359P - CD13 as a potential membrane marker in PSMA-negative prostate cancer and first-in-human study of [18F]AlF-CD13-L1 PET/CT imaging

Background

PSMA PET/CT shows high accuracy in diagnosing PCa. However, approximately 10-15% of PCa are PSMA-negative. In this study, we revealed CD13 as a potential biomarker for PSMA-negative PCa. Notably, CD13 also exhibited high positivity in PSMA-positive PCa, DAC, and IDC-P. A first-in-human study was conducted to explore the feasibility of employing the CD13-targeting probe [¹⁸F] AlF-CD13-L1 for diagnosing PCa. The potential of [¹⁷⁷Lu] Lu-CD13-L1 for PCa treatment was investigated in animals.

Methods

Quantitative protein analysis was conducted on eight PSMA-negative PCa. CD13 expression was validated in an expanded cohort. Cellular uptake assays were conducted in PC-3 and RWPE-1. Small-animal PET imaging was performed in PC-3 xenograft mice. Imaging potential of [¹⁸F] AlF-CD13-L1 was assessed in sixteen volunteers. [¹⁷⁷Lu] Lu-CD13-L1 was synthesized and evaluated for therapeutic efficacy in animals.

Results

Quantitative protein analysis revealed CD13 as the most significantly upregulated membrane protein in PSMA-negative PCa. Expanded validation results indicated even disregarding PSMA expression status, CD13 was markedly overexpressed in PCa. CD13 positivity rates were 92.9%, 82.7%, 91.7%, and 70% in PSMA-negative PCa, PSMA-positive PCa, DAC, and IDC-P, respectively. PC-3 exhibited significantly higher uptake of [¹⁸F] AlF-CD13-L1 than RWPE-1. [¹⁸F] AlF-CD13-L1 allowed PC-3 tumor visualization, with tumor uptake value and tumor-to-muscle ratio of 1.6 %ID/g and 15, respectively. In PCa patients, the median SUVmax of tumors and tumor-to-muscle ratio were 4.4 and 5.3, respectively. Tumor [¹⁸F] AlF-CD13-L1 uptake positively correlated with CD13 expression, with CD13-positive tumors showing significant radiotracer accumulation. [¹⁷⁷Lu] Lu-CD13-L1 effectively inhibited PC-3 tumor growth, extending median mouse survival from 33 to 69 days.

Conclusions

CD13 was a potential biomarker for PSMA-negative PCa and showed high positivity rates in PSMA-positive PCa, DAC, and IDC-P. [¹⁸F] AlF-CD13-L1 selectively accumulated in CD13-positive PCa, enabling visualization. [¹⁷⁷Lu] Lu-CD13-L1 targeted and eliminated CD13-positive tumor cells, extending xenograft mouse survival.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

This research was supported by the Outstanding Youth Fund Project of Hunan Province (2024JJ2090, 2024JJ2094), the Clinical Research Foundation of the National Clinical Research Center for Geriatric Diseases (XIANGYA) (2023LNJJ13, 2023LNJJ16, 2020LNJJ01), the National Natural Science Foundation of China (82272907, 81974397, 81572524, 91859207, 81771873, 82272045, 82273121, 91859207, 81801740), Key Research and Development Program of Hunan Province (2023SK2017), Key Program of Ministry of Industry and Information Technology of China (CEIEC-2022-ZM02-0219), Science and Technology Innovation Program of Hunan Province (2021RC4056), the National Key Research and Development Plan (2017YFC0908004), the Clinical Big Data System Construction Project Fund of Xiangya Hospital (No. 33020125030), the Xiangya Famous Doctor Fund of Central South University (33020123007), the Fundamental Research Funds for the Central Universities of Central South University (1053320220574), China Postdoctoral Science Foundation (2022M23561).

Disclosure

All authors have declared no conflicts of interest.