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靶向生长抑素受体的神经内分泌肿瘤核素诊断与治疗

刘清杏 臧洁 任家坤 朱朝晖

刘清杏, 臧洁, 任家坤, 朱朝晖. 靶向生长抑素受体的神经内分泌肿瘤核素诊断与治疗[J]. 协和医学杂志, 2020, 11(4): 370-376. doi: 10.3969/j.issn.1674-9081.2020.04.003
引用本文: 刘清杏, 臧洁, 任家坤, 朱朝晖. 靶向生长抑素受体的神经内分泌肿瘤核素诊断与治疗[J]. 协和医学杂志, 2020, 11(4): 370-376. doi: 10.3969/j.issn.1674-9081.2020.04.003
Qing-xing LIU, Jie ZANG, Jia-kun REN, Zhao-hui ZHU. Radionuclide Imaging and Therapy of Neuroendocrine Neoplasm by Targeting the Somatostatin Receptor[J]. Medical Journal of Peking Union Medical College Hospital, 2020, 11(4): 370-376. doi: 10.3969/j.issn.1674-9081.2020.04.003
Citation: Qing-xing LIU, Jie ZANG, Jia-kun REN, Zhao-hui ZHU. Radionuclide Imaging and Therapy of Neuroendocrine Neoplasm by Targeting the Somatostatin Receptor[J]. Medical Journal of Peking Union Medical College Hospital, 2020, 11(4): 370-376. doi: 10.3969/j.issn.1674-9081.2020.04.003

靶向生长抑素受体的神经内分泌肿瘤核素诊断与治疗

doi: 10.3969/j.issn.1674-9081.2020.04.003
基金项目: 

国家自然科学基金 8187071730

中国医学科学院重大协同创新项目 2019-I2M-1-001

中国医学科学院临床与转化医学研究基金 2019XK320032

详细信息
    通讯作者:

    朱朝晖  电话:010-69154196, E-mail:13611093752@163.com

  • 中图分类号: R817

Radionuclide Imaging and Therapy of Neuroendocrine Neoplasm by Targeting the Somatostatin Receptor

More Information
  • 摘要: 神经内分泌肿瘤(neuroendocrine neoplasm, NEN)是以神经内分泌分化为主要特征的一组不同类型的肿瘤。多数NEN细胞表面有生长抑素受体(somatostatin receptor, SSTR)高表达, 为核医学分子影像诊断及多肽-受体介导的放射性核素治疗(peptide receptor radionuclide therapy, PRRT)提供了重要靶点。这一方向近年来已成为国内外的研究热点, 且临床转化和应用进展迅速, 不断出现新的突破。本文系统介绍靶向SSTR的核医学分子影像和PRRT治疗的现状与进展, 以及在NEN诊疗中的主要优势和重要价值, 为相关专业临床诊疗决策提供参考。
    利益冲突  无
  • 图  1  胰腺G2级NEN术后,肝脏多发转移灶的68Ga-DOTA-TATE PET/CT图像显示低剂量(15.5 mCi); 177Lu-DOTA-EB-TATE治疗前(A~C)与治疗后3个月(D~F)对比,病灶摄取明显减低(蓝色箭头所示病灶的SUVmax从82.4降至24.8,红色箭头所示病灶的SUVmax从34.9降至18.6),病灶看起来增大,可能是中心坏死所致

    NEN:神经内分泌肿瘤;PET/CT:正电子发射断层显像/计算机体层成像;SUVmax:最高标准摄取值

    图  2  177Lu-DOTA-EB-TATE与177Lu-DOTA-TATE在NEN患者中药代动力学比较A.177Lu-DOTA-EB-TATE摄取在第3次(72 h)测定时达最高,第5次(168 h)测定时SUV仍维持在高水平;B.177Lu-DOTA-TATE在第2次(3 h)测定时已达最高,第5次(72 h)测定时已降至很低,提示177Lu-DOTA-TATE经EB改构后,在肿瘤中的摄取显著增加

    NEN:同图 1;SUV:标准摄取值;EB:伊文思兰

    表  1  SSTR-RADS诊断分级[27]

