2. Academic Validation
  3. High Affinity and FAP-Targeted Radiotracers: A Potential Design Strategy to Improve the Pharmacokinetics and Tumor Uptake for FAP Inhibitors

High Affinity and FAP-Targeted Radiotracers: A Potential Design Strategy to Improve the Pharmacokinetics and Tumor Uptake for FAP Inhibitors

  • J Med Chem. 2023 Jul 13;66(13):8614-8627. doi: 10.1021/acs.jmedchem.3c00259.
Yinwen Wang 1 2 3,  Hongmei Yuan 1 2 3,  Nan Liu 4,  Sufan Tang 1 2 3,  Yue Feng 1 2 5,  Yang Liu 1 2 5,  Ping Cai 1 2 3,  Li Xia 1 2 3,  Wenlu Zheng 1 2 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, Sichuan 646000, China.
  • 2 Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan 646000, China.
  • 3 Department of Pharmaceutics, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China.
  • 4 Department of Nuclear Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan 610072, China.
  • 5 Institute of Nuclear Medicine, Southwest Medical University, Luzhou, Sichuan 646000, China.
PMID: 37390480 DOI: 10.1021/acs.jmedchem.3c00259
Abstract

Fibroblast activation protein (FAP) is overexpressed in cancer-associated fibroblasts, making it an attractive target for both imaging and therapy of malignancy. This study presents a range of novel FAP inhibitors derived from amino derivatives of UAMC1110, incorporating polyethylene glycol and bulky groups containing bifunctional DOTA chelators. The compounds labeled with gallium-68 were developed and characterized to study biodistribution properties and tumor-targeting performance in nude mice bearing U87MG tumor xenografts. Several tracers of interest were screened due to the advantages in imaging and tumor-specific uptake. Positron emission tomography scans revealed that polyethylene glycol-modified 68Ga-3-3 had a rapid penetration within the neoplastic tissue and excellent tumor-to-background contrast. In a comparative biodistribution study, naphthalene-modified 68Ga-6-3 exhibited more significant tumor uptake (∼50% ID/g, 1 h p.i.) than 68Ga-3-3 and 10-fold higher than 68Ga-FAPI-04 under the same conditions. Remarkably, 68Ga-8-1, combining the two structural design strategies, obtains superior imaging performance.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-149860
    FAP Inhibitor
    FAP