-
子宫内膜异位症(简称内异症)是指具有生长功能的子宫内膜组织出现在子宫以外部位的常见妇科疾病,约10%的育龄期女性患内异症[1],即全世界约有2亿女性患内异症。内异症主要的临床症状为腹痛、不孕和性交不适等,常发生于卵巢、子宫直肠陷凹和子宫骶韧带等部位,子宫内膜细胞还能通过淋巴和血管转移至盆腔外,该病有易复发、转移和浸润等特点。根据病变部位的不同,内异症分为腹膜型内异症(superficial peritoneal endometriosis,SPE)、卵巢子宫内膜异位囊肿(ovarian endometrioma,OMA)、深部浸润型内异症(deep infiltrating endometriosis,DIE)和其他类型内异症(包括切口处瘢痕内异症及肝脏、肺等部位的内异症)[2]。
目前内异症的诊断仍有很大挑战性,常规的腹腔镜、超声、MRI等检查对内异症的诊断具有重要意义,但其难以发现微小的、隐匿的内异症病灶[3-4]。腹腔镜对内异症的病灶范围、浸润深度以及深部病灶大小的诊断(尤其是在诊断存在子宫直肠陷凹封闭的DIE时)有一定局限性[5]。内异症的治疗包括手术切除和激素药物治疗,但未被发现的隐匿病灶常常导致术后复发,难以根治。故进一步寻找能够诊断微小的、隐匿的内异症病灶的新方法十分必要。
内异症相关基因的表达和调控异常使其常伴随炎症细胞浸润[6-7]、雌激素受体(estrogen receptor,ER)表达异常[8]、鞘磷脂和磷脂酰胆碱水平升高[9]、生长抑素受体(somatostatin receptor,SSTR)过表达[10]。针对以上靶点的分子探针有助于内异症的诊断,其能提供必要的分子信息,并指导临床治疗决策的制定。
-
有研究结果表明,部分内异症病灶明显摄取18F-FDG,这可能与内异症引起的炎症反应有关[6, 19]。然而,Fastrez等[7]对10例内异症患者行18F-FDG PET/CT,但未观察到任何高代谢的内异症病灶,故认为18F-FDG PET/CT在诊断内异症中的价值有限。另有研究结果表明,18F-FDG PET/CT可提示内异症的恶变[6, 20-21]。此外,Kusunoki等[22]通过18F-FDG PET/CT对31例外科怀疑为内异症恶变的患者进行鉴别,结果表明,SUVmax>4.0排除内异症的灵敏度为75%、特异度为100%、AUC=0.9。因此对于有内异症病史且出现临床症状的女性,在行18F-FDG PET/CT时应注意高代谢内异症病灶恶变的可能。
-
18F-氟代胆碱(fluorocholine,FCH)是一种胆碱类显像剂,其能在胆碱激酶过表达的细胞(如前列腺癌细胞、肺癌细胞等)中浓聚[23]。增殖细胞中胆碱激酶活性的升高会导致18F-FCH的高摄取[9]。胆碱在胆碱激酶的作用下可结合ATP生成磷脂酰胆碱。内异症的发生与鞘磷脂和卵磷脂水平的升高有关[9]。Silveira等[24]将成年雌性大鼠的自体子宫碎片移植至腹壁上,2周后行18F-FCH PET成功检出了内异症病灶,这表明18F-FCH PET具有诊断内异症的潜能;该机制可能与内异症引起的炎症反应有关,这也能解释为什么对照组大鼠移植的脂肪组织也对18F-FCH有轻度摄取。但随着时间推移,炎症浸润细胞可能会减少或消失[25],此时18F-FCHPET难以检出病灶,故18F-FCH PET可能并不适合诊断炎症反应较弱的内异症。
-
内异症病灶的增殖和进展与ER结合活性的升高及局部雌二醇生成过量有关[26]。16α-18F-17β-雌二醇(16α-[18F] fluoro-17β-estradiol,18F-FES)是一种雌激素类似物,其可以与ER结合。临床中18F-FES可用于乳腺癌[8, 27]、卵巢上皮性癌[28]的ER显像。有研究结果表明,乳腺癌原发灶和转移灶中18F-FES的摄取与ER的表达水平[8]及患者对激素治疗的反应[29]有良好的相关性。Tsuchida等[30]研究了子宫内膜和子宫肌层对18F-FES的摄取与月经周期或内源性雌激素水平的关系,发现增生期子宫内膜的SUV显著高于分泌期。
在Cosma等[31]的一项研究中,4例内异症患者已通过腹腔镜共探查了40个部位并进行活体组织病理学检查,研究者对患者行MRI和18F-FES PET/CT,并将结果与活体组织病理学检查结果比较,发现18F-FES PET/CT的诊断灵敏度为87.5%、特异度为100%;而MRI的诊断灵敏度仅为12.5%、特异度为90.6%;该研究中18F-FES PET/CT比MRI具有更高的诊断准确率,这可能与4例患者中有3例患者有腹部手术史有关。MRI相较于CT具有更高的软组织分辨率,在不考虑检查费用的情况下,PET/MRI可能更适合诊断内异症。ER和孕激素受体在各种类型的隐匿性内异症病灶中均有表达[3]。在内异症病灶充分摄取18F-FES的情况下,18F-FES PET/CT具有检出更加微小的、隐匿的内异症病灶的潜力,故可作为常规检查结果为阴性、腹盆腔手术后或盆腔组织结构紊乱且有临床症状的内异症患者的补充诊断方法,但这还需要更多的研究予以验证。同时,目前尚无应用18F-FES PET/CT预测激素治疗疗效的相关研究,未来可进一步探讨18F-FES摄取与激素治疗反应之间的关系。由于18F-FES经肠肝循环吸收,小肠吸收18F-FES后,大肠或乙状结肠的生理性摄取降低,因此18F-FES PET/CT对发生在大肠或乙状结肠的内异症的诊断可能具有一定优势。此外,18F-FES PET/CT应在患者月经周期的增生期进行,且患者在检查前应停用激素类药物[27]。
-
SSTR分为5种亚型,即SSTR1~5,其在多种神经内分泌肿瘤和神经系统肿瘤中过表达。SSTR在生长抑素的作用下可以抑制肿瘤细胞增殖、促进肿瘤细胞凋亡[32]。Green等[33]发现,SSTR2在正常的子宫内膜上皮、内皮和间质中均有表达,但表达水平差异很大,且随月经周期的变化不同。Fasciani等[10]发现,在OMA和SPE中SSTR1、SSTR2和SSTR5过表达,且与正常的子宫内膜相比,内异症病灶中SSTR1和SSTR2的表达水平升高了6倍。这些SSTR表达水平的升高可能与内异症的发生和发展有关。
