Active-Targeted ICG for Surgical Navigation and Fluorescence-Guided Laparoscopic Photothermal Ablation in Pancreatic Ductal Adenocarcinoma

  • Anal Chem. 2025 Jan 14;97(1):473-481. doi: 10.1021/acs.analchem.4c04575.
Lei Zhou  1 Manxiong Dai  1  2 Jiahao Zhou  1  2 Xingyang Zhao  3 Zixiong Liu  1 Hao Bu  1 Yang Zhou  4 Yan Liao  1 Hongwen Liu  1  5 Wei Cheng  1 Kang Chen  1
Affiliations
  • 1. Department of Hepatobiliary Surgery, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, Hunan Province China.
  • 2. Department of Biomedical Sciences, University of Macau, Macau SAR 999078, China.
  • 3. Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou 510080, China.
  • 4. Department of Hepatobiliary Surgery, The Affiliated Changsha Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan Province 410005, China.
  • 5. Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research, College of Chemistry and Chemical Engineering, Hunan Normal University, Changsha, Hunan Province 410005, 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.

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