Enhanced radiotheranostic targeting of integrin α5β1 with PEGylation-enabled peptide multidisplay platform (PEGibody): A strategy for prolonged tumor retention with fast blood clearance

• DOI: 10.1016/j.apsb.2024.07.006
• Publication Date: 2024-07-06T16:45:05Z
• Authors: Siqi Zhang; Xiaohui Ma; Jiang Wu; Jieting Shen; Yuntao Shi; Xingkai Wang; Lin Xie; Xiaona Sun; Yuxuan Wu; Hao Tian; Xin Gao; Xueyao Chen; Hongyi Huang; Lu Chen; Xuekai Song; Qichen Hu; Hailong Zhang; Feng Wang; Zhao-Hui Jin; Ming-Rong Zhang; Rui Wang; Kuan Hu
• Keywords: PEGylation; Biodistribution

Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target demonstrate inadequate in vivo performance owing to limited retention. The use of PEGylation enhance the retention by prolonging blood circulation time poses a risk increased toxicity. Therefore, strategy boosts while minimizing is urgently needed. Here, we developed PEGylation-enabled peptide multidisplay platform (PEGibody) PR_b, an peptide. PEGibody generation involved self-assembly. [64Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 200 nm diameter. Compared with non-PEGylated radioligands, demonstrated enhanced due binding affinity stability. Importantly, biodistribution analysis confirmed rapid clearance bloodstream. Administration single dose [177Lu]QM-2303 led robust antitumor efficacy. Furthermore, [64Cu]/[177Lu]QM-2303 exhibited low hematological organ toxicity both healthy tumor-bearing mice. this study presents PEGibody-based radiotheranostic approach enhances provides long-lasting effects without lifetime. radiopharmaceutical shows great potential positron emission tomography imaging-guided targeted radionuclide therapy α5β1-overexpressing tumors.