Quantitative Tissue Pharmacokinetics and EPR Effect of AGuIX Nanoparticles: A Multimodal Imaging Study in an Orthotopic Glioblastoma Rat Model and Healthy Macaque.

Abstract

AGuIX are emerging radiosensitizing nanoparticles (NPs) for precision radiotherapy (RT) under clinical evaluation (Phase 2). Despite being accompanied by MRI thanks to the presence of gadolinium (Gd) at its surface, more sensitive and quantifiable imaging technique should further leverage the full potential of this technology. In this study, it is shown that ⁸⁹ Zr can be labeled on such NPs directly for positron emission tomography (PET) imaging with a simple and scalable method. The stability of such complexes is remarkable in vitro and in vivo. Using a glioblastoma orthotopic rat model, it is shown that injected ⁸⁹ Zr-AGuIX is detectable inside the tumor for at least 1 week. Interestingly, the particles seem to efficiently infiltrate the tumor even in necrotic areas, which places great hope for the treatment of radioresistant tumor. Lastly, the first PET/MR whole-body imaging is performed in non-human primate (NHP), which further demonstrates the translational potential of these bimodal NP.