Yttrium-90 radioembolization as a possible new treatment for brain cancer: proof of concept and safety analysis in a canine model

Abstract

Purpose

To evaluate the safety, feasibility, and preliminary efficacy of yttrium-90 ( ⁹⁰Y) radioembolization (RE) as a minimally invasive treatment in a canine model with presumed spontaneous brain cancers.

Materials

Three healthy research dogs (R1–R3) and five patient dogs with spontaneous intra-axial brain masses (P1–P5) underwent cerebral artery RE with ⁹⁰Y glass microspheres (TheraSphere). ⁹⁰Y-RE was performed on research dogs from the unilateral internal carotid artery (ICA), middle cerebral artery (MCA), and posterior cerebral artery (PCA) while animals with brain masses were treated from the ICA. Post-treatment ⁹⁰Y PET/CT was performed along with serial neurological exams by a veterinary neurologist. One month after treatment, research dogs were euthanized and the brains were extracted and sent for microdosimetric and histopathologic analyses. Patient dogs received post-treatment MRI at 1-, 3-, and 6-month intervals with long-term veterinary follow-up.

Results

The average absorbed dose to treated tissue in R1–R3 was 14.0, 30.9, and 73.2 Gy, respectively, with maximum doses exceeding 1000 Gy. One month after treatment, research dog pathologic analysis revealed no evidence of cortical atrophy and rare foci consistent with chronic infarcts, e.g., < 2-mm diameter. Absorbed doses to masses in P1–P5 were 45.5, 57.6, 58.1, 45.4, and 64.1 Gy while the dose to uninvolved brain tissue was 15.4, 27.6, 19.2, 16.7, and 33.3 G, respectively. Among both research and patient animals, 6 developed acute neurologic deficits following treatment. However, in all surviving dogs, the deficits were transient resolving between 7 and 33 days post-therapy. At 1 month post-therapy, patient animals showed a 24–94% reduction in mass volume with partial response in P1, P3, and P4 at 6 months post-treatment. While P2 initially showed a response, by 5 months, the mass had advanced beyond pre-treatment size, and the dog was euthanized.

Conclusion

This proof of concept demonstrates the technical feasibility and safety of ⁹⁰Y-RE in dogs, while preliminary, initial data on the efficacy of ⁹⁰Y-RE as a potential treatment for brain cancer is encouraging.