CD13作为前列腺特异性膜抗原阴性前列腺癌的潜在诊疗靶点及[F]AlF-CD13-L1 PET/CT成像的首例人体研究。
CD13 as a potential theranostic target for prostate-specific membrane antigen-negative prostate cancer and first-in-human study of [F]AlF-CD13-L1 PET/CT imaging.
作者信息
Tang Wei, Zhou Ming, Lu Chenxi, Qi Lin, Zhang Ye, Tang Yongxiang, Gao Xiaomei, Hu Shuo, Cai Yi
机构信息
Department of Urology, Disorders of Prostate Cancer Multidisciplinary Team, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Department of Nuclear Medicine, Disorders of Prostate Cancer Multidisciplinary Team, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
出版信息
Eur J Nucl Med Mol Imaging. 2025 Feb 22. doi: 10.1007/s00259-025-07140-2.
PURPOSE
Approximately 10% of prostate cancer (PCa) are prostate-specific membrane antigen (PSMA)-negative, leading to blind spots in PSMA-based diagnosis. This study aimed to identify a potential target for PSMA-negative PCa and preliminarily evaluate the feasibility of using radionuclide probe targeting the identified target for PCa diagnosis.
METHODS
Quantitative protein analysis was performed on eight PSMA-negative PCa and eleven controls to identify a potential molecular target, followed by validation with an expanded cohort using immunohistochemistry. Sixteen participants underwent [F]AlF-CD13-L1 PET/CT scanning, with the PCa pathological tissues used as references to interpret the imaging results.
RESULTS
Quantitative protein analysis revealed CD13 as the most significantly upregulated membrane protein in PSMA-negative PCa. Expanded validation results indicated that CD13 positivity rates were 92.9% (13/14), 82.7% (105/127), 91.7% (11/12), and 70% (14/20) in PSMA-negative PCa, PSMA-positive PCa, ductal adenocarcinoma of the prostate (DAC), and intraductal carcinoma of the prostate (IDC-P), respectively. In PCa participants, the median [F]AlF-CD13-L1 PET/CT maximum standardized uptake value (SUVmax) of tumors and tumor-to-muscle ratio were 4.3 (1.5-5.8) and 4.6 (1.7-6.1), respectively. The SUVmax value of the PCa lesions and the tumor-to-muscle ratio showed a positive correlation with the immunohistochemical score of CD13 of the PCa lesions (r = 0.6249, p = 0.025; r = 0.6714, p = 0.015, respectively), with CD13-positive tumors showing significant radiotracer accumulation.
CONCLUSION
CD13 was a potential target for PSMA-negative PCa and also showed high positivity rates in PSMA-positive PCa, DAC, and IDC-P. [F]AlF-CD13-L1 selectively accumulated in CD13-positive PCa, enabling visualization. (Trial registration: ChiCTR2300077817. Registered November 21, 2023).
目的
约10%的前列腺癌（PCa）为前列腺特异性膜抗原（PSMA）阴性，导致基于PSMA的诊断存在盲点。本研究旨在确定PSMA阴性PCa的潜在靶点，并初步评估使用靶向该靶点的放射性核素探针进行PCa诊断的可行性。
方法
对8例PSMA阴性PCa和11例对照进行定量蛋白质分析以确定潜在分子靶点，随后使用免疫组织化学在扩大队列中进行验证。16名参与者接受了[F]AlF-CD13-L1 PET/CT扫描，以PCa病理组织作为参考来解释成像结果。
结果
定量蛋白质分析显示CD13是PSMA阴性PCa中上调最显著的膜蛋白。扩大验证结果表明，PSMA阴性PCa、PSMA阳性PCa、前列腺导管腺癌（DAC）和前列腺导管内癌（IDC-P）中CD13阳性率分别为92.9%（13/14）、82.7%（105/127）、91.7%（11/12）和70%（14/20）。在PCa参与者中，肿瘤的[F]AlF-CD13-L1 PET/CT最大标准化摄取值（SUVmax）中位数和肿瘤与肌肉比值分别为4.3（1.5 - 5.8）和4.6（1.7 - 6.1）。PCa病变的SUVmax值和肿瘤与肌肉比值与PCa病变CD13免疫组化评分呈正相关（分别为r = 0.6249，p = 0.025；r = 0.6714，p = 0.015），CD13阳性肿瘤显示出明显的放射性示踪剂积聚。
结论
CD13是PSMA阴性PCa的潜在靶点，在PSMA阳性PCa、DAC和IDC-P中也显示出高阳性率。[F]AlF-CD13-L1选择性积聚在CD13阳性PCa中，实现可视化。（试验注册号：ChiCTR2300077817。于2023年11月21日注册）
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