Rational Design and Synthesis of Peptide-Based Probes for Fibroblast Activation Protein-Targeted Magnetic Resonance and NIR-I/II Fluorescence Imaging of Cancer-Associated Fibroblasts
- Xiaoyu Wang 1, Rongfeng Zou 2, Ningxin Yang 1, Weixi Huang 1, Chunting Wang 1, Yuelin Huang 1, Yanhong Chen 1, Dengbin Wang 1,3, Gang Ren 1, Defan Yao 1
- Xiaoyu Wang 1, Rongfeng Zou 2, Ningxin Yang 1
- 1Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
- 2Department of Physics and Astronomy, Uppsala University, Box 516, Uppsala SE-75120, Sweden.
- 3College of Health Science and Technology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
- 0Department of Radiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
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View abstract on PubMed
Summary
This summary is machine-generated.Novel dual-modality imaging probes targeting cancer-associated fibroblasts (CAFs) were developed. These probes enhance visualization of CAFs in gastric cancer, improving diagnostic capabilities.
Area Of Science
- Biomedical Imaging
- Molecular Imaging
- Cancer Diagnostics
Background
- Cancer-associated fibroblasts (CAFs) expressing fibroblast activation protein (FAP) drive tumor progression and therapy resistance.
- FAP-targeted molecular imaging is crucial for visualizing and quantifying CAFs in tumors.
Purpose Of The Study
- To design and synthesize novel dual-modality probes for FAP-targeted imaging in gastric cancer.
- To evaluate the efficacy of these probes for visualizing CAFs in vivo.
Main Methods
- Rational design and synthesis of two FAP-targeted probes (FAPtp1<sup>Mn-ICG</sup> and FAPtp2<sup>Mn-ICG</sup>) using FAP-targeted peptides, Mn-NOTA, and indocyanine green (ICG).
- Integration of magnetic resonance (MR) and near-infrared fluorescence (NIRF) imaging modalities.
- In vitro specificity and biosafety assays, followed by in vivo imaging in tumor-bearing mice.
Main Results
- Successful synthesis of FAPtp1<sup>Mn-ICG</sup> and FAPtp2<sup>Mn-ICG</sup>, with FAPtp2<sup>Mn-ICG</sup> showing improved NIRF imaging efficiency due to a polyethylene glycol linker mitigating aggregation-caused quenching (ACQ).
- Both probes demonstrated high FAP-targeted specificity and biosafety in vitro.
- In vivo imaging successfully visualized subcutaneous tumors and peritoneal metastases in mice.
Conclusions
- Developed novel FAP-targeted dual-modality probes for enhanced CAF evaluation in gastric cancer.
- The polyethylene glycol linker strategy effectively improved probe performance.
- These probes offer a promising platform for advancing peptide-based molecular imaging in cancer diagnostics.
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