生长抑素类似物(somatostatin analogs,SSTA)可与SSTR特异性结合,其主要由肾脏清除。目前常用的SSTA主要有第一代SSTA(奥曲肽、兰瑞肽)和第二代SSTA(帕瑞肽)[34],SSTA可与多种放射性核素合成显像剂。表1汇总了诊断内异症潜在的SSTA分子探针及其临床应用[10, 28, 34-38]。
放射性核素 半衰期/来源 成像方式 显像剂 作用受体 优点 缺点 68Ga 68 min/锗镓发生器 PET/CT、PET/MRI 68Ga-DOTA-TOC SSTR2、SSTR5 适用于神经内分泌肿瘤的诊断和分期,灵敏度高,可用于肽受体放射性核素治疗前的影像学评估 合成成本较高、产量低,不能进行延迟显像 68Ga-DOTA-TATE SSTR2 68Ga-DOTA-NOC SSTR2、SSTR3、SSTR5 68Ga-DOTA-帕瑞肽 SSTR1、SSTR2、SSTR3、SSTR5 111In 2.8 d/回旋加
速器SPECT、SPECT/CT 111In-DTPA-OCT
111In-喷曲肽SSTR2、SSTR5 临床应用最早的SSTR显像剂 半衰期长,图像空间的分辨率有限,肝脏生理性摄取高 64Cu 12.70 h/回旋加速器 PET/CT、PET/MRI 64Cu-DOTA-TATE SSTR2 图像的空间分辨率、检出率较高,安全性良好,药物制备及临床使用便捷 合成成本较高,临床应用有待进一步研究 99Tcm 6.02 h/钼锝发生器 SPECT、SPECT/CT 99Tcm-HYNIC-OCT/TOC SSTR2 99Tcm易获得、半衰期和射线能量合适、化学性质良好,是最佳的SPECT显像核素 假阴性率较高,图像的空间分辨率有限,肝脏生理性摄取较高,影响病灶的检出 注:PET为正电子发射断层显像术;CT为计算机体层摄影术;MRI为磁共振成像;SPECT为单光子发射计算机体层摄影术;DOTA为1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸;TOC为苯丙氨酸1-酪氨酸3-奥曲肽;TATE为D-苯丙氨酸1-酪氨酸3-苏氨酸8-奥曲肽;NOC为碘化钠3-奥曲肽;DTPA为二亚乙基三胺五乙酸;OCT为奥曲肽;HYNIC为联肼尼克酰胺;SSTR为生长抑素受体 表 1 诊断子宫内膜异位症潜在的生长抑素类似物分子探针及其临床应用
Table 1. Potential molecular imaging probes of somatostatin analogs in the diagnosis of endometriosis and their clinical application
68Ga的半衰期为68 min,68Ga标记的DOTA螯合的肽与111In相比,对SSTR2的亲和力高8倍,68Ga-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸-D-苯丙氨酸1-酪氨酸3-苏氨酸8-奥曲肽(68Ga-DOTA-D-Phe1-Tyr3-Thr8-octreotide,68Ga-DOTA-TATE)对SSTR2的亲和力高于68Ga-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸-苯丙氨酸1-酪氨酸3-奥曲肽(68Ga-DOTA-Phe1-Tyr3-octreotide,68Ga-DOTA-TOC)和68Ga-1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸-碘化钠3-奥曲肽(68Ga-DOTA-NaI3-octreotide,68Ga-DOTA-NOC)[36],68Ga-DOTA-NOC对SSTR3和SSTR5也具有较高的亲和力,68Ga-DOTA-TOC也可以与SSTR5结合(亲和力低于68Ga-DOTA-NOC)[37-38]。Fasciani等[10]通过对8例内异症患者行111In-喷曲肽SPECT成功检出了内异症病灶(其中6例患者的病灶信号较强,2例患者的病灶信号较弱),这表明SSTR显像可以用于内异症病灶的检出。Fastrez等[39]对12例疑似内异症的患者在行腹腔镜手术前行68Ga-DOTA-TATE PET/CT,并检测病灶中SSTR1、SSTR2和SSTR5的表达情况,发现有4个DIE病灶(其中2个在结肠、1个在直肠、1个在直肠阴道膈)和1个局灶性子宫腺肌症病灶的PET/CT结果为阳性;68Ga-DOTA-TATE PET/CT对DIE的诊断灵敏度仅为57%、特异度为80%。在所有SSTR2表达呈阳性的病灶中,其诊断灵敏度为80%、特异度为100%,这表明68Ga-DOTA-TATE PET/CT诊断内异症的准确率可能与内异症病灶是否表达SSTR2以及具体的表达程度有关。随后,Fastrez等[40]在一项纳入OMA、SPE和DIE患者各33例的研究中发现,SSTR2在后盆腔DIE、前盆腔DIE、SPE、OMA和结肠DIE中的表达阳性率分别为72.2%、37.5%、9.0%、16.6%和75.0%,这进一步表明SSTR2可能与后盆腔或结肠DIE的发生和发展密切相关,且68Ga-DOTA-TATE PET/CT可能更适合用于SSTR表达呈阳性的内异症的诊断。因此,对于存在临床常规检查无法检出的微小或隐匿(尤其是高表达SSTR2)的病灶,且高度怀疑为后盆腔或结肠DIE的患者,68Ga-DOTA-TATE PET/CT是一种值得尝试的新的诊断方法。表2汇总了经免疫组织化学检查或反转录PCR法分析的不同类型内异症中SSTR各亚型的表达情况[10, 40-41]。
SSTR亚型 卵巢子宫内膜
