Acyl-CoA synthetase long-chain family member 4 (ACSL4)-targeting fluorescent probes for precision intraoperative visualization of hepatocellular carcinoma
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View abstract on PubMed
Summary
This summary is machine-generated.A new fluorescent probe targeting ACSL4 shows promise for real-time intraoperative imaging of hepatocellular carcinoma (HCC). This innovative tool enhances tumor visualization with high specificity and safety, aiding surgical precision.
Area Of Science
- Molecular Imaging
- Oncology
- Biotechnology
Background
- Hepatocellular carcinoma (HCC) diagnosis and surgical resection require improved visualization techniques.
- ACSL4 (Acyl-CoA Synthetase Long Chain Family Member 4) is identified as a potential target for HCC visualization.
- Development of targeted fluorescent probes is crucial for enhancing intraoperative imaging.
Purpose Of The Study
- To develop and validate a novel fluorescent probe targeting ACSL4 for improved intraoperative visualization of HCC.
- To assess the probe's binding affinity, specificity, biosafety, and clinical applicability in HCC.
- To evaluate the probe's potential in real-time surgical guidance for HCC.
Main Methods
- Bioinformatic analysis of transcriptomic data (TCGA, ICGC, CPTAC, GSE25097) to identify ACSL4 as a target.
- Phage display screening to identify an ACSL4-specific binding peptide (ABP).
- Conjugation of ABP with IRDye 800CW to create the fluorescent probe (ABP-IRDye 800CW); assessment of binding, specificity, and biosafety via SPR, fluorescence imaging, immunoprecipitation, histology, and blood biochemistry.
Main Results
- The ABP demonstrated moderate binding affinity to ACSL4 (Kd = 3.767 μM).
- The ABP-IRDye 800CW probe selectively targeted HCC cells with high ACSL4 expression, showing a tumor-to-background ratio (TBR) of 4.58 in PDX models.
- Histological and biochemical analyses confirmed the probe's biosafety, with no significant toxicity or impact on liver/kidney function.
Conclusions
- The novel ACSL4-targeted fluorescent probe (ABP-IRDye 800CW) is a safe and effective tool for intraoperative HCC visualization.
- The probe's high specificity and ability to correlate with ACSL4 expression levels support its potential clinical utility.
- This probe offers a promising advancement for real-time surgical guidance in HCC treatment.
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