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 10B atoms followed by charged particle emission that inducing extensive damage on a very localized level (<10 μm). To be efficient, a sufficient amount of 10B 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 10B-BSH (sodium borocaptate) was coupled to the water-soluble aza-BODIPY platform for enhanced 10B-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 10B-BSH. Altogether, the fluorescent aza-BODIPY/10B-BSH compound is able to vectorize and image the 10B-BSH in the tumor area, increasing its theranostic potential for efficient approach of BNCT.

Theranostics in Boron Neutron Capture Therapy

“…In preclinical stages, aza-BODIPY derivatives were investigated to enhance the vectorization of BSH in tumors. While currently visualized with optical imaging in the SWIR region, the aza-BODIPY derivatives may also be modified to add a small chelate such as DOTA moiety that could be used for nuclear imaging [ 62 ].…”

“…Ex-vivo, the quantification and the distribution of boron in tissues are also possible using elemental imaging. Such modalities might give some additional and valuable information at the cell and the tissue scales, using secondary ion mass spectrometry (SIMS) [ 63 ], laser secondary neutral mass spectrometry (laser-SNMS) [ 64 , 65 ], or laser-induced breakdown spectroscopy (LIBS) [ 62 ]. LIBS is an all-optical technique working at room temperature and atmosphere, allowing the reconstruction of elemental imaging from the mapping of a sample.…”

FLUOROFÓROS Aza-BODIPY: ESTRATÉGIAS DE SÍNTESE E APLICAÇÕES

“…Estas são as três principais e mais abrangentes rotas sintéticas de aza-BODIPY's; nos núcleos já sintetizados, várias modificações estruturais podem ser realizadas à fim de modular as características e propriedades desejáveis nos compostos-alvo 18 . Dentre estas características as mais realizadas são modificações para melhorar características fotofísicas 16,19,20 e aumentar hidrofilicidade/biocompatibilidade [21][22][23][24] .…”

Methodology for the Implementation of Internal Standard to Laser-Induced Breakdown Spectroscopy Analysis of Soft Tissues

“…This was demonstrated by using gadolinium based nanoparticles [ 36 ] and zwitterionic gold nanoclusters in glioblastoma mouse models [ 37 ]. The homogeneity of boron distribution within tumors was assessed by LIBS and further studied by fluorescence imaging [ 38 ]. The retention of both La and Ce in various organs of long-term glioblastoma survivors was observed on cryosections with 25 µm resolution [ 39 ].…”