Brain delivery enabled by transient blood-brain barrier disruption induced by regadenoson: a PET imaging study.

Autor:	Hosten B; Université Paris-Saclay, Inserm, CNRS, CEA, Laboratoire d'Imagerie Biomédicale Multimodale (BioMaps), Service Hospitalier Frédéric Joliot, Orsay, France.; INSERM UMR1144, Université Paris Cité, Paris, France., Goutal S; Université Paris-Saclay, Inserm, CNRS, CEA, Laboratoire d'Imagerie Biomédicale Multimodale (BioMaps), Service Hospitalier Frédéric Joliot, Orsay, France., Leterrier S; Université Paris-Saclay, Inserm, CNRS, CEA, Laboratoire d'Imagerie Biomédicale Multimodale (BioMaps), Service Hospitalier Frédéric Joliot, Orsay, France., Corvo C; Université Paris-Saclay, Inserm, CNRS, CEA, Laboratoire d'Imagerie Biomédicale Multimodale (BioMaps), Service Hospitalier Frédéric Joliot, Orsay, France., Breuil L; Université Paris-Saclay, Inserm, CNRS, CEA, Laboratoire d'Imagerie Biomédicale Multimodale (BioMaps), Service Hospitalier Frédéric Joliot, Orsay, France.; INSERM UMR1144, Université Paris Cité, Paris, France., Barret O; CEA, CNRS, Université Paris-Saclay, MIRCen, Laboratoire des Maladies Neurodégénératives, Fontenay-Aux-Roses, France., Specklin S; Université Paris-Saclay, Inserm, CNRS, CEA, Laboratoire d'Imagerie Biomédicale Multimodale (BioMaps), Service Hospitalier Frédéric Joliot, Orsay, France., Truillet C; Université Paris-Saclay, Inserm, CNRS, CEA, Laboratoire d'Imagerie Biomédicale Multimodale (BioMaps), Service Hospitalier Frédéric Joliot, Orsay, France., Tournier N; Université Paris-Saclay, Inserm, CNRS, CEA, Laboratoire d'Imagerie Biomédicale Multimodale (BioMaps), Service Hospitalier Frédéric Joliot, Orsay, France.
Jazyk:	angličtina
Zdroj:	Expert opinion on drug delivery [Expert Opin Drug Deliv] 2024 May; Vol. 21 (5), pp. 797-807. Date of Electronic Publication: 2024 Jun 20.
DOI:	10.1080/17425247.2024.2369765
Abstrakt:	Background: Regadenoson, an agonist of adenosine A2 receptors, enables transient blood-brain barrier (BBB) disruption. The relevance of regadenoson as a pharmacological strategy for brain delivery was investigated using in vivo PET imaging in rats. Research Design and Methods: Kinetic modeling of brain PET data was performed to estimate the impact of regadenoson (0.05 mg.kg ^-1 , i.v.) on BBB permeation compared with control rats ( n = 4-6 per group). Three radiolabeled compounds of different sizes, which do not cross the intact BBB, were tested. Results: Regadenoson significantly increased the BBB penetration (+116 ± 13%, p < 0.001) of [ ¹⁸ F]2-deoxy-2-fluoro-D-sorbitol ([ ¹⁸ F]FDS, MW = 183 Da), a small-molecule marker of BBB permeability. The magnitude of the effect was different across brain regions, with a maximum increase in the striatum. Recovery of BBB integrity was observed 30 min after regadenoson injection. Regadenoson also increased the brain penetration (+72 ± 45%, p < 0.05) of a radiolabeled nanoparticle [ ⁸⁹ Zr]AGuIX (MW = 9 kDa). However, the brain kinetics of a monoclonal antibody ([ ⁸⁹ Zr]mAb, MW = 150 kDa) remained unchanged ( p > 0.05). Conclusions: PET imaging showed the features and limitations of BBB disruption induced by regadenoson in terms of extent, regional distribution, and reversibility. Nevertheless, regadenoson enables the brain delivery of small molecules or nanoparticles in rats.
Databáze:	MEDLINE
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