[sup 90]Y-labeled antibody uptake by human tumor xenografts and the effect of systemic administration of EDTA

Journal Article · Wed Mar 30 04:00:00 EST 1994 · International Journal of Radiation Oncology, Biology and Physics; (United States)

DOI:https://doi.org/10.1016/0360-3016(94)90503-7· OSTI ID:6787073

Rowlinson-Busza, G; Snook, D; Epenetos, A A ^[1]

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1. Royal Postgraduate Medical School, London (United Kingdom)

A human tumor xenograft model was used to compare the tumor and normal tissue uptake of a tumor-associated monoclonal antibody radiolabeled with [sup 125]I or [sup 90]Y. Nude mice bearing SC xenografts of the human colon adenocarcinoma, HT29, were injected with a mixture of [sup 125]I- and [sup 90]Y-DTPA-labeled AUA1 monoclonal antibody, which recognizes an antigen expressed on the surface of the tumor cells. In addition, the effect of systemic ethylenediaminetetraacetic acid (EDTA) administration on [sup 90]Y-labeled antibody clearance, tumor uptake of antibody and bone accumulation of [sup 90]Y was studied in a nude mouse model of intraperitoneal cancer. Both the absolute amount (%id[center dot]g[sup -1]) and the tumor:normal tissue ratios were superior for the [sup 90]Y-labeled antibody, compared with the iodinated antibody, with the notable exception of bone. These results suggest that [sup 90]Y is a preferable isotope to iodine for radioimmunotherapy of solid masses, but that myelotoxicity due to bone uptake of released [sup 90]Y will limit the radiation dose which can be given when DTPA is used to chelate the [sup 90]Y. The [sup 90]Y-labeled antibody showed similar serum stability in vitro in the presence or absence of EDTA after incubation for up to 48 h. In vivo, urine excretion of [sup 90]Y was significantly enhanced in mice receiving daily injections of 20 mg EDTA for 3 days, commencing 2 h after intraperitoneal antibody administration, compared with control mice. There was no significant difference in the tumor uptake of [sup 90]Y-labeled antibody in EDTA-treated and control mice at any time-point up to 9 days postinjection. However, the bone levels of [sup 90]Y were significantly reduced in EDTA-treated mice at all times from 1 to 9 days. Based on these results, it should be possible to increase the amount of [sup 90]Y-labeled antibody administered, by chelating the released [sup 90]Y with systemic EDTA to facilitate its excretion. 50 refs., 5 figs.

• OSTI ID: 6787073
• Journal Information: International Journal of Radiation Oncology, Biology and Physics; (United States), Journal Name: International Journal of Radiation Oncology, Biology and Physics; (United States) Vol. 28:5; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

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