2. Academic Validation
  3. Development and bioevaluation of 18F-labeled bivalent cyclic peptides for PET imaging of αvβ6 integrin overexpression

Development and bioevaluation of 18F-labeled bivalent cyclic peptides for PET imaging of αvβ6 integrin overexpression

  • Bioorg Chem. 2025 Mar 12:159:108362. doi: 10.1016/j.bioorg.2025.108362.
Shimin Ye 1,  Dazhi Shi 1,  Xuefei Li 2,  Yali Yang 1,  Xingzhu Pan 1,  Lijuan Wang 3,  Hubing Wu 4
Affiliations

Affiliations

  • 1 GDMPA Key Laboratory for Quality Control and Evaluation of Radiopharmaceuticals, Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Road, Guangzhou, Guangdong Province 510515, China.
  • 2 Central Research Institute, United Imaging Healthcare, 2258 Chengbei Road, Shanghai 201807, China.
  • 3 GDMPA Key Laboratory for Quality Control and Evaluation of Radiopharmaceuticals, Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Road, Guangzhou, Guangdong Province 510515, China. Electronic address: wljhaiyin@163.com.
  • 4 GDMPA Key Laboratory for Quality Control and Evaluation of Radiopharmaceuticals, Department of Nuclear Medicine, Nanfang Hospital, Southern Medical University, 1838 Guangzhou North Road, Guangzhou, Guangdong Province 510515, China. Electronic address: wuhbym@163.com.
PMID: 40096805 DOI: 10.1016/j.bioorg.2025.108362
Abstract

Integrin αvβ6 has emerged as a critical target in Cancer diagnostics and therapeutics. In this study, we developed two bivalent ligands, NOTA-(SDM17)2 and NOTA-(AvB6)2, for positron emission tomography (PET) imaging of αvβ6 integrins. Surface plasmon resonance (SPR) revealed affinities for NOTA-(SDM17)2 and NOTA-(AvB6)2 with KD values of 2.15 μM and 5.21 μM, respectively. Micro-PET imaging demonstrated significantly higher uptake of [18F]AlF-NOTA-(SDM17)2 and [18F]AlF-NOTA-(AvB6)2 in H2009 tumors (αvβ6-positive) compared to MDA-MB-231 tumors (αvβ6-negative) ([18F]AlF-NOTA-(SDM17)2: 3.2 ± 0.3 vs. 0.3 ± 0.07 %ID/g; [18F]AlF-NOTA-(AvB6)2: 6.4 ± 0.5 vs. 1.0 ± 0.2 %ID/g at 60 min p.i., P < 0.05). Both bivalent tracers exhibited enhanced tumor uptake and retention relative to their monovalent counterparts ([18F]AlF-NOTA-SDM17 and [18F]AlF-NOTA-AvB6) at 60 min p.i., (P < 0.05). Notably, [18F]AlF-NOTA-(SDM17)2 demonstrated a superior tumor-to-liver ratio (13.24 vs. 5.93, P = 0.029) and longer retention, as confirmed by in vivo biodistribution studies. These findings highlight the potential of [18F]AlF-NOTA-(SDM17)2 and [18F]AlF-NOTA-(AvB6)2 as bivalent PET tracers to enhance tumor uptake and prolong retention. Among them, [18F]AlF-NOTA-(SDM17)2 shows particular promise for clinical translation due to its higher tumor-to-non-tumor ratio and prolonged retention.

Keywords

Bivalent ligand; Fluorine-18; Integrins; Positron emission tomography(PET); αvβ6 overexpression.

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