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Updated: Apr 23, 2026
![Automated Preparation of [68Ga]Ga-3BP-3940 on a Synthesis Module for PET Imaging of the Tumor Microenvironment](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F68356.jpg&w=3840&q=50)
Automated Preparation of [68Ga]Ga-3BP-3940 on a Synthesis Module for PET Imaging of the Tumor Microenvironment
Published on: April 25, 2025
Development of Lipid-Engineered PSMA-Targeted Radioligands with Quinoline Scaffold
Tao Zhang1, Zhexin He1, Yaoxuan Wang1
1State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, Fujian Engineering Research Center of Molecular Theranostic Technology, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, Fujian 361102, China.
None:
Prostate-specific membrane antigen (PSMA) is highly overexpressed in prostate cancer, making it an effective diagnostic biomarker and therapeutic target for PCa. However, many PSMA-targeted small-molecule probes suffer from suboptimal tumor uptake and retention. In this study, a series of PSMA ligands were rationally designed and synthesized using classical lipidation and fatty acid modification strategies, and subsequently labeled with 68Ga/177Lu to address these limitations. Cellular studies and molecular docking simulations confirmed their PSMA specificity and protein-binding properties. In a PC-3 PIP xenograft mouse model, nine 68Ga-labeled PSMA-targeted radioligands were evaluated using PET imaging. Among them, [68Ga]Ga-PDA2-C6 and [68Ga]Ga-PDA1-1 demonstrated remarkable tumor accumulation and retention, with improved tumor-to-nontarget (T/NT) ratios. Biodistribution studies further revealed pronounced tumor retention of [177Lu]Lu-PDA2-C6 and [177Lu]Lu-PDA1-1. Overall, this proof-of-concept study validated that conjugating PSMA ligands with tailor-made lipid chain and fatty acids can markedly enhance tumor uptake and retention while maintaining a low level of kidney retention.
