Active-Targeted\nICG for Surgical Navigation and Fluorescence-Guided\nLaparoscopic Photothermal Ablation in Pancreatic Ductal Adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive\nmalignancy,\nbut there is limited improvement in its treatment. Near-infrared fluorescence\n(NIRF) imaging could potentially address the clinical challenges of\nPDAC. Indocyanine green (ICG) has been widely used in clinical practice;\nhowever, its short half-life and lack of active targeting greatly\nlimit its application in pancreatic surgery. In this study, the active\ntargeting peptide KTLLPTP (which actively recognizes PDAC cell surface\noverexpression Plectin-1) was modified to the ICG to create the novel\ncontrast agent ICG-PTP, which actively targets PDAC cells. It was\nsuccessfully applied to the NIRF imaging of the PDAC orthotopic mice\nmodel, achieving an improved tumor signal background ratio (T/N ratio)\nof 4.28, compared to 2.34 in the free ICG group. Next, Fluorescence-guided\nexcision of subcutaneous/orthotopic PDAC using ICG-PTP was performed,\naccurately identifying the tumor margin and significantly facilitating\nresection efficiency. Finally, PDAC metastases were identified, and\ninterventional photothermal ablation (iPTA) was performed under fluorescence\nlaparoscope guidance. ICG-PTP exhibits good biosafety and clinical\ntransitional potential. Thus, they can provide surgeons with efficient\nreal-time tumor information and offer new treatment strategies for\nmetastases. Accordingly, modification of probes for clinical use and\nadaptation studies of current equipment are the current focus.