodestrant (G1T48), a novel selective ER degrader[J]. J Nucl Med, 2022, 63(5): 694-699.
[29]	VENEMA C M, APOLLONIO G, HOSPERS G A, et al. Recommendations and technical aspects of 16α-[¹⁸F]fluoro-17β-estradiol PET to image the estrogen receptor in vivo: the groningen experience[J]. Clin Nucl Med, 2016, 41(11): 844-851. doi: 10.1097/RLU.0000000000001347
[30]	YOSHIDA Y, KIYONO Y, TSUJIKAWA T, et al. Additional value of 16α-[¹⁸F]fluoro-17β-oestradiol PET for differential diagnosis between uterine sarcoma and leiomyoma in patients with positive or equivocal findings on[¹⁸F]fluorodeoxyglucose PET[J]. Eur J Nucl Med Mol Imaging, 2011, 38(10): 1824-1831. doi: 10.1007/s00259-011-1851-8
[31]	VAN KRUCHTEN M, DE VRIES E F, ARTS H J, et al. Assessment of estrogen receptor expression in epithelial ovarian cancer patients using 16α-¹⁸F-fluoro-17β-estradiol PET/CT[J]. J Nucl Med, 2015, 56(1): 50-55. doi: 10.2967/jnumed.114.147579
[32]	ZHAO Z, YOSHIDA Y, KUROKAWA T, et al. ¹⁸F-FES and ¹⁸F-FDG PET for differential diagnosis and quantitative evaluation of mesenchymal uterine tumors: correlation with immunohistochemical analysis[J]. J Nucl Med, 2013, 54(4): 499-506. doi: 10.2967/jnumed.112.113472
[33]	BOELLAARD R, DELGADO-BOLTON R, OYEN W J G, et al. FDG PET/CT: EANM procedure guidelines for tumour imaging: version 2.0[J]. Eur J Nucl Med Mol Imaging, 2015, 42(2): 328-354. doi: 10.1007/s00259-014-2961-x
[34]	张建平, 何思敏, 顾丙新, 等. 基于小鼠全身动态PET扫描估算16α-¹⁸F-17β-雌二醇的人体内辐射剂量[J]. 中国癌症杂志, 2016, 26(9): 770-776. doi: 10.19401/j.cnki.1007-3639.2016.09.008
	ZHANG J P, HE S M, GU B X, et al. Radiation dosimetry estimates of ¹⁸F-fluoroestradiol based on whole-body PET imaging of mice[J]. China Oncol, 2016, 26(9): 770-776.
[35]	IQBAL R, MENKE-VAN DER HOUVEN VAN OORDT C W, OPREA-LAGER D E, et al. ¹⁸F-FES uptake in the pituitary gland and white matter of the brain[J]. Eur J Nucl Med Mol Imaging, 2021, 48(9): 3009-3010. doi: 10.1007/s00259-021-05281-8
[36]	BOERS J, LOUDINI N, DE HAAS R J, et al. Analyzing the estrogen receptor status of liver metastases with [¹⁸F]-FES-PET in patients with breast cancer[J]. Diagnostics (Basel), 2021, 11(11): 2019.
[37]	PETERSON L M, KURLAND B F, LINK J M, et al. Factors influencing the uptake of ¹⁸F-fluoroestradiol in patients with estrogen receptor positive breast cancer[J]. Nucl Med Biol, 2011, 38(7): 969-978. doi: 10.1016/j.nucmedbio.2011.03.002
[38]	YANG Z Y, SUN Y F, YAO Z F, et al. Increased ¹⁸F-fluoroestradiol uptake in radiation pneumonia[J]. Ann Nucl Med, 2013, 27(10): 931-934. doi: 10.1007/s12149-013-0761-1
[39]	DEHDASHTI F, MORTIMER J E, SIEGEL B A, et al. Positron tomographic assessment of estrogen receptors in breast cancer: comparison with FDG-PET and in vitro receptor assays[J]. J Nucl Med, 1995, 36(10): 1766-1774.
[40]	GEMIGNANI M L, PATIL S, SESHAN V E, et al. Feasibility and predictability of perioperative PET and estrogen receptor ligand in patients with invasive breast cancer[J]. J Nucl Med, 2013, 54(10): 1697-1702. doi: 10.2967/jnumed.112.113373
[41]	MCGUIRE A H, DEHDASHTI F, SIEGEL B A, et al. Positron tomographic assessment of 16 alpha-[¹⁸F]fluoro-17 beta-estradiol uptake in metastatic breast carcinoma[J]. J Nucl Med, 1991, 32(8): 1526-1531.

