Progress in Integrin Targeted Radionuclide Therapy
10.11714/jsysu.med.YX20260102
- VernacularTitle:整合素靶向放射性核素治疗进展
- Author:
Yonghao LI
1
;
Jiangyan LIU
1
Author Information
1. Department of Nuclear Medicine， Lanzhou University Second Hospital， Lanzhou 730030， China
- Publication Type:Review
- Keywords:
integrin αvβ3;
radionuclide therapy;
dual-targeting strategy;
α radionuclides;
cancer theranostics
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2026;47(5):799-808
- CountryChina
- Language:Chinese
-
Abstract:
Integrin αvβ3 is an important target for tumor imaging and therapy. It is highly expressed on tumor neovascular endothelial cells and various malignant tumor cells， while being nearly absent in normal tissues and quiescent endothelial cells. Positron emission tomography （PET） based on Arg-Gly-Asp （RGD） peptides has been widely applied， yet single-target strategies are limited by tumor heterogeneity. β- radionuclide-labeled RGD peptides exhibit problems of insufficient tumor uptake and renal accumulation. This review summarizes the preclinical progress in two frontier directions. Dual-targeting strategies combine integrin αvβ3 with prostate-specific membrane antigen （PSMA） or fibroblast activation protein （FAP） to construct heterodimeric probes. Preclinical and clinical studies have demonstrated that dual-targeting probes achieve significantly superior tumor uptake， target-to-background ratios， and lesion detection rates compared to single-target controls， effectively overcoming tumor heterogeneity and improving tumor uptake and detection rate. α radionuclides， by leveraging high linear energy transfer and short tissue range， demonstrate superior antitumor efficacy over β-radionuclides. In terms of clinical translation， the albumin-binding RGD dimer labeled with lutetium-177 （¹⁷⁷Lu-AB-3PRGD₂） has completed a first-in-human study， preliminarily validating the clinical feasibility of integrin-targeted radionuclide therapy， albeit with limited antitumor activity. Future directions include molecular imaging-based patient selection， optimization of dual-targeting molecular structures， and development of α radionuclide formulations.
