title: Monoclonal antibody and F(ab')2 fragment delivery to tumor in patients with glioma: comparison of intracarotid and intravenous administration.
abstract: Non-i.v. delivery of radiolabeled monoclonal antibodies (MAbs) has been shown to increase tumor uptake and decrease dose to normal tissues. In this study, we have examined the potential advantage of intracarotid (i.c.) versus i.v. administration for the delivery of an intact MAb and a F(ab')2 fragment to tumor in patients with gliomas. Three patients received 10-50 mg of 81C6 IgG2b, a MAb reactive with the glioma-associated extracellular matrix antigen tenascin, and three received 5-20 mg of the F(ab')2 fragment of Mel-14, which is reactive with gliomas and melanomas. Paired-injection protocols, in which one-half of the MAb was labeled with 131I and administered by i.c. injection, and one-half was labeled with 125I and simultaneously administered by i.v. injection, were used. For both 81C6 IgG2b and Mel-14 (Fab')2, no differences in blood clearance half-times or urinary excretion rates of radioiodine were observed between i.c.- and i.v.-administered activity. Analysis of biopsy samples revealed i.c.:i.v. uptake ratios of 1.02 +/- 0.04, 0.95 +/- 0.03, and 1.03 +/- 0.05 for the accumulation of 81C6 IgG2b in temporalis muscle, normal brain, and glioma, respectively. Similarly, the i.c.:i.v. uptake ratios for Mel-14 F(ab')2 in these tissues were 0.98 +/- 0.04 (SD), 1.00 +/- 0.05, and 1.04 +/- 0.05. When the differences in percentage of injected dose/g uptake after i.c. and i.v. administration were compared, no statistically significant advantage for i.c. delivery was seen (P = 0.22-0.61). These data indicate that i.c. administration of MAb 81C6 IgG2b and Mel-14 F(ab')2 fragments offers no delivery advantage to offset the small but finite risk involved in cannulation and injection of the internal carotid artery.
authors.affiliation: Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710.
authors.forename: M R
authors.initials: MR
authors.lastname: Zalutsky
authors.forename: R P
authors.initials: RP
authors.lastname: Moseley
authors.forename: J C
authors.initials: JC
authors.lastname: Benjamin
authors.forename: E V
authors.initials: EV
authors.lastname: Colapinto
authors.forename: G N
authors.initials: GN
authors.lastname: Fuller
authors.forename: H P
authors.initials: HP
authors.lastname: Coakham
authors.forename: D D
authors.initials: DD
authors.lastname: Bigner
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D002339:Carotid Arteries; D005909:Glioblastoma / Q000000981:diagnostic imaging / Q000378:metabolism*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000008:administration & dosage* / Q000493:pharmacokinetics; D007269:Injections, Intra-Arterial; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D009132:Muscles / Q000378:metabolism; D011877:Radionuclide Imaging
chemical_list: D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes