In Vivo Imaging of Methionine Aminopeptidase II for Prostate Cancer Risk Stratification.
In Vivo Imaging of Methionine Aminopeptidase II for Prostate Cancer Risk Stratification.
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DOI：
10.1158/0008-5472.can-20-2969
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发表时间：
2021-05-01
期刊：
影响因子：
11.2
通讯作者：
Rao J
中科院分区：
文献类型：
--
作者：
Xie J;Rice MA;Chen Z;Cheng Y;Hsu EC;Chen M;Song G;Cui L;Zhou K;Castillo JB;Zhang CA;Shen B;Chin FT;Kunder CA;Brooks JD;Stoyanova T;Rao J
前列腺癌是世界上最常见的恶性肿瘤之一，但用于该疾病预后风险分层的工具有限。鉴定代表恶性转化内在特征的新生物标志物和发展预后成像技术对于改善治疗决策和患者生存至关重要。在这项研究中，我们分析了 422 名局部疾病患者的根治性前列腺切除术标本，以确定蛋氨酸氨肽酶 II (MetAP2) 的表达模式，蛋氨酸氨肽酶 II (MetAP2) 是一种胞质金属蛋白酶，已被确定为癌症的药物靶点。 MetAP2 在 54% 的低级别癌症和 59% 的高级别癌症中高表达。诊断时 MetAP2 水平升高与复发时间缩短相关。合成小分子的受控自组装能够设计出第一个 MetAP2 激活的正电子发射断层扫描 (PET) 成像示踪剂，用于监测体内 MetAP2 活性。 MetAP2 激活后组装的纳米颗粒在单个前列腺癌细胞中通过点击后荧光标记进行成像。通过微型 PET/CT 扫描，氟 18 标记的示踪剂成功区分了 MetAP2 敲除和抑制剂处理的人前列腺癌异种移植物中的 MetAP2 活性。这种高灵敏度的成像技术可能为前列腺癌的无创早期风险分层和监测MetAP2抑制剂作为抗癌药物的治疗效果提供新工具。
Prostate cancer is one of the most common malignancies worldwide, yet limited tools exist for prognostic risk stratification of the disease. Identification of new biomarkers representing intrinsic features of malignant transformation and development of prognostic imaging technologies are critical for improving treatment decisions and patient survival. In this study, we analyzed radical prostatectomy specimens from 422 patients with localized disease to define the expression pattern of methionine aminopeptidase II (MetAP2), a cytosolic metalloprotease that has been identified as a druggable target in cancer. MetAP2 was highly expressed in 54% of low-grade and 59% of high-grade cancer. Elevated levels of MetAP2 at diagnosis were associated with shorter time to recurrence. Controlled self-assembly of a synthetic small molecule enabled design of the first MetAP2-activated positron emission tomography (PET) imaging tracer for monitoring MetAP2 activity in vivo. The nanoparticles assembled upon MetAP2 activation were imaged in single prostate cancer cells with post-click fluorescent labeling. The fluorine-18 labeled tracers successfully differentiated MetAP2 activity in both MetAP2 knockdown and inhibitor-treated human prostate cancer xenografts by micro-PET/CT scanning. This highly sensitive imaging technology may provide a new tool for non-invasive early risk stratification of prostate cancer and monitoring the therapeutic effect of MetAP2 inhibitors as anti-cancer drugs.