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

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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

  1. GE 3.0T Signa HDx; GE Healthcare, Milwaukee, WI.

  2. 3.0T Siemens Skyra.

  3. Siemens Symphony, TIM technology.

  4. Butorphanol tartrate; Torbugesic®, Fort Dodge, Fort Dodge, IA.

  5. Diazepam, Valium®; Hospira, Lakeforest, IL.

  6. Atropine sulfate; Med Pharmex, Pomona, CA.

  7. Glycopyrrolate; Baxter Healthcare Corp., Deerfield, IL.

  8. PropoFlo; Abbott Laboratories, North Chicago, IL.

  9. Isoflurane, MDI, Boise, ID.

  10. Gadopentetate dimeglumine, Magnevist®; Bayer HealthCare Pharmaceuticals, Wayne, NJ.

  11. Medtronic, Inc., Minneapolis, MN.

  12. See footnote 11.

  13. See footnote 11.

  14. OsiriX 3.6, Pixmeo, Bernex, Switzerland.

  15. See footnote 14

  16. See footnote 14

  17. Rabbit anti-olig2; GeneTex, Irvine, CA.

  18. Mouse anti-GFAP, Biogenex, San Ramon, CA.

  19. Mouse anti-EGFR, Lifespan Biosciences.

  20. Biotinylated secondary antibodies, Vector Laboratories, Burlingame, CA.

  21. A streptavidin-HRP conjugated label, Biocare Medical, LLC, Concord, CA.

  22. DAB, DAKO, Carpinteria, CA.

  23. Isotype rabbit or mouse control serum, Biocare Medical, LLC, Concord, CA.

References

  1. Snyder JM, Shofer FS, Van Winkle TJ, Massicotte C (2006) Canine intracranial primary neoplasia: 173 cases (1986–2003). J Vet Intern Med 20:669–675

    PubMed  Google Scholar 

  2. Song RB, Vite CH, Bradley CW, Cross JR (2013) Postmortem evaluation of 435 cases of intracranial neoplasia in dogs and relationship of neoplasm with breed, age, and body weight. J Vet Intern Med 27:1143–1152. https://doi.org/10.1111/jvim.12136

    Article  CAS  PubMed  Google Scholar 

  3. Dolecek TA, Propp JM, Stroup NE, Kruchko C (2012) CBTRUS statistical report: primary brain and central nervous system tumors diagnosed in the United States in 2005–2009. Neuro Oncol 14(Suppl 5): v1–v49. https://doi.org/10.1093/neuonc/nos218

    Article  PubMed  PubMed Central  Google Scholar 

  4. Ohgaki H, Dessen P, Jourde B, Horstmann S, Nishikawa T, Di Patre PL, Burkhard C, Schuler D, Probst-Hensch NM, Maiorka PC, Baeza N, Pisani P, Yonekawa Y, Yasargil MG, Lutolf UM, Kleihues P (2004) Genetic pathways to glioblastoma: a population-based study. Cancer Res 64:6892–6899. https://doi.org/10.1158/0008-5472.CAN-04-1337

    Article  CAS  PubMed  Google Scholar 

  5. Hu H, Barker A, Harcourt-Brown T, Jeffery N (2015) Systematic review of brain tumor treatment in dogs. J Vet Intern Med 29:1456–1463. https://doi.org/10.1111/jvim.13617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Rossmeisl JH, Duncan RB, Huckle WR, Troy GC (2007) Expression of vascular endothelial growth factor in tumors and plasma from dogs with primary intracranial neoplasms. Am J Vet Res 68:1239–1245. https://doi.org/10.2460/ajvr.68.11.1239

    Article  CAS  PubMed  Google Scholar 

  7. Dickinson PJ, LeCouteur RA, Higgins RJ, Bringas JR, Larson RF, Yamashita Y, Krauze MT, Forsayeth J, Noble CO, Drummond DC, Kirpotin DB, Park JW, Berger MS, Bankiewicz KS (2010) Canine spontaneous glioma: a translational model system for convection-enhanced delivery. Neuro Oncol 12:928–940. https://doi.org/10.1093/neuonc/noq046

    Article  PubMed  PubMed Central  Google Scholar 

  8. Stoica G, Kim HT, Hall DG, Coates JR (2004) Morphology, immunohistochemistry, and genetic alterations in dog astrocytomas. Vet Pathol 41:10–19. https://doi.org/10.1354/vp.41-1-10

