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Aza-BODIPY: A New Vector for Enhanced Theranostic Boron Neutron Capture Therapy Applications

Abstract : Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on the nuclear capture of slow neutrons by stable 10 B atoms followed by charged particle emission that inducing extensive damage on a very localized level (<10 µm). To be efficient, a sufficient amount of 10 B should accumulate in the tumor area while being almost cleared from the normal surroundings. A water-soluble aza-boron-dipyrromethene dyes (BODIPY) fluorophore was reported to strongly accumulate in the tumor area with high and BNCT compatible Tumor/Healthy Tissue ratios. The clinically used 10 B-BSH (sodium borocaptate) was coupled to the water-soluble aza-BODIPY platform for enhanced 10 B-BSH tumor vectorization. We demonstrated a strong uptake of the compound in tumor cells and determined its biodistribution in mice-bearing tumors. A model of chorioallantoic membrane-bearing glioblastoma xenograft was developed to evidence the BNCT potential of such compound, by subjecting it to slow neutrons. We demonstrated the tumor accumulation of the compound in real-time using optical imaging and ex vivo using elemental imaging based on laser-induced breakdown spectroscopy. The tumor growth was significantly reduced as compared to BNCT with 10 B-BSH. Altogether, the fluorescent aza-BODIPY/ 10 B-BSH compound is able to vectorize and image the 10 B-BSH in the tumor area, increasing its theranostic potential for efficient approach of BNCT.
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Submitted on : Thursday, September 17, 2020 - 9:42:56 AM
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Ghadir Kalot, Amélie Godard, Benoît Busser, Jacques Pliquett, Mans Broekgaarden, et al.. Aza-BODIPY: A New Vector for Enhanced Theranostic Boron Neutron Capture Therapy Applications. Cells, MDPI, 2020, 9 (9), pp.1953. ⟨10.3390/cells9091953⟩. ⟨inserm-02941457⟩



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