From tumor imaging probes to boron neutron capture therapy: a strategy for designing targeted boron carriers for pancreatic Cancer.

Pancreatic cancer is characterized by late detection, early metastatic dissemination, therapy resistance, and a dense desmoplastic stroma that restricts drug access. Surgical resection with adjuvant chemotherapy confers only modest short-term benefit, but systemic toxicity, acquired chemoresistance, and postoperative relapse constrain long-term survival. Boron neutron capture therapy (BNCT) is a binary radiotherapy in which thermal neutron capture by 10B triggers the 10B(n, α)7Li reaction, releasing high-linear-energy-transfer alpha particles and lithium-7 nuclei. Their 5-9 μm range confines cytotoxicity to individual cells - an advantage over conventional radiation. However, the clinical boron agents BPA (4‑boronophenylalanine) and BSH (sodium borocaptate) lack selectivity for abdominal tumors and show poor tumor retention. Peptides and small-molecule tumor probes present an alternative delivery strategy for 10B. Relative to monoclonal antibodies, they are smaller, less immunogenic, easier to synthesize, and penetrate tissue more effectively - properties that enable selective tumor delivery when conjugated with 10B. Nonetheless, research on such probes as boron carriers has remained relatively limited. This review summarizes recent advances and ongoing challenges in BNCT for pancreatic cancer, focusing on peptide-based and small-molecule tumor probes with high tumor-to-normal tissue (T/N) ratios. It explores their design and application as novel boron carriers to address the targeting limitations of current agents and offers a perspective on advancing the clinical translation of precision BNCT for this disease.