    Article  CAS  PubMed  Google Scholar 

  9. Chakravarti A, Dicker A, Mehta M (2004) The contribution of epidermal growth factor receptor (EGFR) signaling pathway to radioresistance in human gliomas: a review of preclinical and correlative clinical data. Int J Radiat Oncol Biol Phys 58:927–931. https://doi.org/10.1016/j.ijrobp.2003.09.092

    Article  CAS  PubMed  Google Scholar 

  10. Sathornsumetee S, Rich JN (2008) Designer therapies for glioblastoma multiforme. Ann N Y Acad Sci 1142:108–132. https://doi.org/10.1196/annals.1444.009

    Article  CAS  PubMed  Google Scholar 

  11. Zhang X, Zhang W, Cao WD, Cheng G, Zhang YQ (2012) Glioblastoma multiforme: Molecular characterization and current treatment strategy (review). Exp Ther Med 3:9–14. https://doi.org/10.3892/etm.2011.367

    Article  PubMed  Google Scholar 

  12. Boudreau CE, York D, Higgins RJ, LeCouteur RA, Dickinson PJ (2017) Molecular signalling pathways in canine gliomas. Vet Comp Oncol 15:133–150. https://doi.org/10.1111/vco.12147

    Article  CAS  PubMed  Google Scholar 

  13. Dickinson PJ (2014) Advances in diagnostic and treatment modalities for intracranial tumors. J Vet Intern Med 28:1165–1185. https://doi.org/10.1111/jvim.12370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Higgins RJ, Dickinson PJ, LeCouteur RA, Bollen AW, Wang H, Wang H, Corely LJ, Moore LM, Zang W, Fuller GN (2010) Spontaneous canine gliomas: overexpression of EGFR, PDGFRalpha and IGFBP2 demonstrated by tissue microarray immunophenotyping. J Neuro-oncol 98:49–55. https://doi.org/10.1007/s11060-009-0072-5

    Article  CAS  Google Scholar 

  15. Debinski W, Dickinson P, Rossmeisl JH, Robertson J, Gibo DM (2013) New agents for targeting of IL-13RA2 expressed in primary human and canine brain tumors. PLoS ONE 8:e77719. https://doi.org/10.1371/journal.pone.0077719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. York D, Sproul CD, Chikere N, Dickinson PJ, Angelastro JM (2017) Expression and targeting of transcription factor ATF5 in dog gliomas. Vet Comp Oncol. https://doi.org/10.1111/vco.12317

    Google Scholar 

  17. Dickinson PJ, Roberts BN, Higgins RJ, Leutenegger CM, Bollen AW, Kass PH, LeCouteur RA (2006) Expression of receptor tyrosine kinases VEGFR-1 (FLT-1), VEGFR-2 (KDR), EGFR-1, PDGFRalpha and c-Met in canine primary brain tumours. Vet Comp Oncol 4:132–140. https://doi.org/10.1111/j.1476-5829.2006.00101.x

    Article  CAS  PubMed  Google Scholar 

  18. Neyns B, Sadones J, Joosens E, Bouttens F, Verbeke L, Baurain JF, D’Hondt L, Strauven T, Chaskis C, In’t Veld P, Michotte A, De Greve J (2009) Stratified phase II trial of cetuximab in patients with recurrent high-grade glioma. Ann Oncol 20: 1596–1603. https://doi.org/10.1093/annonc/mdp032

    Article  CAS  PubMed  Google Scholar 

  19. Dunn IF, Heese O, Black PM (2000) Growth factors in glioma angiogenesis: FGFs, PDGF, EGF, and TGFs. J Neuro-oncol 50:121–137

    Article  CAS  Google Scholar 

  20. Wong AJ, Bigner SH, Bigner DD, Kinzler KW, Hamilton SR, Vogelstein B (1987) Increased expression of the epidermal growth factor receptor gene in malignant gliomas is invariably associated with gene amplification. Proc Natl Acad Sci USA 84:6899–6903

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Smith JS, Tachibana I, Passe SM, Huntley BK, Borell TJ, Iturria N, O’Fallon JR, Schaefer PL, Scheithauer BW, James CD, Buckner JC, Jenkins RB (2001) PTEN mutation, EGFR amplification, and outcome in patients with anaplastic astrocytoma and glioblastoma multiforme. J Natl Cancer Inst 93:1246–1256

    Article  CAS  PubMed  Google Scholar 

  22. Cancer Genome Atlas Research Network (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455: 1061–1068. https://doi.org/10.1038/nature07385

    Article  Google Scholar 

  23. Verhaak RG, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD, Miller CR, Ding L, Golub T, Mesirov JP, Alexe G, Lawrence M, O’Kelly M, Tamayo P, Weir BA, Gabriel S, Winckler W, Gupta S, Jakkula L, Feiler HS, Hodgson JG, James CD, Sarkaria JN, Brennan C, Kahn A, Spellman PT, Wilson RK, Speed TP, Gray JW, Meyerson M, Getz G, Perou CM, Hayes DN, Cancer Genome Atlas Research Network (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17:98–110. https://doi.org/10.1016/j.ccr.2009.12.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Jutten B, Dubois L, Li Y, Aerts H, Wouters BG, Lambin P, Theys J, Lammering G (2009) Binding of cetuximab to the EGFRvIII deletion mutant and its biological consequences in malignant glioma cells. Radiother Oncol 92:393–398. https://doi.org/10.1016/j.radonc.2009.06.021

    Article  CAS  PubMed  Google Scholar 

  25. Combs SE, Heeger S, Haselmann R, Edler L, Debus J, Schulz-Ertner D (2006) Treatment of primary glioblastoma multiforme with cetuximab, radiotherapy and temozolomide (GERT)—phase I/II trial: study protocol. BMC Cancer 6:133. https://doi.org/10.1186/1471-2407-6-133

    Article  PubMed  PubMed Central  Google Scholar 

  26. Singer J, Weichselbaumer M, Stockner T, Mechtcheriakova D, Sobanov Y, Bajna E, Wrba F, Horvat R, Thalhammer JG, Willmann M, Jensen-Jarolim E (2012) Comparative oncology: ErbB-1 and ErbB-2 homologues in canine cancer are susceptible to cetuximab and trastuzumab targeting. Mol Immunol 50:200–209. https://doi.org/10.1016/j.molimm.2012.01.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Baumann M, Krause M (2004) Targeting the epidermal growth factor receptor in radiotherapy: radiobiological mechanisms, preclinical and clinical results. Radiother Oncol 72:257–266. https://doi.org/10.1016/j.radonc.2004.07.007

    Article  CAS  PubMed  Google Scholar 

  28. Hasselbalch B, Lassen U, Hansen S, Holmberg M, Sorensen M, Kosteljanetz M, Broholm H, Stockhausen MT, Poulsen HS (2010) Cetuximab, bevacizumab, and irinotecan for patients with primary glioblastoma and progression after radiation therapy and temozolomide: a phase II trial. Neuro Oncol 12:508–516. https://doi.org/10.1093/neuonc/nop063

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Belda-Iniesta C, Carpeno Jde C, Saenz EC, Gutierrez M, Perona R, Baron MG (2006) Long term responses with cetuximab therapy in glioblastoma multiforme. Cancer Biol Ther 5:912–914

    Article  CAS  PubMed  Google Scholar 

  30. Hadjipanayis CG, Machaidze R, Kaluzova M, Wang L, Schuette AJ, Chen H, Wu X, Mao H (2010) EGFRvIII antibody-conjugated iron oxide nanoparticles for magnetic resonance imaging-guided convection-enhanced delivery and targeted therapy of glioblastoma. Cancer Res 70:6303–6312. https://doi.org/10.1158/0008-5472.CAN-10-1022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Liu HL, Hua MY, Yang HW, Huang CY, Chu PC, Wu JS, Tseng IC, Wang JJ, Yen TC, Chen PY, Wei KC (2010) Magnetic resonance monitoring of focused ultrasound/magnetic nanoparticle targeting delivery of therapeutic agents to the brain. Proc Natl Acad Sci USA 107:15205–15210. https://doi.org/10.1073/pnas.1003388107

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kaluzova M, Bouras A, Machaidze R, Hadjipanayis CG (2015) Targeted therapy of glioblastoma stem-like cells and tumor non-stem cells using cetuximab-conjugated iron-oxide nanoparticles. Oncotarget 6:8788–8806. https://doi.org/10.18632/oncotarget.3554

    Article  PubMed  PubMed Central  Google Scholar 

  33. Barua NU, Gill SS, Love S (2013) Convection-enhanced drug delivery to the brain: therapeutic potential and neuropathological considerations. Brain Pathology. https://doi.org/10.1111/bpa.12082

    PubMed  Google Scholar 

  34. Yun J, Rothrock RJ, Canoll P, Bruce JN (2013) Convection-enhanced delivery for targeted delivery of antiglioma agents: the translational experience. J Drug Deliv 2013:107573. https://doi.org/10.1155/2013/107573

    Article  PubMed  PubMed Central  Google Scholar 

  35. Saito R, Tominaga T (2012) Convection-enhanced delivery: from mechanisms to clinical drug delivery for diseases of the central nervous system. Neurol Med Chir 52:531–538

