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Aminopeptidase N Activatable Fluorescent Probe for Tracking Metastatic Cancer and Image-Guided Surgery via in Situ
Haidong Li1,2, Qichao Yao1, Wen Sun1,3
1State Key Laboratory of Fine Chemicals, Dalian University of Technology, 2 Linggong Road, Hi-Tech Zone, Dalian 116024, P. R. China.
Abstract:
The recurrence of malignant tumors is mostly caused by incompleted surgical resection. Especially, it is difficult for surgeons to detect and accurately remove metastatic tumors by predominantly using visual examination and palpation owing to the lack of effective means to specifically distinguish the boundary range between normal and tumor tissues. Thus, the development of activated fluorescent probe with superior tumor-to-normal (T/N) tissue ratios is particularly urgent in clinics. In view of CD13/aminopeptidase N (APN) regarded as a cancer-specific biomarker, mediating with progression, invasion, and migration of malignant tumor, herein, we reported an APN-responsive fluorescent probe YH-APN and demonstrated its application to distinguish cancer cells. Through in situ spraying manner, fluorescent superior tumor-to-normal (T/N) tissue ratios (subcutaneous transplantation tumor, 13.86; hepatic metastasis, 4.42 and 6.25; splenic metastasis, 4.99) were achieved. More importantly, we have demonstrated the ability to image metastasis tumor tissue less than 1 mm in diameter, highlighting the potential for this probe to be used as a tool in surgical resection. This research may spur the use of enzyme-activatable fluorescent probes for the progress of tumor diagnosis and image-guided surgery (IGS).
Insights
A new fluorescent probe, YH-APN, effectively distinguishes cancerous tissue from normal tissue by responding to CD13/aminopeptidase N (APN). This probe aids in detecting small metastatic tumors, improving surgical resection and image-guided surgery (IGS).
Area of Science:
- Biomedical Engineering
- Oncology
- Medical Imaging
Background:
- Incomplete surgical resection is a primary cause of malignant tumor recurrence.
- Current methods like visual examination and palpation lack specificity in distinguishing tumor boundaries from normal tissue.
- CD13/aminopeptidase N (APN) is a cancer-specific biomarker associated with tumor progression and metastasis.
Purpose of the Study:
- To develop an activated fluorescent probe responsive to APN for improved tumor detection.
- To evaluate the probe's efficacy in achieving high tumor-to-normal (T/N) tissue ratios.
- To demonstrate the probe's potential in image-guided surgery (IGS).
Main Methods:
- An APN-responsive fluorescent probe, YH-APN, was synthesized and characterized.
- The probe was applied via an in situ spraying method.
- Tumor-to-normal (T/N) tissue ratios were quantified in subcutaneous tumors and metastatic models (hepatic and splenic).
Main Results:
- The YH-APN probe achieved superior T/N ratios in various tumor models (e.g., 13.86 for subcutaneous tumors, 4.99 for splenic metastasis).
- The probe successfully imaged metastatic tumor tissues as small as 1 mm in diameter.
- Demonstrated high specificity and sensitivity in distinguishing tumor margins.
Conclusions:
- The APN-responsive fluorescent probe YH-APN shows significant potential for accurate tumor margin delineation.
- This probe can enhance the detection of small metastatic lesions, crucial for complete surgical resection.
- Enzyme-activatable fluorescent probes represent a promising advancement for tumor diagnosis and image-guided surgery.
