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

摘要

Background and purpose:Prostate-speciifc 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 speciifcity. The aim of this study was to evaluate the value of technetium-99m-labelled small molecule against PSMA (HYNIC-Glu-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 of99mTc-PSMA. Tumor to muscle uptake ratio of99mTc-PSMA was calcu-lated using region of interest (ROI) technology. The sensitivity and specificity of99mTc-PSMA were evaluated. The relationships between positive99mTc-PSMA and prostate speciifc antigen (PSA) level and Gleason Score were analyzed. Results:Based on per patient, the sensitivity and speciifcity of99mTc-PSMA were 72.7% (16/22) and 100% (3/3), re-spectively. The level of PSA in patients with positive99mTc-PSMA imaging was signiifcantly higher than that in patients with negative99mTc-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 that99mTc-PSMA imaging was able to detect lesions with improved sensitivity of 94.1% (16/17). Gleason Scores between positive99mTc-PSMA patients and negative99mTc-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 speciifc molecular imaging strategy to detect prostate cancer and its metastases.%背景与目的：前列腺特异性膜抗原(prostate-speciifc 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-speciifc 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2.26~3239.00 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。