    Article  Google Scholar 

  36. Dickinson PJ, LeCouteur RA, Higgins RJ, Bringas JR, Roberts B, Larson RF, Yamashita Y, Krauze M, Noble CO, Drummond D, Kirpotin DB, Park JW, Berger MS, Bankiewicz KS (2008) Canine model of convection-enhanced delivery of liposomes containing CPT-11 monitored with real-time magnetic resonance imaging: laboratory investigation. J Neurosurg 108:989–998. https://doi.org/10.3171/JNS/2008/108/5/0989

    Article  CAS  PubMed  Google Scholar 

  37. Platt S, Nduom E, Kent M, Freeman C, Machaidze R, Kaluzova M, Wang L, Mao H, Hadjipanayis CG (2012) Canine model of convection-enhanced delivery of cetuximab-conjugated iron-oxide nanoparticles monitored with magnetic resonance imaging. Clin Neurosurg 59:107–113. https://doi.org/10.1227/NEU.0b013e31826989ef

    Article  PubMed  PubMed Central  Google Scholar 

  38. Young BD, Levine JM, Porter BF, Chen-Allen AV, Rossmeisl JH, Platt SR, Kent M, Fosgate GT, Schatzberg SJ (2011) Magnetic resonance imaging features of intracranial astrocytomas and oligodendrogliomas in dogs. Vet Radiol Ultrasound 52:132–141. https://doi.org/10.1111/j.1740-8261.2010.01758.x

    Article  PubMed  Google Scholar 

  39. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK, Burger PC, Jouvet A, Scheithauer BW, Kleihues P (2007) The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol 114:97–109. https://doi.org/10.1007/s00401-007-0243-4

    Article  PubMed  PubMed Central  Google Scholar 

  40. Martens T, Laabs Y, Gunther HS, Kemming D, Zhu Z, Witte L, Hagel C, Westphal M, Lamszus K (2008) Inhibition of glioblastoma growth in a highly invasive nude mouse model can be achieved by targeting epidermal growth factor receptor but not vascular endothelial growth factor receptor-2. Clin Cancer Res 14:5447–5458. https://doi.org/10.1158/1078-0432.CCR-08-0147

    Article  CAS  PubMed  Google Scholar 

  41. Diaz Miqueli A, Rolff J, Lemm M, Fichtner I, Perez R, Montero E (2009) Radiosensitisation of U87MG brain tumours by anti-epidermal growth factor receptor monoclonal antibodies. Br J Cancer 100:950–958. https://doi.org/10.1038/sj.bjc.6604943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Eller JL, Longo SL, Hicklin DJ, Canute GW (2002) Activity of anti-epidermal growth factor receptor monoclonal antibody C225 against glioblastoma multiforme. Neurosurgery 51:1005–1013 (discussion 1013-1004)

    PubMed  Google Scholar 

  43. Eller JL, Longo SL, Kyle MM, Bassano D, Hicklin DJ, Canute GW (2005) Anti-epidermal growth factor receptor monoclonal antibody cetuximab augments radiation effects in glioblastoma multiforme in vitro and in vivo. Neurosurgery 56:155–162 (discussion 162)

    Article  PubMed  Google Scholar 

  44. Chakraborty S, Filippi CG, Wong T, Ray A, Fralin S, Tsiouris AJ, Praminick B, Demopoulos A, McCrea HJ, Bodhinayake I, Ortiz R, Langer DJ, Boockvar JA (2016) Superselective intraarterial cerebral infusion of cetuximab after osmotic blood/brain barrier disruption for recurrent malignant glioma: phase I study. J Neuro-oncol 128:405–415. https://doi.org/10.1007/s11060-016-2099-8

    Article  CAS  Google Scholar 

  45. Garrett CR, Eng C (2011) Cetuximab in the treatment of patients with colorectal cancer. Expert Opin Biol Ther 11:937–949. https://doi.org/10.1517/14712598.2011.582464

    Article  CAS  PubMed  Google Scholar 

  46. Hebbar M, Wacrenier A, Desauw C, Romano O, Cattan S, Triboulet JP, Pruvot FR (2006) Lack of usefulness of epidermal growth factor receptor expression determination for cetuximab therapy in patients with colorectal cancer. Anticancer Drugs 17:855–857. https://doi.org/10.1097/01.cad.0000217425.44584.9f