异位囊肿腹膜型内异症 深部浸润型内异症 无子宫内膜异位症
患者的正常子宫内膜子宫内膜异位症患者
同源的在位子宫内膜SSTR1 95.8 95.4 100 7.1 33.3 SSTR2 16.6 9.0 63.3 7.1 41.7 SSTR3 − − − 21.4 58.3 SSTR4 − − − 28.6 58.3 SSTR5 50.0~83.3 67.0~77.2 80.0 50.0~64.3 88.3 注:SSTR为生长抑素受体;−表示无此项内容 表 2 不同类型子宫内膜异位症中生长抑素受体各亚型的表达阳性率(%)
Table 2. The positive rate of expression of somatostatin receptor subtypes in different types of endometriosis (%)
子宫内膜异位症分子影像学诊断的研究进展
Research progress of molecular imaging diagnosis of endometriosis
-
摘要: 子宫内膜异位症(简称内异症)是常见的妇科疾病,在育龄期女性中的发病率较高,其发病部位广,通过常规影像学检查和腹腔镜无法有效检出全身的、微小的、隐匿的内异症病灶。放射性核素标记的胆碱类似物、雌激素类似物和生长抑素类似物等具有检出内异症病灶的潜能,并能够提供内异症病灶的功能和代谢信息,对内异症的诊断具有特殊价值。笔者就内异症的诊断方法进行综述,并探讨内异症分子影像学诊断的研究进展。
-
关键词:
- 子宫内膜异位症 /
- 正电子发射断层显像术 /
- 胆碱 /
- 受体,雌激素 /
- 受体,生长抑素
Abstract: Endometriosis is a common gynecological disease with a high incidence in women of childbearing age and has a wide range of sites in the body. Conventional imaging examinations and laparoscopy cannot effectively detect systemic, small and insidious endometriosis lesions. Radionuclide labeled choline analogs, estrogen analogs and somatostatin analogs have the potential to detect endometriosis lesions, and can provide functional and metabolic information of endometriosis lesions, which have special value for the diagnosis of endometriosis. In this paper, the diagnostic methods of endometriosis are reviewed, and the research progress of molecular imaging diagnosis of endometriosis is disscussed.-
Key words:
- Endometriosis /
- Positron-emission tomography /
- Choline /
- Receptors, estrogen /
- Receptors, somatostatin
-
表 1 诊断子宫内膜异位症潜在的生长抑素类似物分子探针及其临床应用
Table 1. Potential molecular imaging probes of somatostatin analogs in the diagnosis of endometriosis and their clinical application
放射性核素 半衰期/来源 成像方式 显像剂 作用受体 优点 缺点 68Ga 68 min/锗镓发生器 PET/CT、PET/MRI 68Ga-DOTA-TOC SSTR2、SSTR5 适用于神经内分泌肿瘤的诊断和分期,灵敏度高,可用于肽受体放射性核素治疗前的影像学评估 合成成本较高、产量低,不能进行延迟显像 68Ga-DOTA-TATE SSTR2 68Ga-DOTA-NOC SSTR2、SSTR3、SSTR5 68Ga-DOTA-帕瑞肽 SSTR1、SSTR2、SSTR3、SSTR5 111In 2.8 d/回旋加
速器SPECT、SPECT/CT 111In-DTPA-OCT
111In-喷曲肽SSTR2、SSTR5 临床应用最早的SSTR显像剂 半衰期长,图像空间的分辨率有限,肝脏生理性摄取高 64Cu 12.70 h/回旋加速器 PET/CT、PET/MRI 64Cu-DOTA-TATE SSTR2 图像的空间分辨率、检出率较高,安全性良好,药物制备及临床使用便捷 合成成本较高,临床应用有待进一步研究 99Tcm 6.02 h/钼锝发生器 SPECT、SPECT/CT 99Tcm-HYNIC-OCT/TOC SSTR2 99Tcm易获得、半衰期和射线能量合适、化学性质良好,是最佳的SPECT显像核素 假阴性率较高,图像的空间分辨率有限,肝脏生理性摄取较高,影响病灶的检出 注:PET为正电子发射断层显像术;CT为计算机体层摄影术;MRI为磁共振成像;SPECT为单光子发射计算机体层摄影术;DOTA为1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸;TOC为苯丙氨酸1-酪氨酸3-奥曲肽;TATE为D-苯丙氨酸1-酪氨酸3-苏氨酸8-奥曲肽;NOC为碘化钠3-奥曲肽;DTPA为二亚乙基三胺五乙酸;OCT为奥曲肽;HYNIC为联肼尼克酰胺;SSTR为生长抑素受体 表 2 不同类型子宫内膜异位症中生长抑素受体各亚型的表达阳性率(%)
