23.10.2023 | Research Article
Toward a Nanoencapsulated EPR Imaging Agent for Clinical Use
verfasst von:
Rhia M. Martin, Samantha Diaz, Martin Poncelet, Benoit Driesschaert, Eugene Barth, Mrignayani Kotecha, Boris Epel, Gareth R. Eaton, Joshua R. Biller
Erschienen in:
Molecular Imaging and Biology
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Abstract
Purpose
Progress toward developing a novel radiocontrast agent for determining pO2 in tumors in a clinical setting is described. The imaging agent is designed for use with electron paramagnetic resonance imaging (EPRI), in which the collision of a paramagnetic probe molecule with molecular oxygen causes a spectroscopic change which can be calibrated to give the real oxygen concentration in the tumor tissue.
Procedures
The imaging agent is based on a nanoscaffold of aluminum hydroxide (boehmite) with sizes from 100 to 200 nm, paramagnetic probe molecule, and encapsulation with a gas permeable, thin (10–20 nm) polymer layer to separate the imaging agent and body environment while still allowing O2 to interact with the paramagnetic probe. A specially designed deuterated Finland trityl (dFT) is covalently attached on the surface of the nanoparticle through 1,3-dipolar addition of the alkyne on the dFT with an azide on the surface of the nanoscaffold. This click-chemistry reaction affords 100% efficiency of the trityl attachment as followed by the complete disappearance of the azide peak in the infrared spectrum. The fully encapsulated, dFT-functionalized nanoparticle is referred to as RADI-Sense.
Results
Side-by-side in vivo imaging comparisons made in a mouse model made between RADI-Sense and free paramagnetic probe (OX-071) showed oxygen sensitivity is retained and RADI-Sense can create 3D pO2 maps of solid tumors
Conclusions
A novel encapsulated nanoparticle EPR imaging agent has been described which could be used in the future to bring EPR imaging for guidance of radiotherapy into clinical reality.