177Lu-PSMA靶向治疗转移性去势抵抗性前列腺癌的研究进展

赵艳红 陈跃

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177Lu-PSMA靶向治疗转移性去势抵抗性前列腺癌的研究进展

    通讯作者: 陈跃, chenyue5523@126.com

Progress in radioligand therapy with 177Lu-PSMA for the treatment of metastatic castration-resistant prostate cancer

    Corresponding author: Yue Chen, chenyue5523@126.com
  • 摘要: 前列腺癌是男性最常见的恶性肿瘤之一,尽管现有的治疗方法对多数前列腺癌患者可取得较好疗效,但对转移性去势抵抗性前列腺癌的治疗仍然极具挑战性,迫切需要发展更有效的治疗方法。目前,177Lu标记的前列腺特异性膜抗原靶向治疗是最有希望的新疗法之一,有望成为前列腺癌的标准治疗方案之一,该疗法安全、有效,可延长患者的总体生存期。
  • 图 1  前列腺特异性膜抗原结构示意图

    Figure 1.  Schematic diagram of prostate specific membrane antigen

    图 2  前列腺特异性膜抗原-617结构式

    Figure 2.  Chemical structure formula of prostate specific membrane antigen-617

    图 3  前列腺特异性膜抗原I&T结构式

    Figure 3.  Chemical structure formula of prostate specific membrane antigen I&T

    表 1  前列腺癌治疗相关性前列腺特异性膜抗原配体的特点

    Table 1.  Characteristics of prostate specific membrane antigen ligands associated with prostate cancer treatment

    生物学性质 配体名称 常用可标记核素 结合部位 特点
    单克隆抗体(鼠源性) 7E11(CYT356、
    CYT5400)
    177Lu、90Y、111In、99Tcm89Zr等 胞内域 单克隆抗体显像剂固有局限性;仅与PSMA表型阳性的坏死细胞结合,具有人鼠抗体反应
    单克隆抗体(鼠源性、人源性) J591 177Lu、90Y、213Bi、111In、89Zr、等 胞外域 单克隆抗体显像剂固有局限性;允许靶向活的、完整的肿瘤细胞
    PSMA的小分子抑制剂 PSMA-617
    (DOTA偶联)
    177Lu、90Y、213Bi、225Ac、131I、68Ga、111In、64Cu、44Sc等 胞外域 PSMA-11的变异体,具有PSMA-11的特性,并进一步改善药代动力学,增强肿瘤摄取并减少肾脏示踪剂聚集。177Lu-PSMA-617体内、体外稳定性好。
    PSMA小分子抑制剂 PSMA-I&T
    (DOTAGA偶联)
    177Lu、90Y、131I、68Ga、64Cu等 胞外域 与PAMA-617相似。但与177Lu-PSMA-617相比,全身摄取较低,半衰期较短,肾脏摄取略高、排泄较慢。标记步骤繁琐
    PSMA小分子配体 MIP-1095、MIP-1072 123I、124I、131I等 胞外域 肿瘤病变中迅速、高摄取并长时间滞留,肾脏摄取较高
     注:表中,PSMA为前列腺特异性膜抗原。
    下载: 导出CSV

    表 2  177Lu-前列腺特异性膜抗原治疗转移性去势抵抗性前列腺癌的疗效

    Table 2.  Therapeutic effect of 177Lu-prostate specific membrane antigen on metastatic castration resistant prostate cancer

    作者 例数 中位年龄(岁) 配体 中位剂量(GBq) PSA下降频率(%) PSA降>50%的频率(%)
    Rahbar[10] 145 73 617 5.9 60、66①、72② 45、40①、57②、65③④
    Rathke[22] 40 617 4.0、6.0、7.4、9.3 四组分别为:90、70、70、80 四组分别为:40、30、50、30
    Kulkarni[23] 119 617、I&T 6.0 76 58
    Rahbar[24] 104 70 617 6.1 67①②③④ 33
    Fendler[28] 15 73 617 3.7、6.0 80 47
    Kratochwil[30] 30 73 617 70① 43①
    Yadav[32] 31 66 617 5.1 71
    Rahbar[33] 28 73 617 59①、75② 32①、50②
    Rahbar[34] 82 73 617 5.9 64 31
    Rahbar[35] 71 72 617 6.0 66 56
    Ahmadzadehfar[36] 52 71 617 81①、73③ 44①、60③
    Ferdinandus[40] 40 71 617 6.0 68 33
    Bräuer[41] 59 72 617 6.1 91 53
    Ahmadzadehfar[42] 100 617 6.0 69 38
    Ahmadzadehfar[45] 49 617 67 53
    Ahmadzadehfar[46] 10 74 617 5.6 70 50
     注:表中,①、②、③、④分别表示:第一、二、三、四个治疗周期后;−:无此项数据。
    下载: 导出CSV

    表 3  177Lu-前列腺特异性膜抗原治疗转移性去势抵抗性前列腺癌的不良反应

    Table 3.  Adverse reactions of 177Lu-prostate specific membrane antigen in the treatment of metastatic castration resistant prostate cancer

    总例数 3/4级血液学毒性 口腔干燥症(%) 非血液学毒性
    血红蛋白(%) 白细胞(%) 血小板(%)
    Rahbar[10] 145 10 3 4 8 轻至中度恶心
    Kulkarni[23] 119 3.4 4.2 疲劳
    Yadav[32] 31 3.2 0 0
    Rahbar[33] 28 11 0 0 14 轻度恶心
    Rahbar[34] 82 2.8 0 0 8.5 轻度恶心
    Hofman[37] 30 0 0 13 87 轻度恶心、疲劳
    Bräuer[41] 59 19 3 3 25 恶心、腹泻、疲劳
    Ahmadzadehfar[45] 49 8.2 0 6.1
    Ahmadzadehfar[46] 10 10 0 0 0 轻度恶心、疲劳
    Ahmadzadehfar[47] 24 9 0 0 8.7 轻度恶心、疲劳
    Yordanova[48] 55 0 0 0
     注:表中,−:无此项数据或内容。
    下载: 导出CSV
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