A Comparative Study of ¹⁵⁷ Gd and ¹⁰ B Effect in a Carborane-Based Theranostic Agent for Membrane-Targeted Carbonic Anhydrase IX Inhibition and MRI-Guided Neutron Capture Therapy in Mesothelioma Treatment

High Resolution Image Download MS PowerPoint Slide This study investigates combined gadolinium and boron neutron capture therapy (GdBNCT) with carbonic anhydrase IX (CA IX) inhibition for mesothelioma treatment using a multifunctional platform (Gd-B-CA-SF). This platform incorporates a carborane cage for BNCT, a Gd complex for GdNCT/MRI, and a sulfamido group for CA IX inhibition. In vitro studies confirmed CA IX inhibition and selective binding of the compound to AB22 mesothelioma cells, with a 10-fold higher boron uptake compared to that in healthy Met-5a mesothelium. The combination of B and Gd in one molecule allows the exploration of potential additional effects coming from the nuclides 10 B and 157 Gd. Irradiation of AB22 cells showed complete tumor regrowth inhibition after treatment with 157 Gd- 10 B-CA-SF, an effect strictly related to the presence of 157 Gd and its localization on the cytosolic membrane. In vivo MRI studies confirmed higher accumulation of Gd-B-CA-SF in AB22 tumors in mice, demonstrating effective targeting. In vivo NCT experiments showed reduced tumor growth in 157 Gd- 10 B-CA-SF treated mice, confirming the effectiveness of both 157 Gd and 10 B, even at relatively low concentrations. These results demonstrate the translational potential of Gd-B-CA-SF as a theranostic agent for an innovative approach to cancer treatment.