Organotrifluoroborate Sugar Conjugates for a Guided Boron Neutron Capture Therapy: From Synthesis to Positron Emission Tomography

Abstract

Sugars are a versatile tool for targeting malignant cells and have been extensively used for drug delivery and imaging techniques. Their prototype, fluorodeoxyglucose ([18F]­FDG), is currently used for positron emission tomography. Boron neutron capture therapy (BNCT) is a cancer treatment that relies on irradiation with thermal neutrons of cancer cells previously loaded with [10B]-containing compounds. The recent introduction of accelerators as a neutron source for clinical use prompts the planning of delivery compounds enriched with boron able to be traced in real time. This work describes the first synthesis of a new class of sugar derivatives conjugated to a trifluoroborate moiety as potential theranostic agents. Stability and cytotoxicity studies are reported for all compounds, together with [18F] radiolabeling optimization and in vivo preliminary positron emission tomography (PET) experiments on a selected compound.

Optimizing Boron Neutron Capture Therapy (BNCT) to Treat Cancer: An Updated Review on the Latest Developments on Boron Compounds and Strategies

“…Several of the abovementioned discussed developments on new boron compounds have been modified to be useful as theranostic compounds, e.g., [ 102 , 118 ]. Apart from these, more examples can be found in the literature although they have not been tested in BNCT radiobiological studies yet (e.g., [ 141 , 142 , 143 , 144 ]).…”

“…Preliminary results indicate a positive step forward toward optimizing BNCT, however, when preparing on a larger scale (i.e., human beings) the compound appears to be quite toxic for clinical applications. The discovery of potential theranostic candidates for BNCT still poses a challenge for researchers [ 142 ].…”

The role of radiolabeling in BNCT tracers for enhanced dosimetry and treatment planning

“…Compound Glc1 (Figure 6D) was selected for 18 F radiolabeling and in vivo study. However, the radiolabeled precursor showed poor stability and low brain uptake as compared with 18 F-FDG and could not be further evaluated for BNCT [77].…”