Blood-brain barrier disruption and delivery of irinotecan in a rat model using a clinical transcranial MRI-guided focused ultrasound system.
Animals
Antineoplastic Agents
/ administration & dosage
Blood-Brain Barrier
Brain Edema
/ etiology
Brain Neoplasms
/ drug therapy
Female
Glioma
/ drug therapy
Irinotecan
/ administration & dosage
Magnetic Resonance Imaging
/ methods
Male
Microbubbles
Pilot Projects
Prodrugs
/ administration & dosage
Purpura
/ etiology
Random Allocation
Rats
Rats, Inbred F344
Rats, Sprague-Dawley
Sonication
/ adverse effects
Topoisomerase I Inhibitors
/ administration & dosage
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
29 05 2020
29 05 2020
Historique:
received:
11
12
2019
accepted:
17
03
2020
entrez:
31
5
2020
pubmed:
31
5
2020
medline:
15
12
2020
Statut:
epublish
Résumé
We investigated controlled blood-brain barrier (BBB) disruption using a low-frequency clinical transcranial MRI-guided focused ultrasound (TcMRgFUS) device and evaluated enhanced delivery of irinotecan chemotherapy to the brain and a rat glioma model. Animals received three weekly sessions of FUS, FUS and 10 mg/kg irinotecan, or irinotecan alone. In each session, four volumetric sonications targeted 36 locations in one hemisphere. With feedback control based on recordings of acoustic emissions, 98% of the sonication targets (1045/1071) reached a pre-defined level of acoustic emission, while the probability of wideband emission (a signature for inertial cavitation) was than 1%. BBB disruption, evaluated by mapping the R1 relaxation rate after administration of an MRI contrast agent, was significantly higher in the sonicated hemisphere (P < 0.01). Histological evaluation found minimal tissue effects. Irinotecan concentrations in the brain were significantly higher (P < 0.001) with BBB disruption, but SN-38 was only detected in <50% of the samples and only with an excessive irinotecan dose. Irinotecan with BBB disruption did not impede tumor growth or increase survival. Overall these results demonstrate safe and controlled BBB disruption with a low-frequency clinical TcMRgFUS device. While irinotecan delivery to the brain was not neurotoxic, it did not improve outcomes in the F98 glioma model.
Identifiants
pubmed: 32472017
doi: 10.1038/s41598-020-65617-6
pii: 10.1038/s41598-020-65617-6
pmc: PMC7260193
doi:
Substances chimiques
Antineoplastic Agents
0
Prodrugs
0
Topoisomerase I Inhibitors
0
Irinotecan
7673326042
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
8766Subventions
Organisme : NCI NIH HHS
ID : P01 CA174645
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH116858
Pays : United States
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