Abstract
1230
Objectives Glioblastoma (GBM) is a high-grade astrocytoma with a dismal prognosis. A major challenge in treating GBM has been difficulty delivering therapeutics across the blood brain barrier (BBB). External beam radiation therapy has been shown to be an effective means of permeabilizing the BBB. We therefore examined the effects of alpha-particle emitter therapy on BBB permeability.
Methods Nanoparticles radiolabeled with 225Ac were injected intracranially into C57BL/6 mice and RH-Foxn1rnu rats (~1µ/animal). BBB leakage was measured using contrast-enhanced MRI after 48 hours and Even’ blue dye after 2, 5 and 10 days. Histological integrity was examined using IHC and H&E staining.
Results Animals demonstrated contrast extravasation on MRI in the area of α-particle infusion, manifesting BBB permeability. Longer-term studies in mice demonstrated permeability of the BBB to systemically administered Evan’s blue dye at 2, 5 and 10 days post infusion. H&E staining and IHC showed no visible damage in regions of BBB opening.
Conclusions Based on our findings, α-particle therapy can potentially be exploited to permeabilize the BBB for systemically administered therapies.
Research Support Work was supported by a Mentored Research Scholar Grant #124443-MRSG-13-121-01-CDD (Mintz) from the American Cancer Society.