推荐内容	推荐水平	证据水平
诊断和分期
活体内评估病灶ER表达，尤其是难以活检的部位^{[10⇓⇓-13]}	I	A
对活组织病理学检查已明确为ER阳性的乳腺癌，¹⁸F-FES PET有望提高诊断和分期的准确性，尤其是对于传统影像学手段或¹⁸F-FDG无法明确性质的病灶^[14⇓-16]	Ⅱa	B
临床治疗决策指导
双原发肿瘤转移来源的辅助诊断^[15,17]	Ⅱb	C
病灶良恶性辅助定性^[18]	Ⅱb	C
疗效预测
通过ER异质性和（或）治疗前后变化的动态观察，可用于氟维司群、CDK4/6抑制剂等药物早期疗效预测^{[5,19⇓⇓⇓ -23]}	Ⅱa	B
药代动力学研究
基于治疗前后ER表达差异进行新药疗效学观察，为临床剂量爬坡提供定量依据^{[24⇓⇓⇓-28]}	Ⅱa	C

体重（kg）	注射剂量
体重（kg）	100-150 MBq	>150 MBq
0-60	2 min	1 min
60-90	4 min	2 min
>90	6 min	3 min

The specification and use of ¹⁸F-FES PET in breast cancer

RichHTML

PDF

Knowledge

Abstract

Cite this article

share this article

Figures/Tables 5

References 41

Related Articles 15

Recommended Articles

Metrics

Comments

[1]	XU Rui, WANG Zehao, WU Jiong. Advances in the role of tumor-associated neutrophils in the development of breast cancer [J]. China Oncology, 2024, 34(9): 881-889.
[2]	CAO Xiaoshan, YANG Beibei, CONG Binbin, LIU Hong. The progress of treatment for brain metastases of triple-negative breast cancer [J]. China Oncology, 2024, 34(8): 777-784.
[3]	ZHANG Jian. Clinical consideration of two key questions in assessing menopausal status of female breast cancer patients [J]. China Oncology, 2024, 34(7): 619-627.
[4]	JIANG Dan, SONG Guoqing, WANG Xiaodan. Study on the mechanism of mitochondrial dysfunction and CPT1A/ERK signal transduction pathway regulating malignant behavior in breast cancer [J]. China Oncology, 2024, 34(7): 650-658.
[5]	PAN Jian, YE Dingwei, ZHU Yao, WANG Beihe. Correlation analysis of PSMA PET/CT-derived parameters and circulating tumor DNA features in patients with hormone-sensitive prostate cancer [J]. China Oncology, 2024, 34(7): 680-685.
[6]	DONG Jianqiao, LI Kunyan, LI Jing, WANG Bin, WANG Yanhong, JIA Hongyan. A study on mechanism of SIRT3 inducing endocrine drug resistance in breast cancer via deacetylating YME1L1 [J]. China Oncology, 2024, 34(6): 537-547.
[7]	HAO Xian, HUANG Jianjun, YANG Wenxiu, LIU Jinting, ZHANG Junhong, LUO Yubei, LI Qing, WANG Dahong, GAO Yuwei, TAN Fuyun, BO Li, ZHENG Yu, WANG Rong, FENG Jianglong, LI Jing, ZHAO Chunhua, DOU Xiaowei. Establishment of primary breast cancer cell line as new model for drug screening and basic research [J]. China Oncology, 2024, 34(6): 561-570.
[8]	Committee of Breast Cancer Society, China Anti-Cancer Association. Expert consensus on clinical applications of ovarian function suppression for Chinese women with early breast cancer (2024 edition) [J]. China Oncology, 2024, 34(3): 316-333.
[9]	ZHANG Qi, XIU Bingqiu, WU Jiong. Progress of important clinical research of breast cancer in China in 2023 [J]. China Oncology, 2024, 34(2): 135-142.
[10]	ZHANG Siyuan, JIANG Zefei. Important research progress in clinical practice for advanced breast cancer in 2023 [J]. China Oncology, 2024, 34(2): 143-150.
[11]	WANG Zhaobu, LI Xing, YU Xinmiao, JIN Feng. Important research progress in clinical practice for early breast cancer in 2023 [J]. China Oncology, 2024, 34(2): 151-160.
[12]	LUO Yang, SUN Tao, SHAO Zhimin, CUI Jiuwei, PAN Yueyin, ZHANG Qingyuan, CHENG Ying, LI huiping, YANG Yan, YE Changsheng, YU Guohua, WANG Jingfen, LIU Yunjiang, LIU Xinlan, ZHOU Yuhong, BAI Yuju, GU Yuanting, WANG Xiaojia, XU Binghe, SONG Lihua. Efficacy, metabolic characteristics, safety and immunogenicity of AK-HER2 compared with reference trastuzumab in patients with metastatic HER2-positive breast cancer: a multicenter, randomized, double-blind phase Ⅲ equivalence trial [J]. China Oncology, 2024, 34(2): 161-175.
[13]	CHEN Yuanxiang, YU Tao, YANG Shiyu, ZENG Tao, WEI Lan, ZHANG Yan. KDM4A promotes the migration and invasion of breast cancer cell line MDA-MB-231 by downregulating BMP9 [J]. China Oncology, 2024, 34(2): 176-184.
[14]	HU Xiaoyu, CAI Yuwen, YE Fugui, SHAO Zhimin, HU Weigang, YU Keda. Impact of BRCA1/2 germline mutation on the incidence of second primary cancer following postoperative radiotherapy in patients with triple-negative breast cancer [J]. China Oncology, 2024, 34(2): 185-190.
[15]	ZHANG Siwei, MA Ding, JIANG Yizhou, SHAO Zhimin. “Subtype-precise” therapy leads diagnostic and therapeutic innovations: a new pattern for precision treatment of breast cancer [J]. China Oncology, 2024, 34(11): 1045-1052.