    分级 具体标准 摄取水平 是否PRRT
    1级(非NEN) 确认非NEN(活检证实或常规影像有非NEN的典型表现)
       1A 病灶区域无示踪剂摄取 L1
       1B 局部有摄取(如前列腺炎、前列腺增生或甲状腺腺瘤等) L2~L3
    2级(可能非NEN) 非常见NEN转移部位的软组织病灶(如腋窝淋巴结);疑非NEN的骨病变
    (如强烈提示退行性骨病变的病灶)
    L1
    3级(不确定) 提示NEN,但不确定,需进一步活检或随访确认
       3A NEN软组织转移的好发部位(如局部淋巴结有可疑摄取) L1~L2
       3B NEN骨转移好发部位有可疑摄取 L1~L2 单病灶:否; 多病灶:是
       3C 在NEN的高度不好发部位出现了高放射性摄取灶(如乳腺摄取),通常需组
    织活检进一步确认
    L3
       3D 常规影像学高度怀疑NEN,但病灶无任何放射性摄取,推荐活检,18F-FDG
    PET/CT检查可能具有价值
    L1
    4级(高度疑为NEN) 在NEN典型、好发部位有放射性高摄取灶,但常规影像学上缺乏明确发现 L3 可考虑
    5级(几乎确认为NEN) 在NEN典型、好发部位有放射性高摄取灶,常规影像上有明确发现 L3
    SSTR-RADS:生长抑素受体报告和数据系统;PRRT:多肽-受体介导的放射性核素治疗;18F-FDG:18F-脱氧葡萄糖;PET/CT、NEN:同图 1
    下载: 导出CSV
  • [1] Kim JY, Hong SM, Ro JY, et al. Recent updates on grading and classification of neuroendocrine tumors[J]. Ann Diagn Pathol, 2017, 29:11-16. doi:  10.1016/j.anndiagpath.2017.04.005
    [2] 陈野野, 刘洪生, 李单青, 等.胸腺神经内分泌肿瘤手术治疗及预后因素[J].协和医学杂志, 2016, 7:190-194. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=xhyx201603006
    [3] Theodoropoulou M, Stalla GK. Somatostatin receptors:from signaling to clinical practice[J]. Front Neuroendocrinol, 2013, 34:228-252. doi:  10.1016/j.yfrne.2013.07.005
    [4] Lee ST, Kulkarni HR, Singh A, et al. Theranostics of neuroendocrine tumors[J]. Visc Med, 2017, 33:358-366. doi:  10.1159/000480383
    [5] Bombardieri E, Maccauro M, De Deckere E, et al. Nuclear medicine imaging of neuroendocrine tumours[J]. Ann Oncol, 2001, 12 Suppl 2:S51-S61. https://www.sciencedirect.com/science/article/pii/S0923753419544969
    [6] O'Toole D, Ducreux M, Bommelaer G, et al. Treatment of carcinoid syndrome:a prospective crossover evaluation of lanreotide versus octreotide in terms of efficacy, patient acceptability, and tolerance[J]. Cancer, 2000, 88:770-776. doi:  10.1002/(SICI)1097-0142(20000215)88:4<770::AID-CNCR6>3.0.CO;2-0
    [7] Tian R, Jacobson O, Niu G, et al. Evans blue attachment enhances somatostatin receptor subtype-2 imaging and radiotherapy[J]. Theranostics, 2018, 8:735-745. doi:  10.7150/thno.23491
    [8] Zhang J, Wang H, Jacobson O, et al. Safety, pharmacokinetics and dosimetry of a long-acting radiolabeled somatosta-tin analogue 177Lu-DOTA-EB-TATE in patients with advan-ced metastatic neuroendocrine tumors[J]. J Nucl Med, 2018, 59:1699-1705. doi:  10.2967/jnumed.118.209841
    [9] Fani M, Braun F, Waser B, et al. Unexpected sensitivity of sst2 antagonists to N-terminal radiometal modifications[J]. J Nucl Med, 2012, 53:1481-1489. doi:  10.2967/jnumed.112.102764
    [10] Ginj M, Zhang HW, Waser B, et al. Radiolabeled somatostatin receptor antagonists are preferable to agonists for in vivo peptide receptor targeting of tumors[J]. Proc Natl Acad Sci U S A, 2006, 103:16436-16441. doi:  10.1073/pnas.0607761103
    [11] Zhang J, Singh A, Kulkarni HR, et al. From bench to bedside-the Bad Berka experience with first-in-human studies[J]. Semin Nucl Med, 2019, 49:422-437. doi:  10.1053/j.semnuclmed.2019.06.002
    [12] Werner RA, Weich A, Kircher M, et al. The theranostic promise for neuroendocrine tumors in the late 2010s- where do we stand, where do we go?[J].Theranostics, 2018, 8:6088-6100. doi:  10.7150/thno.30357
    [13] Waldmann CM, Stuparu AD, van Dam RM, et al. The search for an alternative to[(68)Ga]Ga-DOTA-TATE in neuroendocrine tumor theranostics:current state of (18)F-labeled somatostatin analog development[J]. Theranostics, 2019, 9:1336-1347. doi:  10.7150/thno.31806
