Intratumour injection of immunoglobulins labelled with the alpha-particle emitter 211At: analyses of tumour retention, microdistribution and growth delay
| Autor: | O. S. Bruland, R. H. Larsen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 1998 |
| Předmět: |
Cancer Research
Ratón Radioimmunoconjugate medicine.drug_class medicine.medical_treatment Immunoglobulins Mice Nude Injections Intralesional Monoclonal antibody Mice In vivo medicine Animals Humans Osteosarcoma biology Chemistry business.industry Radioimmunotherapy medicine.disease Molecular biology Oncology Polyclonal antibodies biology.protein Autoradiography Antibody Subrenal Capsule Assay Nuclear medicine business Astatine Research Article |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | To determine the effects of 211At-labelled antibodies in solid tumour tissue, nude mice carrying OHS human osteosarcoma xenografts received intratumour injections at dosages of 1, 2 or 4 MBq (-1) tumour. The radioisotope was conjugated to either the osteosarcoma-specific monoclonal antibody TP-3 or the non-specific polyclonal antibody hlgGkappa. Tumour retention of injected radioimmunoconjugate (RIC), measured as the percentage of injected activity dosage per gram, was significantly higher for the [211At]TP-3 (203 +/- 93 at 24.1 h post injection) compared with the [211At]hlgGkappa (57 +/- 22 at 23.2 h post injection). The radioactive count rates in body (measured at neck and abdomen) were significantly lower with the TP-3 than with the hlgGkappa. Microautoradiography of the tumour radionuclide distribution was different for the two RICs, i.e. the [211At]TP-3 was to a larger extent concentrated near the injection site, whereas the [211At]hlgGkappa was more evenly distributed all over the tumour. The tumour growth was significantly delayed as a function of the injected activity dosage but without significant difference between the specific and the non-specific RIC. According to this study, it is possible to deliver highly selective radiation doses to solid tumours using intratumour injection of alpha-particle-emitting RICs. Improved tumour retention caused by antigen binding indicates that reduced normal tissue exposure can be obtained with antigen-specific antibodies. The heterogeneous tumour dose distribution observed is, however, a major impediment to the use of alpha-particle emitters against solid tumours. Images Figure 2 Figure 3 |
| Databáze: | OpenAIRE |
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