Enhanced radiotheranostic targeting of integrin α5β1 with PEGylation-enabled peptide multidisplay platform (PEGibody): A strategy for prolonged tumor retention with fast blood clearance.
10.1016/j.apsb.2024.07.006
- Author:
Siqi ZHANG
1
;
Xiaohui MA
2
;
Jiang WU
3
;
Jieting SHEN
1
;
Yuntao SHI
1
;
Xingkai WANG
1
;
Lin XIE
4
;
Xiaona SUN
1
;
Yuxuan WU
1
;
Hao TIAN
1
;
Xin GAO
1
;
Xueyao CHEN
1
;
Hongyi HUANG
1
;
Lu CHEN
1
;
Xuekai SONG
1
;
Qichen HU
1
;
Hailong ZHANG
5
;
Feng WANG
3
;
Zhao-Hui JIN
6
;
Ming-Rong ZHANG
4
;
Rui WANG
1
;
Kuan HU
1
Author Information
1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
2. Department of Vascular and Endovascular Surgery, the First Medical Center of Chinese PLA General Hospital, Beijing 100853, China.
3. Department of Nuclear Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing 211166, China.
4. Department of Advanced Nuclear Medicine Sciences, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology (QST), Chiba 263-8555, Japan.
5. Key Laboratory of Preclinical Study for New Drugs of Gansu Province, School of Basic Medical Sciences & Research Unit of Peptide Science, Chinese Academy of Medical Sciences, Lanzhou University, Lanzhou 730000, China.
6. Department of Molecular Imaging and Theranostics, Institute for Quantum Medical Science, National Institutes for Quantum Science and Technology (QST), Chiba 263-8555, Japan.
- Publication Type:Journal Article
- Keywords:
Integrin α5β1;
Multidisplay;
PEGibody;
PEGylation;
PET imaging;
Peptide;
Targeted radionuclide therapy;
Tumor
- From:
Acta Pharmaceutica Sinica B
2025;15(2):692-706
- CountryChina
- Language:English
-
Abstract:
Peptide-based radiopharmaceuticals targeting integrin α5β1 show promise for precise tumor diagnosis and treatment. However, current peptide-based radioligands that target α5β1 demonstrate inadequate in vivo performance owing to limited tumor retention. The use of PEGylation to enhance the tumor retention of radiopharmaceuticals by prolonging blood circulation time poses a risk of increased blood toxicity. Therefore, a PEGylation strategy that boosts tumor retention while minimizing blood circulation time is urgently needed. Here, we developed a PEGylation-enabled peptide multidisplay platform (PEGibody) for PR_b, an α5β1 targeting peptide. PEGibody generation involved PEGylation and self-assembly. [64Cu]QM-2303 PEGibodies displayed spherical nanoparticles ranging from 100 to 200 nm in diameter. Compared with non-PEGylated radioligands, [64Cu]QM-2303 demonstrated enhanced tumor retention time due to increased binding affinity and stability. Importantly, the biodistribution analysis confirmed rapid clearance of [64Cu]QM-2303 from the bloodstream. Administration of a single dose of [177Lu]QM-2303 led to robust antitumor efficacy. Furthermore, [64Cu]/[177Lu]QM-2303 exhibited low hematological and organ toxicity in both healthy and tumor-bearing mice. Therefore, this study presents a PEGibody-based radiotheranostic approach that enhances tumor retention time and provides long-lasting antitumor effects without prolonging blood circulation lifetime. The PEGibody-based radiopharmaceutical [64Cu]/[177Lu]QM-2303 shows great potential for positron emission tomography imaging-guided targeted radionuclide therapy for α5β1-overexpressing tumors.