    [14] 谭思婷, 尹吉林, 王欣璐, 等. 64Cu标记生长抑素受体显像剂的研究进展[J].中国医学计算机成像杂志, 2015, 21:398-401. http://www.wanfangdata.com.cn/details/detail.do?_type=perio&id=zgyxjsjcx201504019
    [15] Hope TA, Bergsland EK, Bozkurt MF, et al. Appropriate use criteria for somatostatin receptor PET imaging in neuroendocrine tumors[J]. J Nucl Med, 2018, 59:66-74. doi:  10.2967/jnumed.117.202275
    [16] Imhof A, Brunner P, Marincek N, et al. Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue[90Y-DOTA]-TOC in metastasized neuroendocrine cancers[J]. J Clin Oncol, 2011, 29:2416-2423. doi:  10.1200/JCO.2010.33.7873
    [17] Kwekkeboom DJ, de Herder WW, Kam BL, et al. Treat-ment with the radiolabeled somatostatin analog[177Lu-DOTA 0, Tyr3]octreotate:toxicity, efficacy, and survival[J]. J Clin Oncol, 2008, 26:2124-2130. doi:  10.1200/JCO.2007.15.2553
    [18] Muller C, Reber J, Haller S, et al. Direct in vitro and in vivo comparison of 161Tb and 177Lu using a tumour-targeting folate conjugate[J]. Eur J Nucl Med Mol I, 2014, 41:476-485. doi:  10.1007/s00259-013-2563-z
    [19] Hindie E, Zanotti-Fregonara P, Quinto MA, et al. Dose deposits from 90Y, 177Lu, 111In, and 161Tb in micrometastases of various sizes:implications for radiopharmaceutical therapy[J]. J Nucl Med, 2016, 57:759-764. doi:  10.2967/jnumed.115.170423
    [20] Pomme S, Marouli M, Suliman G, et al. Measurement of the 225Ac half-life[J]. Appl Radiat Isot, 2012, 70:2608-2614. doi:  10.1016/j.apradiso.2012.07.014
    [21] Sgouros G, Roeske JC, McDevitt MR, et al. MIRD Pamphlet No. 22(abridged):radiobiology and dosimetry of alpha-particle emitters for targeted radionuclide therapy[J]. J Nucl Med, 2010, 51:311-328. doi:  10.2967/jnumed.108.058651
    [22] Kratochwil C, Giesel FL, Bruchertseifer F, et al. 213Bi-DOTATOC receptor-targeted alpha-radionuclide therapy induces remission in neuroendocrine tumours refractory to beta radiation:a first-in-human experience[J]. Eur J Nucl Med Mol I, 2014, 41:2106-2119. doi:  10.1007/s00259-014-2857-9
    [23] Haidar M, Shamseddine A, Panagiotidis E, et al.The role of 68Ga-DOTA-NOC PET/CT in evaluating neuroendocrine tu-mors:real-world experience from two large neuroendocrine tumor centers[J]. Nucl Med Commun, 2017, 38:170-177. doi:  10.1097/MNM.0000000000000623
    [24] Chen SH, Chang YC, Hwang TL, et al. 68Ga-DOTATOC and 18F-FDG PET/CT for identifying the primary lesions of suspected and metastatic neuroendocrine tumors:A prospective study in Taiwan[J]. J Formos Med Assoc, 2018, 117:480-487. doi:  10.1016/j.jfma.2017.07.007
    [25] Werner RA, Bundschuh RA, Bundschuh L, et al. Molecular imaging reporting and data systems (MI-RADS):a generalizable framework for targeted radiotracers with theranostic implications[J]. Ann Nucl Med, 2018, 32:512-522. doi:  10.1007/s12149-018-1291-7
    [26] Werner RA, Thackeray JT, Pomper MG, et al. Recent updates on molecular imaging reporting and data systems (MI-RADS) for theranostic radiotracers-navigating pitfalls of SSTR- and PSMA-targeted PET/CT[J]. J Clin Med, 2019, 8:1060. doi:  10.3390/jcm8071060
    [27] Werner RA, Solnes LB, Javadi MS, et al. SSTR-RADS version 1.0 as a reporting system for SSTR PET imaging and selection of potential PRRT candidates:a proposed standardization framework[J]. J Nucl Med, 2018, 59:1085-1091. doi:  10.2967/jnumed.117.206631
