1. Toward a Nanoencapsulated EPR Imaging Agent for Clinical Use.
- Author
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Martin RM, Diaz S, Poncelet M, Driesschaert B, Barth E, Kotecha M, Epel B, Eaton GR, and Biller JR
- Subjects
- Animals, Electron Spin Resonance Spectroscopy methods, Mice, Humans, Contrast Media chemistry, Neoplasms diagnostic imaging, Nanoparticles chemistry, Oxygen chemistry
- Abstract
Purpose: Progress toward developing a novel radiocontrast agent for determining pO
2 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., (© 2023. The Author(s), under exclusive licence to World Molecular Imaging Society.)- Published
- 2024
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