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Purpose <p>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.</p> Methods <p>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 [<sup>18</sup>F]AlF-CD13-L1 PET/CT scanning, with the PCa pathological tissues used as references to interpret the imaging results.</p> Results <p>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 [<sup>18</sup>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<sub>spearman</sub> = 0.6249, p = 0.025; r<sub>spearman</sub> = 0.6714, <i>p</i> = 0.015, respectively), with CD13-positive tumors showing significant radiotracer accumulation.</p> Conclusion <p>CD13 was a potential target for PSMA-negative PCa and also showed high positivity rates in PSMA-positive PCa, DAC, and IDC-P. [<sup>18</sup>F]AlF-CD13-L1 selectively accumulated in CD13-positive PCa, enabling visualization. (Trial registration: ChiCTR2300077817. Registered November 21, 2023).</p>

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CD13 as a potential theranostic target for prostate-specific membrane antigen-negative prostate cancer and first-in-human study of [18F]AlF-CD13-L1 PET/CT imaging

  • 期刊论文

  • 发表日期：

    2025年2月22日

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  • Wei Tang,
  • Ming Zhou,
  • Chenxi Lu,
  • Lin Qi,
  • Ye Zhang,
  • Yongxiang Tang,
  • Xiaomei Gao,
  • Shuo Hu,
  • Yi Cai

摘要

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 [18F]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 [18F]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 (rspearman = 0.6249, p = 0.025; rspearman = 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. [18F]AlF-CD13-L1 selectively accumulated in CD13-positive PCa, enabling visualization. (Trial registration: ChiCTR2300077817. Registered November 21, 2023).