2. Academic Validation
  3. Development and Application of Radioactive Ligands Targeting Fibroblasts with Albumin-Binding Sites

Development and Application of Radioactive Ligands Targeting Fibroblasts with Albumin-Binding Sites

  • Mol Cancer Ther. 2025 Aug 1;24(8):1186-1196. doi: 10.1158/1535-7163.MCT-24-1108.
Tongtong Wu 1 2 3,  Zhicong Yang 1 2 3,  Sufan Tang 1 2 3,  Hongmei Yuan 1 2 3,  Yang Liu 1 2 3,  Haiyang Li 1 2 3,  Nan Liu 4,  Zhanwen Huang 1 2 3 5,  Yue Chen 1 2 5,  Zhijun Zhou 1 2 3 5
Affiliations

Affiliations

  • 1 Department of Nuclear Medicine, Affiliated Hospital of Southwest Medical University, Luzhou, China.
  • 2 Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China.
  • 3 Department of Pharmaceutics, School of Pharmacy, Southwest Medical University, Luzhou, China.
  • 4 Department of Nuclear Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.
  • 5 Academician (Expert) Workstation of Sichuan Province, Luzhou, China.
PMID: 40177850 DOI: 10.1158/1535-7163.MCT-24-1108
Abstract

Fibroblast activation protein (FAP) is overexpressed on cancer-associated fibroblasts, making it an important target for Cancer diagnosis and treatment, but limited tumor retention hinders late-stage diagnosis and radionuclide therapy. In this study, three albumin-bound FAP Inhibitor (FAPI) radioligands, 68Ga/177Lu-DOTA-ALB-01, 68Ga/177Lu-DOTA-ALB-02, and 68Ga/177Lu-DOTA-ALB-03, were synthesized and evaluated for their in vitro stability, binding affinity, in vivo biodistribution, and tumor uptake using 68Ga and 177Lu labeling. All radioligands are stable in saline and plasma and exhibit high FAP-binding affinity. 177Lu-DOTA-ALB-02 has longer retention in circulation than 177Lu-FAPI-46 and Other radioligands. Continuous tumor accumulation was observed during imaging with both 177Lu-DOTA-ALB-01 and 177Lu-DOTA-ALB-02. Notably, 177Lu-DOTA-ALB-02 had a significant tumor/nontarget ratio as indicated by biodistribution data. The outstanding tumor retention properties of 177Lu-DOTA-ALB-02 have been demonstrated in small-animal single-photon emission computed tomography imaging and biodistribution studies; therefore, it is considered the albumin-binding FAPI with the most favorable pharmacokinetic and imaging properties, worthy of further clinical investigation.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-175613
    FAPI Ligand
    FAP