Related Experiment Video
Updated: May 16, 2026
Development of a 68Gallium-Labeled D-Peptide PET Tracer for Imaging Programmed Death-Ligand 1 Expression
Published on: February 3, 2023
Chemically Evolved Integrin α5β1-Targeted Peptide PET Tracers for Orthotopic Pancreatic Ductal Adenocarcinoma
Xin Gao1,2, Linger Li1,2, Siqi Zhang1,2
1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) remains a lethal malignancy characterized by a dense desmoplastic microenvironment. Integrin α5β1 mediates tumor-stroma interactions via fibronectin binding and is markedly upregulated in PDAC, making it an attractive drug target; however, α5β1-targeted radiotracers for PDAC imaging remain scarce. Here, we developed α5β1-targeted peptide radiotracers to evaluate their preclinical potential for PET/CT imaging of PDAC. Using the fibronectin-derived peptide AV3 (RYYRITY) as a scaffold, we performed stepwise chemical evolution through alanine scanning and noncanonical amino acid engineering, leading to a focused library of 15 structurally evolved AV3 analogues radiolabeled with gallium-68. The radiotracers were systematically evaluated by in vitro assays, microPET/CT imaging, and ex vivo biodistribution. Among them, [68Ga]Ga-HKA-008 exhibited enhanced stability, increased tumor uptake, and improved retention compared with [68Ga]Ga-DOTA-AV3. Notably, [68Ga]Ga-HKA-008 demonstrated notable uptake in orthotopic pancreatic tumors in vivo, suggesting the feasibility of α5β1-targeted radiotracers for PDAC imaging.
