Dansylated Amino Acid–Modified Long-Acting PSMA Derivatives68Ga/177Lu-LNC1011 as Prostate Cancer Theranostics

作者：Hongzhang Yang, Jiarou Wang, Xuejun Wen, Huifeng Guo, Vivianne Jakobsson, Tianzhi Zhao, Fantian Zeng, Huaxiang Shen, Heng Zhang, Chao Li, Yatong Qin, Xinyi Li, Hehe Xiong, Zijian Zhou, Jingjing Zhang, Xiaoyuan Chen · 发表于：Journal of Nuclear Medicine · 年份：2025 · DOI：10.2967/jnumed.124.268959 · 被引用次数：5 · 研究领域：Radiopharmaceutical Chemistry and Applications、Prostate Cancer Treatment and Research、Mass Spectrometry Techniques and Applications

Prostate-specific membrane antigen (PSMA)–targeted radiopharmaceutical therapy has demonstrated promising potential for treating metastatic castration-resistant prostate cancer. Recently, albumin-binding motif-modified PSMA radioligands with prolonged blood circulation were developed to improve tumor uptake and therapeutic effectiveness, properties which, however, were associated with an increased risk of bone marrow toxicity. This study presents new PSMA-targeted radioligands incorporating dansylated amino acids as relatively weak and preferable albumin binders to achieve a fine balance between increased tumor accumulation, safety, and diagnostic efficacy, facilitating a unified approach to theranostics within a single molecular framework. Methods: Three novel PSMA ligands ([ 68 Ga]Ga-Dan-Gly-PSMA, [ 68 Ga]Ga-Dan-Nva-PSMA, and [ 68 Ga]Ga-Dan-Phe-PSMA, denoted as [ 68 Ga]Ga-LNC1011) were synthesized with dansylated amino acids and measured the albumin-binding properties with human serum albumin through ultrafiltration experiments. Binding affinity and PSMA-targeting specificity were investigated using a saturation binding assay and cell uptake in the PSMA-induced prostate cancer 3 cell line (PC3-PIP). PET imaging in PC3-PIP tumor–bearing mice was performed to evaluate the preclinical pharmacokinetics and diagnostic efficiency of 68 Ga-labeled PSMA ligands. Tumor uptake of [ 177 Lu]Lu-LNC1011 was evaluated through SPECT/CT imaging and biodistribution studies. Radiopharmaceu...