Table 2. The positive rate of expression of somatostatin receptor subtypes in different types of endometriosis (%)
SSTR亚型 卵巢子宫内膜
异位囊肿腹膜型内异症 深部浸润型内异症 无子宫内膜异位症
患者的正常子宫内膜子宫内膜异位症患者
同源的在位子宫内膜SSTR1 95.8 95.4 100 7.1 33.3 SSTR2 16.6 9.0 63.3 7.1 41.7 SSTR3 − − − 21.4 58.3 SSTR4 − − − 28.6 58.3 SSTR5 50.0~83.3 67.0~77.2 80.0 50.0~64.3 88.3 注:SSTR为生长抑素受体;−表示无此项内容 -
[1] Shafrir AL, Farland LV, Shah DK, et al. Risk for and consequences of endometriosis: a critical epidemiologic review[J]. Best Pract Res Clin Obstet Gynaecol, 2018, 51: 1−15. DOI: 10.1016/j.bpobgyn.2018.06.001. [2] Zondervan KT, Becker CM, Missmer SA. Endometriosis[J]. N Engl J Med, 2020, 382(13): 1244−1256. DOI: 10.1056/NEJMra1810764. [3] Gubbels AL, Li R, Kreher D, et al. Prevalence of occult microscopic endometriosis in clinically negative peritoneum during laparoscopy for chronic pelvic pain[J]. Int J Gynaecol Obstet, 2020, 151(2): 260−266. DOI: 10.1002/ijgo.13303. [4] Roman H, Merlot B, Forestier D, et al. Nonvisualized palpable bowel endometriotic satellites[J]. Hum Reprod, 2021, 36(3): 656−665. DOI: 10.1093/humrep/deaa340. [5] 郑玉梅, 彭超, 陆叶, 等. 深部浸润型子宫内膜异位症在盆腔子宫内膜异位症中的发生率及其临床病理特征分析[J]. 中华妇产科杂志, 2020, 55(6): 384−389. DOI: 10.3760/cma.j.cn112141-20191202-00654.
Zheng YM, Peng C, Lu Y, et al. Incidence of deeply infiltrating endometriosis among 240 cases of pelvic endometriosis and analysis of its clinical and pathological characteristics[J]. Chin J Obstetr Gynecol, 2020, 55(6): 384−389. DOI: 10.3760/cma.j.cn112141-20191202-00654.[6] Mulette P, Jacquet A, Durlach A, et al. Pulmonary cavitations with increased 18F-FDG uptake revealing a thoracic endometriosis: a case report[J]. Medicine (Baltimore), 2021, 100(42): e27550. DOI: 10.1097/MD.0000000000027550. [7] Fastrez M, Nogarède C, Tondeur M, et al. Evaluation of 18FDG PET-CT in the diagnosis of endometriosis: a prospective study[J]. Reprod Sci, 2011, 18(6): 540−544. DOI: 10.1177/1933719110392060. [8] Peterson LM, Mankoff DA, Lawton T, et al. Quantitative imaging of estrogen receptor expression in breast cancer with PET and 18F-fluoroestradiol[J]. J Nucl Med, 2008, 49(3): 367−374. DOI: 10.2967/jnumed.107.047506. [9] Vouk K, Hevir N, Ribič-Pucelj M, et al. Discovery of phosphatidylcholines and sphingomyelins as biomarkers for ovarian endometriosis[J]. Hum Reprod, 2012, 27(10): 2955−2965. DOI: 10.1093/humrep/des152. [10] Fasciani A, Quilici P, Biscaldi E, et al. Overexpression and functional relevance of somatostatin