Quantitative Tissue Pharmacokinetics and EPR Effect of AGuIX Nanoparticles: A Multimodal Imaging Study in an Orthotopic Glioblastoma Rat Model and Healthy Macaque. Issue 16 (1st July 2021)

• Record Type: Journal Article
• Authors: Tran, Vu‐Long; Lux, François; Tournier, Nicolas; Jego, Benoit; Maître, Xavier; Anisorac, Maria; Comtat, Claude; Jan, Sébastien; Selmeczi, Katalin; Evans, Michael J.; Tillement, Olivier; Kuhnast, Bertrand; Truillet, Charles
• Is Part Of: Advanced healthcare materials. Volume 10:Issue 16(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-07-01
• Subjects: EPR effects -- PET imaging -- radiolabeling; Biomedical materials -- Periodicals; 610.28
• DOI: 10.1002/adhm.202100656
• Languages: English
• ISSNs: 2192-2640

Abstract

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. Abstract : AGuIX nanoparticle is a promising tumor‐targeted enhancer for radiotherapy (RT). It is found that AGuIX can be directly 89 Zr‐radiolabeled without modifying its physicochemical structure to monitor its whole‐body pharmacokinetic and tumor uptake by positron emission tomography (PET) imaging. This dynamic imaging is crucial for fractionated radiation dose personalization. Labeled particles show particular prolonged retention in the tumor especially in necrosis, highly radioresistant areas.