2. Academic Validation
  3. FGF2-Based Cyclic Peptide PET Tracer for Noninvasive Detection of FGFR1 Expression in Non-Small Cell Lung Cancer

FGF2-Based Cyclic Peptide PET Tracer for Noninvasive Detection of FGFR1 Expression in Non-Small Cell Lung Cancer

  • J Med Chem. 2026 Feb 26;69(4):4755-4770. doi: 10.1021/acs.jmedchem.5c03417.
Yan Xue 1 2,  Zhihong Huang 1 2,  Xue Zhu 1 2,  Shuang Wang 1 2,  Yang Jiao 1 2,  Xun Wang 3,  Jie Tang 1 2,  Dong Xu 1 2,  Yongchang Zhang 4,  Qian Wang 5,  Chunwei Xu 6,  Jing Fang 1 2,  Ke Wang 1 2
Affiliations

Affiliations

  • 1 National Health Commission Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu 214063, China.
  • 2 Department of Radiopharmaceuticals, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
  • 3 Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, China.
  • 4 Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China.
  • 5 Department of Respiratory Medicine, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, China.
  • 6 Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China.
PMID: 41700010 DOI: 10.1021/acs.jmedchem.5c03417
Abstract

FGFR1 overexpression is strongly correlated with tumorigenesis, malignant progression, and poor clinical outcomes of nonsmall cell lung Cancer (NSCLC). The development of PET radiotracers specifically targeting FGFR1 holds significant clinical value for guiding FGFR1-targeted therapy, evaluating treatment efficacy, and monitoring drug resistance. In this study, we used computational simulation approaches to develop linear peptide RY9 along with cyclic peptides cRY9 and cRY9M, derived from FGF2, a particular ligand of FGFR1, and designed FGFR1-targeting radiotracers [68Ga]Ga-NOTA-RY9, [68Ga]Ga-NOTA-cRY9 and [68Ga]Ga-NOTA-cRY9M for detecting the FGFR1 expression. In comparison to [68Ga]Ga-NOTA-RY9 and [68Ga]Ga-NOTA-cRY9, [68Ga]Ga-NOTA-cRY9M demonstrated superior FGFR1-binding affinity, enhanced in vivo stability, and a significantly improved tumor-to-background ratio (TBR). Notably, PET imaging revealed that [68Ga]Ga-NOTA-cRY9M exhibited significant and specific tumor uptake in FGFR1-positive NSCLC cell-derived xenograft (CDX) models and patient-derived xenograft (PDX) models. These results demonstrate that the cyclic peptide-based radiotracer [68Ga]Ga-NOTA-cRY9M serves as a potential diagnostic agent for FGFR1-expressing tumors.

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