title: Improving radioimmunotargeting of tumors: the impact of preloading unlabeled L6 monoclonal antibody on the biodistribution of 125I-L6 in rats.
abstract: In the radioimmunotherapy of malignancies the uptake of monoclonal antibodies (MoAb) is commonly low in tumors compared with normal tissue. Several methods have been suggested to increase the tumor-to-normal tissue (T/N) ratio. In this study we have investigated the biodistribution of different amounts of 125I-L6-biotin MoAb in combination with a preload of unlabeled L6 MoAb. Nude rats were injected with 50 micrograms or 250 micrograms of unlabeled L6 24 hours prior to the injection of 10 micrograms, 50 micrograms or 250 micrograms of 125I-L6, antipancarcinoma MoAb. Dissections were performed 24 hours after the injection of radiolabeled MoAb. The maximal enhancement of tumor uptake with simultaneously decreased uptake in normal tissues was with 250 micrograms of 125I-L6 preceded by a preload of 50 micrograms unlabeled L6. Mean T/N ratios were improved by a factor of 2.9 for bone marrow, 3.4 for liver, 3.7 for lungs and 2.3 for kidneys as compared with the corresponding controls. This study demonstrated that preinjection of optimal amounts of unlabeled L6 MoAb may increase the uptake of 125I-L6 by tumor and improve the T/N ratios. Based on present data, preloading with unlabeled MoAb should be considered in future clinical studies with immunoconjugates to improve the radioimmunotargeting of tumors. It is essential to titrate an appropriate amount of the preload, thus avoiding possible tumor antigen saturation of unlabeled MoAbs but simultaneously decreasing the uptake of subsequently injected radiolabeled MoAb in normal tissues.
authors.affiliation: Department of Oncology, Lund University, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Garkavij
authors.forename: J
authors.initials: J
authors.lastname: Tennvall
authors.forename: S E
authors.initials: SE
authors.lastname: Strand
authors.forename: K
authors.initials: K
authors.lastname: Norrgren
authors.forename: R
authors.initials: R
authors.lastname: Nilsson
authors.forename: H O
authors.initials: HO
authors.lastname: Sjögren
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D001710:Biotin; D005260:Female; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D008175:Lung Neoplasms / Q000532:radiotherapy*; D008297:Male; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy; D051381:Rats; D011923:Rats, Nude; D014407:Tumor Cells, Cultured
chemical_list: D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D001710:Biotin