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Updated: Jun 3, 2025
Tissue-simulating Phantoms for Assessing Potential Near-infrared Fluorescence Imaging Applications in Breast Cancer Surgery
Published on: September 19, 2014
Monomeric or Homodimer Conjugates of Fibroblast Activation Protein Inhibitor and Cyanine 7 Bearing a Meso-Chloride as
Panpan Chen1, Zhipeng Lu2, Xiaowei Feng1
1Department of Radiopharmaceuticals, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.
Abstract:
Intraoperative fluorescence navigation can illuminate the tumor, directing surgeons to accurately achieve negative margins, which not only reduces recurrence but also minimizes the incidence of complications. Herein, we developed two near-infrared fluorescent probes FAPI-Cy7-Cl (Emmax = 820 nm) and (FAPI)-Cy7-Cl (Emmax = 823 nm) with prolonged tumor retention (>72 h) and high target-to-background ratios (up to 4.5) based on the conjugation of pan-cancer targeted fibroblast activation protein inhibitor (FAPI) and the "tumor-seeking" Cyanine 7 bearing a meso-chloride and a cyclohexenyl skeleton (Cy7-Cl). Specifically, FAPI-Cy7-Cl exhibited superior imaging performance in both estrogen receptor α positive breast cancer (MCF-7) and triple-negative breast cancer (TNBC) (MDA-MB-231) subtypes in mouse models. Notably, in the MDA-MB-231 tumor-bearing model, the tumor-to-liver ratio (T/L) of FAPI-Cy7-Cl increased rapidly after 2 h postinjection, reaching nearly 4.5 at 48 h, making it an optimal imaging probe for guiding TNBC surgery resection.
Insights
New near-infrared fluorescent probes, FAPI-Cy7-Cl and (FAPI)-Cy7-Cl, enhance tumor visualization during surgery. These probes improve negative margin achievement and reduce complications in breast cancer models.
Area of Science:
- Oncology
- Medical Imaging
- Organic Chemistry
Background:
- Intraoperative fluorescence navigation aids surgeons in achieving negative margins, reducing tumor recurrence and complications.
- Fibroblast Activation Protein Inhibitor (FAPI) is a pan-cancer target, and Cyanine 7 (Cy7) is a near-infrared fluorophore.
- Developing targeted fluorescent probes is crucial for precise surgical guidance.
Purpose of the Study:
- To develop novel near-infrared fluorescent probes for enhanced intraoperative tumor imaging.
- To evaluate the tumor retention and target-to-background ratios of the developed probes.
- To assess the imaging performance of the probes in different breast cancer subtypes.
Main Methods:
- Conjugation of pan-cancer targeted FAPI with a modified Cy7 fluorophore (Cy7-Cl) to create FAPI-Cy7-Cl and (FAPI)-Cy7-Cl probes.
- Characterization of probe properties, including emission maxima, tumor retention, and target-to-background ratios.
- In vivo imaging studies using estrogen receptor α positive (MCF-7) and triple-negative breast cancer (TNBC) (MDA-MB-231) mouse models.
Main Results:
- Two probes, FAPI-Cy7-Cl (Emmax = 820 nm) and (FAPI)-Cy7-Cl (Emmax = 823 nm), were successfully synthesized.
- Both probes demonstrated prolonged tumor retention (>72 h) and high target-to-background ratios (up to 4.5).
- FAPI-Cy7-Cl showed superior performance in both MCF-7 and MDA-MB-231 models, with a notable tumor-to-liver ratio of nearly 4.5 at 48 h in the TNBC model.
Conclusions:
- FAPI-Cy7-Cl and (FAPI)-Cy7-Cl are effective near-infrared fluorescent probes for intraoperative tumor visualization.
- FAPI-Cy7-Cl is particularly promising for guiding triple-negative breast cancer surgery due to its high tumor-to-liver ratio and rapid uptake.
- These probes have the potential to improve surgical outcomes by enabling more accurate tumor resection.
