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Quantitative Tissue Pharmacokinetics and EPR Effect of AGuIX Nanoparticles: A Multimodal Imaging Study in an Orthotopic Glioblastoma Rat Model and Healthy Macaque
Author(s) -
Tran VuLong,
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
Publication year - 2021
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.202100656
Subject(s) - in vivo , glioblastoma , gadolinium , magnetic resonance imaging , radiation therapy , positron emission tomography , pharmacokinetics , brain tumor , in vitro , u87 , biomedical engineering , materials science , cancer research , nuclear medicine , medicine , pathology , chemistry , pharmacology , radiology , biology , biochemistry , microbiology and biotechnology , metallurgy
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.