receptor-1, -2, and -5 in endometrium and endometriotic lesions[J]. J Clin Endocrinol Metab, 2010, 95(12): 5315−5319. DOI: 10.1210/jc.2010-0397. [11] Guerriero S, Ajossa S, Pascual MA, et al. Ultrasonographic soft markers for detection of rectosigmoid deep endometriosis[J]. Ultrasound Obstet Gynecol, 2020, 55(2): 269−273. DOI: 10.1002/uog.20289. [12] Nisenblat V, Bossuyt PMM, Farquhar C, et al. Imaging modalities for the non-invasive diagnosis of endometriosis[J/OL]. Cochrane Database Syst Rev, 2016, 2(2): CD009591[2021-08-22]. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD009591.pub2/full. DOI: 10.1002/14651858.CD009591.pub2. [13] Guerra A, Daraï E, Osório F, et al. Imaging of postoperative endometriosis[J]. Diagn Interv Imaging, 2019, 100(10): 607−618. DOI: 10.1016/j.diii.2018.11.003. [14] Foti PV, Farina R, Palmucci S, et al. Endometriosis: clinical features, MR imaging findings and pathologic correlation[J]. Insights Imaging, 2018, 9(2): 149−172. DOI: 10.1007/s13244-017-0591-0. [15] Khan KS, Tryposkiadis K, Tirlapur SA, et al. MRI versus laparoscopy to diagnose the main causes of chronic pelvic pain in women: a test-accuracy study and economic evaluation[J]. Health Technol Assess, 2018, 22(40): 1−92. DOI: 10.3310/hta22400. [16] Lier MCI, Vlek SL, Ankersmit M, et al. Comparison of enhanced laparoscopic imaging techniques in endometriosis surgery: a diagnostic accuracy study[J]. Surg Endosc, 2020, 34(1): 96−104. DOI: 10.1007/s00464-019-06736-8. [17] Rauh-Hain JA, Laufer MR. Increased diagnostic accuracy of laparoscopy in endometriosis using indigo carmine: a new technique[J]. Fertil Steril, 2011, 95(3): 1113−1114. DOI: 10.1016/j.fertnstert.2010.12.017. [18] Mondal SB, O'Brien CM, Bishop K, et al. Repurposing molecular imaging and sensing for cancer image-guided surgery[J]. J Nucl Med, 2020, 61(8): 1113−1122. DOI: 10.2967/jnumed.118.220426. [19] Arsenault F, Turcotte É. Endometriosis under estradiol stimulation imaged using 18F-FDG and its control after estradiol cessation and progesterone hormonal replacement[J]. Clin Nucl Med, 2016, 41(3): e143−e145. DOI: 10.1097/RLU.0000000000001050. [20] Wang HY, Xue QY, Shou Y, et al. 18F-FDG simultaneous PET/MR findings of a malignant transformation and metastases of abdominal wall endometriosis[J]. Eur J Nucl Med Mol Imaging, 2020, 47(13): 3190−3191. DOI: 10.1007/s00259-020-04761-7. [21] Li NN, Zhou WX, Zhao L, et al. Endometriosis-associated recto-sigmoid cancer: a case report[J/OL]. BMC Cancer, 2018, 18(1): 