Synthesis of Gd-DOTA-BMTP and its application in gadolinium neutron capture therapy for osteosarcoma.

Osteosarcoma (OS) represents one of the most prevalent primary malignant bone tumors affecting children and adolescents. Despite the establishment of standard treatment protocols (surgery and chemotherapy) in the 1980s, patient survival rates remain suboptimal. This underscores the critical need for the development and investigation of novel therapeutic technologies. Neutron capture therapy (NCT), an emerging precision therapeutic modality, selectively targets and eradicates tumor cells while minimizing damage to surrounding healthy tissues. In this study, we developed a novel agent, Gd-DOTA-BMTP, by attaching the cyclic nonapeptide c(CGRRAGGSC) to DOTA, followed by chelation of gadolinium (Gd) to the DOTA-BMTP. This peptide can specifically targeting osteosarcoma and binding to IL-11Rα, a cell surface receptor. Gd-DOTA-BMTP demonstrated excellent targeting specificity and a favorable biosafety profile. Furthermore, rigorous in vitro and in vivo evaluations confirmed the efficacy of Gd-DOTA-BMTP in suppressing osteosarcoma, specifically by enhancing radiosensitivity to neutron irradiation. Collectively, these findings suggest that Gd-DOTA-BMTP holds potential as a candidate for Gadolinium Neutron Capture Therapy (Gd-NCT) of osteosarcoma.