4.5 Article

Convection-enhanced delivery of cetuximab conjugated iron-oxide nanoparticles for treatment of spontaneous canine intracranial gliomas

Journal

JOURNAL OF NEURO-ONCOLOGY
Volume 137, Issue 3, Pages 653-663

Publisher

SPRINGER
DOI: 10.1007/s11060-018-2764-1

Keywords

Iron-oxide nanoparticles; Convection-enhanced delivery; Magnetic nanoparticles; Canine gliomas; Epidermal growth factor receptor (EGFR); Cetuximab

Funding

  1. American Kennel Club Canine Health Foundation
  2. NIH [NS053454, P50CA128301-01A10003]
  3. Georgia Cancer Coalition, Distinguished Cancer Clinicians and Scientists Program
  4. Dana Foundation
  5. Boo Radley Foundation
  6. UGA clinical research grants

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Cetuximab conjugated iron-oxide nanoparticles (cetuximab-IONPs) have shown both in-vitro and in-vivo anti-tumor efficacy against gliomas. The purpose of this pilot study was to evaluate the safety and potential efficacy of cetuximab-IONPs for treatment of spontaneously occurring intracranial gliomas in canines after convection-enhanced delivery (CED). The use of CED allowed for direct infusion of the cetuximab-IONPs both intratumorally and peritumorally avoiding the blood brain barrier (BBB) and limiting systemic effects. A total of eight dogs participated in the study and only two developed mild post-operative complications, which resolved with medical therapy. All canines underwent a single CED treatment of the cetuximab-IONPs over 3 days and did not receive any further adjuvant treatments. Volumetric analysis showed a median reduction in tumor size of 54.9% by MRI at 1-month (4-6 weeks) follow-up. Five dogs were euthanized due to recurrence of neurological signs other than seizures, two due to recurrent seizures, and one dog died in his sleep. Median survival time after surgery was 248 days (mean 367 days).

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