905[2021-08-22]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6148997. DOI: 10.1186/s12885-018-4797-4. [22] Kusunoki S, Ota T, Kaneda H, et al. Analysis of positron emission tomography/computed tomography in patients to differentiate between malignant transformation of endometrioma and endometrioma[J]. Int J Clin Oncol, 2016, 21(6): 1136−1141. DOI: 10.1007/s10147-016-1013-x. [23] Roland A, Drouet C, Boulahdour H, et al. Unusual uptakes on 18F-fluorocholine positron emission tomography/computed tomography (PET/CT): a retrospective study of 368 prostate cancer patients referred for a biochemical recurrence or an initial staging[J]. Quant Imaging Med Surg, 2021, 11(1): 172−182. DOI: 10.21037/qims-19-981. [24] Silveira MB, Rodrigues DM, Araújo MR, et al. 18F-fluorocholine uptake and positron emission tomography imaging in rat peritoneal endometriosis[J]. Reprod Sci, 2018, 25(1): 19−25. DOI: 10.1177/1933719117728799. [25] Uchiide I, Ihara T, Sugamata M. Pathological evaluation of the rat endometriosis model[J]. Fertil Steril, 2002, 78(4): 782−786. DOI: 10.1016/s0015-0282(02)03327-7. [26] Tosti C, Biscione A, Morgante G, et al. Hormonal therapy for endometriosis: from molecular research to bedside[J]. Eur J Obstet Gynecol Reprod Biol, 2017, 209: 61−66. DOI: 10.1016/j.ejogrb.2016.05.032. [27] Sundararajan L, Linden HM, Link JM, et al. 18F-fluoroestradiol[J]. Semin Nucl Med, 2007, 37(6): 470−476. DOI: 10.1053/j.semnuclmed.2007.08.003. [28] van Kruchten M, de Vries EF, Arts HJ, 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. [29] Katzenellenbogen JA. The quest for improving the management of breast cancer by functional imaging: the discovery and development of 16α-[18F]fluoroestradiol (FES), a PET radiotracer for the estrogen receptor, a historical review[J]. Nucl Med Biol, 2021, 92: 24−37. DOI: 10.1016/j.nucmedbio.2020.02.007. [30] Tsuchida T, Okazawa H, Mori T, et al. In vivo imaging of estrogen receptor concentration in the endometrium and myometrium using FES PET-influence of menstrual cycle and endogenous estrogen level[J]. Nucl Med Biol, 2007, 34(2): 205−210. DOI: 10.1016/j.nucmedbio.2006.12.003. [31] Cosma S, Salgarello M, Ceccaroni M, et al. Accuracy of a new diagnostic tool in deep infiltrating endometriosis: positron emission tomography-computed tomography with 16α-[18F]fluoro-17β-estradiol[J]. J Obstet Gynaecol Res, 2016, 42(12): 1724−1733. DOI: 10.1111/jog.13117. [32] 冯柳, 吴爽, 金晨涛, 等. 生长抑素受体显像剂在神经内分泌肿瘤中的临床研究进展[J]. 国际放射医学核医学杂志, 2021, 45(6): 376−382. DOI: 10.3760/cma.j.cn121381-202102027-00043.
Feng L, Wu S, Jin CT, et al. Clinical research progress of somatostatin receptor imaging agents in neuroendocrine tumors[J]. Int J Radiat Med Nucl Med, 2021, 45(6): 376−382. DOI: 10.3760/cma.j.cn121381-202102027-00043.[33] Green VL, Richmond I, Maguiness S, et al. Somatostatin receptor 2 expression in the human endometrium through the menstrual cycle[J]. Clin Endocrinol, 2002, 56(5): 609−614. DOI: 10.1046/j.1365-2265.2002.01521.x. [34] Eychenne R, Bouvry C, Bourgeois M, et al. Overview of radiolabeled somatostatin analogs for cancer imaging and therapy[J/OL]. Molecules, 2020, 25(17): 4012[2021-08-22]. https://www.mdpi.com/1420-3049/25/17/4012. DOI: 10.3390/molecules25174012. [35] Pfeifer A, Knigge U, Binderup T, et al. 64Cu-DOTATATE PET for neuroendocrine tumors: a prospective head-to-head comparison with 111In-DTPA-octreotide in 112 patients[J]. J Nucl Med, 2015, 56(6): 847−854. DOI: 10.2967/jnumed.115.156539. [36] Ambrosini V, Nanni C, Fanti S. The use of gallium-68 labeled somatostatin receptors in PET/CT imaging[J]. PET Clin, 2014, 9(3): 323−329. DOI: 10.1016/j.cpet.2014.03.008. [37] Virgolini I, Ambrosini V, Bomanji JB, et al. Procedure guidelines for PET/CT tumour imaging with 68Ga-DOTA-conjugated peptides: 68Ga-DOTA-TOC, 68Ga-DOTA-NOC, 68Ga-DOTA-TATE[J]. Eur J Nucl Med Mol Imaging, 2010, 37(10): 2004−2010. DOI: 10.1007/s00259-010-1512-3. [38] Virgolini I, Gabriel M, Kroiss A, et al. Current knowledge on the sensitivity of the 68Ga-somatostatin receptor positron emission tomography and the SUVmax reference range for management of pancreatic neuroendocrine tumours[J]. Eur J Nucl Med Mol Imaging, 2016, 43(11): 2072−2083. DOI: 10.1007/s00259-016-3395-4. [39] Fastrez M, Artigas C, Sirtaine N, et al. Value of the 68Ga-DOTATATE PET-CT in the diagnosis of endometriosis. A pilot study[J]. Eur J Obstet Gynecol Reprod Biol, 2017, 212: 69−74. DOI: 10.1016/j.ejogrb.2017.03.022. [40] Fastrez M, Marchisello C, Rassy M, et al. Immunohistochemical analysis of somatostatin receptors in endometriosis tissue samples: a retrospective study[J]. Int J Gynecol Pathol, 2019, 38(4): 371−376. DOI: 10.1097/PGP.0000000000000522. [41] Zhao YH, Peng L, Li X, et al. Expression of somatostatin and its receptor 1−5 in endometriotic tissues and cells[J]. Exp Ther Med, 2018, 16(5): 3777−3784. DOI: 10.3892/etm.2018.6730.