Active-Targeted ICG for Surgical Navigation and Fluorescence-Guided Laparoscopic Photothermal Ablation in Pancreatic
Lei Zhou1, Manxiong Dai1,2, Jiahao Zhou1,2
1Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, Hunan Province China.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy, but there is limited improvement in its treatment. Near-infrared fluorescence (NIRF) imaging could potentially address the clinical challenges of PDAC. Indocyanine green (ICG) has been widely used in clinical practice; however, its short half-life and lack of active targeting greatly limit its application in pancreatic surgery. In this study, the active targeting peptide KTLLPTP (which actively recognizes PDAC cell surface overexpression Plectin-1) was modified to the ICG to create the novel contrast agent ICG-PTP, which actively targets PDAC cells. It was successfully applied to the NIRF imaging of the PDAC orthotopic mice model, achieving an improved tumor signal background ratio (T/N ratio) of 4.28, compared to 2.34 in the free ICG group. Next, Fluorescence-guided excision of subcutaneous/orthotopic PDAC using ICG-PTP was performed, accurately identifying the tumor margin and significantly facilitating resection efficiency. Finally, PDAC metastases were identified, and interventional photothermal ablation (iPTA) was performed under fluorescence laparoscope guidance. ICG-PTP exhibits good biosafety and clinical transitional potential. Thus, they can provide surgeons with efficient real-time tumor information and offer new treatment strategies for metastases. Accordingly, modification of probes for clinical use and adaptation studies of current equipment are the current focus.
Insights
A novel near-infrared fluorescence (NIRF) imaging agent, ICG-PTP, actively targets pancreatic ductal adenocarcinoma (PDAC). This agent improves tumor visualization and facilitates surgical resection and metastasis treatment, showing clinical potential.
Area of Science:
- Oncology
- Medical Imaging
- Biotechnology
Background:
- Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with limited treatment options.
- Near-infrared fluorescence (NIRF) imaging offers potential for improved PDAC diagnosis and treatment.
- Current agents like Indocyanine green (ICG) have limitations such as short half-life and lack of active targeting.
Purpose of the Study:
- To develop and evaluate a novel actively targeted NIRF contrast agent for PDAC.
- To assess the efficacy of ICG-PTP in enhancing tumor visualization and guiding surgical resection.
- To explore the potential of ICG-PTP in identifying metastases and guiding interventional photothermal ablation (iPTA).
Main Methods:
- Modification of ICG with an active targeting peptide (KTLLPTP) recognizing Plectin-1 to create ICG-PTP.
- Application of ICG-PTP in a PDAC orthotopic mice model for NIRF imaging.
- Evaluation of fluorescence-guided excision and interventional photothermal ablation (iPTA) under fluorescence laparoscope guidance.
Main Results:
- ICG-PTP achieved a significantly higher tumor-to-background ratio (T/N ratio) of 4.28 compared to free ICG (2.34).
- Fluorescence-guided surgery using ICG-PTP accurately identified tumor margins and improved resection efficiency.
- PDAC metastases were successfully identified, enabling targeted interventional photothermal ablation.
Conclusions:
- ICG-PTP is a novel, actively targeted NIRF contrast agent with good biosafety and potential for clinical translation in PDAC.
- This agent can provide real-time tumor information to surgeons, enhancing surgical precision.
- ICG-PTP offers new therapeutic strategies for PDAC, particularly for managing metastases.