    [28] Dieter H, Samer E, Alexander H, et al. Effectiveness and side-effects of peptide receptor radionuclide therapy for neuroendocrine neoplasms in Germany:A multi-institutional registry study with prospective follow-up[J]. Eur J Cancer, 2016, 58:41-51. doi:  10.1016/j.ejca.2016.01.009
    [29] Baum R, Kulkarni H, Singh A, et al. Results and adverse events of personalized peptide receptor radionuclide therapy with 90Yttrium and 177Lutetium in 1048 patients with neuroendocrine neoplasms[J]. Oncotarget, 2018, 9:16932-16950. doi:  10.18632/oncotarget.24524
    [30] Kunikowska J, Pawlak D, Bak MI, et al. Long-term results and tolerability of tandem peptide receptor radionuclide therapy with 90Y/177Lu-DOTATATE in neuroendocrine tumors with respect to the primary location:a 10-year study[J]. Ann Nucl Med, 2017, 31:347-356. doi:  10.1007/s12149-017-1163-6
    [31] Claringbold PG, Brayshaw PA, Price RA, et al. Phase Ⅱ study of radiopeptide 177Lu-octreotate and capecitabine therapy of progressive disseminated neuroendocrine tumours[J]. Eur J Nucl Med Mol I, 2011, 38:302-311. doi:  10.1007/s00259-010-1631-x
    [32] Claringbold PG, Price RA, Turner JH, et al. Phase Ⅰ-Ⅱ study of radiopeptide 177Lu-octreotate in combination with capecitabine and temozolomide in advanced low-grade neuroendocrine tumors[J]. Cancer Biother Radiopharm, 2012, 27:561-569. doi:  10.1089/cbr.2012.1276
    [33] Kesavan M, Claringbold PG, Turner JH, et al. Hemato-logical toxicity of combined 177Lu-octreotate radiopeptide chemotherapy of gastroenteropancreatic neuroendocrine tumors in long-term follow-up[J]. Neuroendocrinology, 2014, 99:108-117. doi:  10.1159/000362558
    [34] Claringbold PG, Turner JH. Pancreatic neuroendocrine tu-mor control:durable objective response to combination 177Lu-octreotatecapecitabine-temozolomide radiopeptide chemo-therapy[J]. Neuroendocrinology, 2016, 103:432-439. doi:  10.1159/000434723
    [35] Claringbold PG, Turner JH. NeuroEndocrine Tumor Therapy with Lutetium-177-octreotate and Everolimus (NETTLE):a phase I study[J]. Cancer Biother Radiopharm, 2015, 30:261-269. doi:  10.1089/cbr.2015.1876
    [36] McStay MK, Maudgil D, Williams M, et al. Large-volume liver metastases from neuroendocrine tumors:hepatic intraarterial 90Y-DOTA-lanreotide as effective palliative therapy[J]. Radiology, 2005, 237:718-726. doi:  10.1148/radiol.2372041203
    [37] Chan DL, Pavlakis N, Schembri GP, et al. Dual somatos-tatin receptor/FDG PET/CT imaging in metastatic neuroendocrine tumours:proposal for a novel grading scheme with prognostic significance[J]. Theranostics, 2017, 7:1149-1158. doi:  10.7150/thno.18068
    [38] Bozkurt MF, Virgolini I, Balogova S, et al. Guideline for PET/CT imaging of neuroendocrine neoplasms with 68Ga-DOTA-conjugated somatostatin receptor targeting peptides and 18F-DOPA[J]. Eur J Nucl Med Mol I, 2017, 44:1588-1601. doi:  10.1007/s00259-017-3728-y
    [39] Strosberg J, El-Haddad G, Wolin E, et al. Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors[J]. N Engl J Med, 2017, 376:125-135. doi:  10.1056/NEJMoa1607427
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  • 收稿日期:  2020-04-10
  • 刊出日期:  2020-07-30

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