Gadolinium-functionalized fluorescent probes capable of specific enrichment in the glioblastoma, a novel method for surgery and in NCT hadrotherapy = Sonde fluorescenti funzionalizzate con gadolinio in grado di arricchirsi in modo specifico nel glioblastoma, un metodo innovativo per la chirurgia e nella adroterapia NCT

Precision medicine, advanced imaging, radiotherapy and particle therapy are becoming interconnected in modern oncology, enabling highly accurate and personalised cancer treatments. In this context, we focused on ALDH1A3, an enzyme that is overexpressed in various cancers, particularly in glioblastoma multiforme and malignant pleural mesothelioma, two rare cancers with very limited treatment options. This project has originated from a patented ALDH1A3 selective fluorescent probe (PCT/ IB2022/053216), capable of selectively illuminating tumour cells compared to healthy tissue and showing high potential to improve surgical guidance in glioblastoma. Based on this molecular scaffold, a new generation of ALDH1A-targeted therapeutic and diagnostic agents is being developed. Firstly, a new class of ALDH1A3 inhibitors is being expanded through structural optimisation. In parallel, the same scaffold is being investigated as a functionalised probe for the controlled release of gadolinium in MRI and GdNCT applications. Furthermore, the scaffold is being adapted for boron release in BNCT to generate boron-based agents. Despite significant progress, neutron capture therapies continue to face major challenges in achieving the selective release of boron and gadolinium in cancers. This work aims to address these limitations by developing a novel gadolinium-based boron-releasing scaffold that opens new doors for the application of NCT.