Comparison of intratumoral bolus injection and convection-enhanced delivery of radiolabeled antitenascin monoclonal antibodies

Neurosurg Focus. 2006 Apr 15;20(4):E14. doi: 10.3171/foc.2006.20.4.9.

Abstract

Objectives: Convection-enhanced delivery (CED) is a novel technique used to deliver agents to the brain parenchyma for treatment of neoplastic, infectious, and degenerative conditions. The purpose of this study was to determine if CED would provide a larger volume of distribution (Vd) of a radiolabeled monoclonal antibody (mAb) than a bolus injection.

Methods: Patients harboring a recurrent glioblastoma multiforme that reacted with the antitenascin mAb 81C6 during immunohistochemical analysis were randomized to receive an intratumoral injection of the human-murine chimeric mAb Ch81C6, which had been labeled with the 123I tracer. The mAb was administered by either a bolus injection or CED via a stereotactically placed catheter; between 48 and 72 hours later the mAb was again administered using the other technique. Injections of escalating doses of a 131I-labeled therapeutic mAb were then delivered using the technique shown to produce the largest Vd by single-photon emission computerized tomography.

Conclusions: Convection-enhanced delivery has enormous potential for administering drugs to sites within the central nervous system. For the relatively small volumes injected in this study, however, CED did not provide a significant increase in the Vd when compared with the bolus injection. Nevertheless, a clear cross-over effect was seen, which was probably related to the temporal proximity of the two infusions.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Monoclonal / administration & dosage*
  • Brain / diagnostic imaging
  • Brain / pathology
  • Brain / surgery
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / immunology
  • Dose-Response Relationship, Drug
  • Drug Administration Routes
  • Drug Delivery Systems / methods*
  • Glioblastoma / diagnostic imaging
  • Glioblastoma / drug therapy*
  • Glioblastoma / immunology
  • Humans
  • Immunotherapy / methods*
  • Infusion Pumps
  • Iodine Radioisotopes / administration & dosage
  • Magnetic Resonance Imaging
  • Microinjections / methods
  • Neoplasm Recurrence, Local / drug therapy
  • Stereotaxic Techniques / instrumentation
  • Survival Rate
  • Tenascin / immunology*
  • Tomography, Emission-Computed, Single-Photon
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Iodine Radioisotopes
  • Tenascin