Abstract
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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Notes
GE 3.0T Signa HDx; GE Healthcare, Milwaukee, WI.
3.0T Siemens Skyra.
Siemens Symphony, TIM technology.
Butorphanol tartrate; Torbugesic®, Fort Dodge, Fort Dodge, IA.
Diazepam, Valium®; Hospira, Lakeforest, IL.
Atropine sulfate; Med Pharmex, Pomona, CA.
Glycopyrrolate; Baxter Healthcare Corp., Deerfield, IL.
PropoFlo; Abbott Laboratories, North Chicago, IL.
Isoflurane, MDI, Boise, ID.
Gadopentetate dimeglumine, Magnevist®; Bayer HealthCare Pharmaceuticals, Wayne, NJ.
Medtronic, Inc., Minneapolis, MN.
See footnote 11.
See footnote 11.
OsiriX 3.6, Pixmeo, Bernex, Switzerland.
See footnote 14
See footnote 14
Rabbit anti-olig2; GeneTex, Irvine, CA.
Mouse anti-GFAP, Biogenex, San Ramon, CA.
Mouse anti-EGFR, Lifespan Biosciences.
Biotinylated secondary antibodies, Vector Laboratories, Burlingame, CA.
A streptavidin-HRP conjugated label, Biocare Medical, LLC, Concord, CA.
DAB, DAKO, Carpinteria, CA.
Isotype rabbit or mouse control serum, Biocare Medical, LLC, Concord, CA.
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Acknowledgements
The authors thank Ken Johnson with the Boo Radley Foundation, Wilder Grummon with Medtronics, the UGA Bioimaging Research Center, Lisa Reno, Tim Jarrett, Kim Mason, referral neurologists including Gillian Irving and Jason King.
Funding
Funding provided in part by American Kennel Club Canine Health Foundation, the NIH (NS053454; P50CA128301-01A10003), the Georgia Cancer Coalition, Distinguished Cancer Clinicians and Scientists Program, and the Dana Foundation, the Boo Radley Foundation, and UGA clinical research grants.
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Freeman, A.C., Platt, S.R., Holmes, S. et al. Convection-enhanced delivery of cetuximab conjugated iron-oxide nanoparticles for treatment of spontaneous canine intracranial gliomas. J Neurooncol 137, 653–663 (2018). https://doi.org/10.1007/s11060-018-2764-1
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DOI: https://doi.org/10.1007/s11060-018-2764-1