Pharmacokinetics and tumor localization of 131I-labeled anti-tenascin monoclonal antibody 81C6 in patients with gliomas and other intracranial malignancies.
We previously have reported that radioiodinated anti-tenascin monoclonal antibody 81C6 exhibits therapeutic potential against both s.c. and intracranial human glioma xenografts in athymic mice and rats. Herein we report the selective tumor localization of 131I-labeled 81C6 in patients with gliomas and other intracranial malignancies. Nine patients were simultaneously administered 5-50 mg of 131I-labeled 81C6 and 1-2 mg of 125I-labeled 45.6, an isotype-matched control monoclonal antibody. The blood clearance half-time for 81C6, normalized to that of 45.6 in the same patient, appeared to decrease with 81C6 protein dose. Gamma camera images obtained at 1 to 3 days exhibited increased uptake of 131I in regions corresponding to tumor with varying degrees of contrast to surrounding normal brain. Biopsy specimens of tumor and normal brain were obtained and analyzed histologically for tumor content. The average uptake of 81C6 in tumor ranged from 0.6 to 4.3 x 10(-3)% of the injected dose per gram. In patients receiving 20-50 mg of 81C6, the average tumor-to-normal-brain ratio was 25:1 with ratios as high as 200:1 seen in some samples. Localization indices were calculated by normalizing the uptake of 81C6 per gram tumor to the uptake of 81C6 per gram blood and dividing by the same ratio for 45.6 control monoclonal antibody. Localization indices for muscle and brain were about 1, in contrast to up to five for tumor. These studies demonstrate that the tumor uptake of 131I-labeled 81C6 in patients with gliomas and other intracranial malignancies is due to specific processes.
Zalutsky
M R
MR
Department of Radiology, Duke University Medical Center, Durham, North Carolina 27710.
Moseley
R P
RP
Coakham
H B
HB
Coleman
R E
RE
Bigner
D D
DD
D000911:Antibodies, Monoclonal / Q000032:analysis*; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology*; D005910:Glioma / Q000000981:diagnostic imaging / Q000276:immunology*; D006207:Half-Life; D006801:Humans; D007457:Iodine Radioisotopes; D008657:Metabolic Clearance Rate; D009363:Neoplasm Proteins / Q000276:immunology*; D011506:Proteins / Q000276:immunology*; D011877:Radionuclide Imaging; D019063:Tenascin
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D009363:Neoplasm Proteins; D011506:Proteins; D019063:Tenascin