Orthotopic xenografts of human melanoma and colonic and ovarian carcinoma in sheep to evaluate radioimmunotherapy

Abstract

(CEA). The anti-CEA IgGl monoclonal antibody A5B7 was radiolabelled with iodine-131 and administered intravenously to sheep. Peak uptake at 5 days in orthotopic human tumour transplants in gut was 0.027% Dl g-' (percentage of injected dose per gram) and 0.034% Dl g-1 in hepatic metastases with tumour to blood ratios of 2-2.5. Non-specific tumour uptake in melanoma was 0.003% Dl g-1. Uptake of radiolabelled monoclonal antibody in human tumours in our large animal model is comparable with that observed in patients and may be more realistic than nude mice xenografts for prediction of clinical efficacy of radioimmunotherapy.

The New Golden Era for Radioimmunotherapy: Not Just for Lymphomas Anymore

“…Several other potential targets for RIT in OC have been described, but with little or no clinical experience. [123][124][125][126][127][128][129][130][131] RIT for OC appears to be a potentially promising option, particularly in patients who have been optimally debulked following surgery and chemotherapy but who still are at high risk for microscopic intraperitoneal disease. Alpha-emitting radionuclides hold particular promise in nonbulky disease, given the higher linear energy transfer and shorter path length compared with beta particles.…”

Intraperitoneal Radionuclide Therapy – Clinical and Pre-Clinical Considerations

“…NR-LU-10 has been used in clinical studies (Breitz et al, 1995;Jacobs et al, 1993). A5B7 is an anti-CEA IgG1 mAb that has been used in one large-animal model (sheep) study (Turner et al, 1998). 17-1A is a chimeric mAb is directed towards a ~39 kDa membrane-associated pancarcinoma glycoprotein (Edwards et al, 1986;Koprowski et al, 1979).…”

“…131 I-A5B7 In a large animal study of human tumors in cyclosporin-immunosuppressed sheep, by Turner et al, evaluation and measurement of tumor uptake of 131 I-mAbs was done (Turner et al, 1998). Human cancer cells were orthotopically inoculated (~10 7 cells): SKMEL melanoma subcutaneously; LS174T and HT29 colon carcinoma into bowel, peritoneum and liver; and JAM ovarian carcinoma into the ovary and peritoneum.…”

“…It emits -radiation (364 keV) enabling scintigraphy and dosimetry. 131 I has been used in animal studies (Kievit et al, 1996;Turner et al, 1998) and in clinical studies (Buchsbaum et al, 1999;Buijs et al, 1998;Buist et al, 1993;Colcher et al, 1987;Crippa et al, 1995;Epenetos et al, 1987;Mahé et al, 1999;Molthoff et al, , 1997Muto et al, 1992;Stewart et al, 1989aStewart et al, , 1989bVan Zanten-Przybysz et al, 2000. 186 and 188 .…”

Neoplasms of the Reproductive Tract: The Role of Hormone Exposure

“…Ovarian epithelial neoplasms have been reported in several domestic species and most often in the dog, in which they appear to be the most common ovarian neoplasm and tend to be malignant (Patnaik and Greenlee 1987). In a particularly unusual study, human ovarian neoplasms were orthotopically transplanted into cyclosporin-immunosuppressed sheep for studies of radiotherapy because smaller animal models did not provide adequate modeling of tissue mass for dosimetry (Turner et al 1998). Cervical neoplasms in domestic species are rare.…”