1. Biodistribution of a monoclonal antibody-methotrexate conjugate (791T/36-MTX) in patients with colorectal cancer.
- Author
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Ballantyne KC, Perkins AC, Pimm MV, Garnett MC, Clegg JA, Armitage NC, Baldwin RW, and Hardcastle JD
- Subjects
- Aged, Colonic Neoplasms diagnostic imaging, Humans, Iodine Radioisotopes, Metabolic Clearance Rate, Methotrexate pharmacokinetics, Middle Aged, Radionuclide Imaging, Rectal Neoplasms diagnostic imaging, Antibodies, Monoclonal administration & dosage, Colonic Neoplasms metabolism, Methotrexate administration & dosage, Rectal Neoplasms metabolism
- Abstract
The monoclonal antibody (MAb) 791T/36 which has previously been shown to localise in colorectal cancer has been conjugated to methotrexate (MTX) for potential use as a chemotherapeutic agent in malignant disease. To examine its biodistribution and tumour localisation, 16 patients with primary colorectal cancer were injected intravenously with 131I-labelled 791T/36-MTX conjugate and imaged using a gamma camera after 48-72 hr. Serial blood samples were taken to determine the levels of circulating conjugate and samples of tumour and normal colon were assayed for uptake of radioactivity. Whole body biodistribution, visualised by gamma scintigraphy, and blood clearance of both the antibody and drug moieties of 791T/36-MTX were similar to that previously found with unconjugated antibody. Assays of tissue radioactivity showed positive tumour uptake of drug-antibody conjugate (T:NT greater than 1.9:1) in 13/15 primary tumour specimens (median T:NT = 2.9:1). These studies indicate that 791T/36-MTX conjugates may have potential in the treatment of metastatic colorectal carcinoma.
- Published
- 1988
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