Article
Radioimmunotherapy of SCCHN in xenotransplantated SCID-Mice with a I-131-labeled Anti-EpCAM monoclonal antibody
Untersuchungen zur Radioimmuntherapie und Radioimmunszintigraphie bei Kopf-Hals-Tumoren mit einem radioaktiv-markierten Antikörper gegen EpCAM im SCID-Mausmodell
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Published: | September 7, 2006 |
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Background: The mortality of squamous cell carcinoma of the head and neck (SCCHN) still remains worse. Therefore new therapeutical strategies are necessary. One promising approach is the application of radio-labeled antibodies against tumour-associated antigens. EpCAM, showing a de novo-expression on SCCHN, is a suitable anchor molecule for such a Radioimmunotherapy (RIT). Aim of this study was to establish an in vivo-model with a radio-labelled monoclonal antibody (MAb) against this antigen.
Materials and Methods: The MAb C215 was labeled with 131I and tested for its capacity to eradicate established SCCHN xenografts growing subcutaneous in SCID mice. Initially, the biodistribution was determined by scarifying mice and dissecting organs at a given time after administration of the radio-labeled antibody and measuring the % injected dose/gram tissue in the gammacounter. For therapy, mice received a single bolus injection of 5, 15 or 25 MBq 131I-labeled MAb C215. Control animals received sodium chloride or the unlabeled MAb. Tumor growth and weight of the animals were determined at a particular time after administration of the antibody.
Results: Tumors in the groups receiving sodium chloride, unlabeled MAb C215 or 5 MBq of 131I-labeled MAb C215 showed exponential growth. Tumors in the groups receiving 15 MBq or 25 MBq of 131I-labeled MAb C215 showed delay of growth or regression. Since treatment related toxicity continued reaching median of 20 % weight loss mice were sacrificed at day 17 (25 MBq) and day 23 (15 MBq). At that time treatment control ratio of 12 % (15 MBq) and 29 % (25 MBq) could be determined.
Conclusion: Our data demonstrate that using radio-labeled MAb C215 seems to be a promising tool to improve the outcome of SCCHN. Further studies are necessary to reduce the toxicity of such a therapy.