    Article  CAS  PubMed  Google Scholar 

  47. Chung KY, Shia J, Kemeny NE, Shah M, Schwartz GK, Tse A, Hamilton A, Pan D, Schrag D, Schwartz L, Klimstra DS, Fridman D, Kelsen DP, Saltz LB (2005) Cetuximab shows activity in colorectal cancer patients with tumors that do not express the epidermal growth factor receptor by immunohistochemistry. J Clin Oncol 23:1803–1810. https://doi.org/10.1200/JCO.2005.08.037

    Article  CAS  PubMed  Google Scholar 

  48. Sandhiya S, Dkhar SA, Surendiran A (2009) Emerging trends of nanomedicine–an overview. Fundam Clin Pharmacol 23:263–269. https://doi.org/10.1111/j.1472-8206.2009.00692.x

    Article  CAS  PubMed  Google Scholar 

  49. Mahmoudi K, Hadjipanayis CG (2014) The application of magnetic nanoparticles for the treatment of brain tumors. Front Chem 2:109. https://doi.org/10.3389/fchem.2014.00109

    Article  PubMed  PubMed Central  Google Scholar 

  50. Wankhede M, Bouras A, Kaluzova M, Hadjipanayis CG (2012) Magnetic nanoparticles: an emerging technology for malignant brain tumor imaging and therapy. Expert Rev Clin Pharmacol 5:173–186. https://doi.org/10.1586/ecp.12.1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Bouras A, Kaluzova M, Hadjipanayis CG (2015) Radiosensitivity enhancement of radioresistant glioblastoma by epidermal growth factor receptor antibody-conjugated iron-oxide nanoparticles. J Neuro-oncol 124:13–22. https://doi.org/10.1007/s11060-015-1807-0

    Article  CAS  Google Scholar 

  52. Sampson JH, Archer G, Pedain C, Wembacher-Schroder E, Westphal M, Kunwar S, Vogelbaum MA, Coan A, Herndon JE, Raghavan R, Brady ML, Reardon DA, Friedman AH, Friedman HS, Rodriguez-Ponce MI, Chang SM, Mittermeyer S, Croteau D, Puri RK, Investigators PT (2010) Poor drug distribution as a possible explanation for the results of the PRECISE trial. J Neurosurg 113:301–309. https://doi.org/10.3171/2009.11.JNS091052

    Article  PubMed  Google Scholar 

  53. Lipsitz D, Higgins RJ, Kortz GD, Dickinson PJ, Bollen AW, Naydan DK, LeCouteur RA (2003) Glioblastoma multiforme: clinical findings, magnetic resonance imaging, and pathology in five dogs. Vet Pathol 40:659–669. https://doi.org/10.1354/vp.40-6-659

    Article  CAS  PubMed  Google Scholar 

  54. Dolera M, Malfassi L, Bianchi C, Carrara N, Finesso S, Marcarini S, Mazza G, Pavesi S, Sala M, Urso G (2017) Frameless stereotactic radiotherapy alone and combined with temozolomide for presumed canine gliomas. Vet Comp Oncol. https://doi.org/10.1111/vco.12316

    PubMed  Google Scholar 

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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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Authors and Affiliations

  1. Veterinary Specialty Care, 985 Johnnie Dodds Blvd, Mount Pleasant, SC, 29464, USA

    A. Courtenay Freeman

  2. Department of Small Animal Medicine & Surgery, College of Veterinary Medicine, University of Georgia, 2200 College Station Rd, Athens, GA, 30602, USA

    Simon R. Platt, M. Kent & Kelsey Robinson

  3. Department of Veterinary Biosciences and Diagnostic Imaging, College of Veterinary Medicine, University of Georgia, 501 DW Brooks Drive, Athens, GA, 30602, USA

    Shannon Holmes

  4. Department of Pathology, College of Veterinary Medicine, University of Georgia, 501 DW Brooks Drive, Athens, GA, 30602, USA

    Elizabeth Howerth

  5. Veterinary Specialty & Emergency Center, 1114 South Front Street, Philadelphia, PA, 19056, USA

    Joe Eagleson

  6. Brain Tumor Nanotechnology Laboratory, Department of Neurosurgery, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, New York, NY, 10029, USA

    Alexandros Bouras & Constantinos G. Hadjipanayis

  7. Department of Neurosurgery, Emory University School of Medicine, Winship Cancer Institute of Emory University, Atlanta, GA, 30322, USA

    Milota Kaluzova

  8. Department of Neurosurgery, Mount Sinai Beth Israel, 10 Union Square East, New York, NY, 10003, USA

    Constantinos G. Hadjipanayis

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  1. A. Courtenay Freeman
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  10. Constantinos G. Hadjipanayis
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Correspondence to A. Courtenay Freeman or Constantinos G. Hadjipanayis.

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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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