Comparison of intratumoral bolus injection and convection-enhanced delivery of radiolabeled antitenascin monoclonal antibodies.
OBJECTIVE
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.
Sampson
John H
JH
Department of Surgery (Neurosurgery), Duke University Medical Center, Durham, North Carolina 27710, USA. john.sampson@duke.edu
Akabani
Gamal
G
Friedman
Allan H
AH
Bigner
Darell
D
Kunwar
Sandeep
S
Berger
Mitchel S
MS
Bankiewicz
Krystof S
KS
D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology / Q000601:surgery; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D016503:Drug Delivery Systems / Q000379:methods*; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007260:Infusion Pumps; D007457:Iodine Radioisotopes / Q000008:administration & dosage; D008279:Magnetic Resonance Imaging; D008845:Microinjections / Q000379:methods; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D013238:Stereotaxic Techniques / Q000295:instrumentation; D015996:Survival Rate; D019063:Tenascin / Q000276:immunology*; D015899:Tomography, Emission-Computed, Single-Photon; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D019063:Tenascin