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中国癌症杂志 ›› 2016, Vol. 26 ›› Issue (7): 608-615.doi: 10.19401/j.cnki.1007-3639.2016.07.008

• 论著 • 上一篇    下一篇

99mTc标记PSMA小分子抑制剂靶向前列腺癌分子影像初步临床研究

胡四龙1,2,3,4，许晓平1,2,3,4，朱　耀5，宿恒川5，叶定伟5，姚之丰1,2,3,4，潘禾戎1,2,3,4，郭小毛3,4,6，章英剑1,2,3,4   

  1. 1. 复旦大学附属肿瘤医院核医学科，复旦大学上海医学院肿瘤学系，上海 200032 ；
    2. 复旦大学生物医学影像研究中心，上海 200032
    3. 上海分子影像探针工程技术研究中心( 筹)，上海 200032 ；
    4. 复旦大学附属肿瘤医院质子重离子中心，上海 201315 ；
    5. 复旦大学附属肿瘤医院泌尿外科，复旦大学上海医学院肿瘤学系，上海 200032 ；
    6. 复旦大学附属肿瘤医院放疗科，复旦大学上海医学院肿瘤学系，上海 200032
  • 出版日期:2016-07-30 发布日期:2016-08-22
  • 通信作者: 章英剑　E-mail: yjzhang111@aliyun.com
  • 基金资助:
    上海市科委项目(14DZ2251400)；上海市卫生和计划生育委员会项目(20124189)。

Preliminary clinical study of 99mTc-labelled small molecules against PSMA for prostate cancer imaging

HU Silong1,2,3,4, XU Xiaoping1,2,3,4, ZHU Yao5, SU Hengchuan5, YE Dingwei5, YAO Zhifeng1,2,3,4, PAN Herong1,2,3,4, GUO Xiaomao3,4,6, ZHANG Yingjian1,2,3,4   

  1. 1. Department of Nuclear Medicine, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; 2. Center for Biomedical Imaging, Fudan University, Shanghai 200032, China; 3. Shanghai Engineering Research Center for Molecular Imaging Probes, Shanghai 200032, China; 4. The Proton and Heavy Ion Center of Fudan University Shanghai Cancer Center, Shanghai 201315, China; 5. Department of Urology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; 6. Department of Radiotherapy, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China
  • Published:2016-07-30 Online:2016-08-22
  • Contact: ZHANG Yingjian E-mail: yjzhang111@aliyun.com

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摘要： 背景与目的：前列腺特异性膜抗原(prostate-specific membrane antigen，PSMA)在前列腺癌细胞表面特异性高表达，是前列腺癌诊断和治疗的极具有吸引力的靶点。放射性核素标记的PSMA小分子抑制剂能够高效、特异性探测前列腺癌病灶并进行分期。本研究初步探讨99mTc标记PSMA小分子抑制剂(HYNIC-Glu-Urea-A，简称99mTc-PSMA)SPECT/CT显像诊断前列腺原发灶和转移灶的价值。方法：24例前列腺癌和1例前列腺增生患者静脉注射99mTc-PSMA 2 h后行全身平面扫描和腹盆部SPECT/CT断层显像，采用感兴趣区技术计算肿瘤和肌肉摄取99mTc-PSMA比值(T/N)进行半定量分析，评价全身平面显像结合断层显像检测前列腺癌原发灶和(或)转移灶的灵敏度和特异度，分析99mTc-PSMA阳性率与前列腺癌特异性抗原(prostate-specific antigen，PSA)水平和Gleason评分的关系。结果：以患者为单位，99mTc-PSMA SPECT/CT对前列腺癌原发灶或转移灶检测的灵敏度为72.7%(16/22)、特异度为100%(3/3)。99mTc-PSMA阳性患者，(中位数17.31 ng/mL，范围2.26~3 239.00 ng/mL)水平明显高于99mTc-PSMA阴性患者PSA(中位数0.49 ng/mL，范围0.07~9.28 ng/mL)(Z=-3.51，P<0.001)；在初诊和PSA大于2 ng/mL的复发患者中，99mTc-PSMA阳性率明显提高，灵敏度达94.1%(16/17)；99mTc-PSMA的阳性率与Gleason评分高低无关(Z=-0.69，P=0.52)。结论：99mTc-PSMA全身平面显像结合局部SPECT/CT断层显像对前列腺癌原发灶和转移灶的探测有较高应用价值，灵敏度及特异度均较高。

关键词: 前列腺癌, 前列腺特异性膜抗原, 前列腺特异性抗原, Gleason评分, 99mTc-PSMA显像

Abstract: Background and purpose: Prostate-specific membrane antigen (PSMA), a cell surface protein with high expression in prostate carcinoma (PC) cells, is an attractive target for PC imaging and therapy. Small-molecule radiopharmaceuticals targeting PSMA can detect the location and extent of disease with high sensitivity and specificity. The aim of this study was to evaluate the value of technetium-99m-labelled small molecule against PSMA (HYNICGlu- Urea-A, 99mTc-PSMA) for the detection of primary and metastatic prostate cancers. Methods: Twenty-four prostate cancer patients and 1 patient with benign prostate hyperplasia received whole-body scan followed by abdominopelvic SPECT/CT 2 h after intravenous injection of 99mTc-PSMA. Tumor to muscle uptake ratio of 99mTc-PSMA was calculated using region of interest (ROI) technology. The sensitivity and specificity of 99mTc-PSMA were evaluated. The relationships between positive 99mTc-PSMA and prostate specific antigen (PSA) level and Gleason Score were analyzed. Results: Based on per patient, the sensitivity and specificity of 99mTc-PSMA were 72.7% (16/22) and 100% (3/3), respectively. The level of PSA in patients with positive 99mTc-PSMA imaging was significantly higher than that in patients with negative 99mTc-PSMA imaging [(PSA median 17.31 ng/mL, range: 2.26-3 239.0 ng/mL) vs (PSA median 0.49 ng/ mL, range: 0.07-9.28 ng/mL)] (Z=-3.51, P<0.001). Among newly diagnosed patients and recurrent patients with PSA more than 2.0 nm/mL, it was apparent that 99mTc-PSMA imaging was able to detect lesions with improved sensitivity of 94.1% (16/17). Gleason Scores between positive 99mTc-PSMA patients and negative 99mTc-PSMA patients were not significantly different (Z=-0.69, P=0.52). Conclusion: With the combination of whole-body scan and tomography, 99mTc-PSMA SPECT/CT can be an excellent and specific molecular imaging strategy to detect prostate cancer and its metastases.

Key words: Prostate cancer, Prostate-specific membrane antigen, Prostate-specific antigen, Gleason Score, 99mTc-PSMA imaging

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