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|Title:||213Bi (Alpha-emitter)-Antibody Targeting of Breast Cancer Metastases in the neu-N Transgenic Mouse Model|
|Authors:||SONG H.; SHAHVERDI K.; HUSO D. L.; ESAIAS C.; FOX J.; LIEDY A.; ZHANG Z.; REILLY R. T.; APOSTOLIDIS CHRISTOS; MORGENSTERN ALFRED; SGOUROS G.|
|Citation:||CANCER RESEARCH vol. 68 no. 10 p. 3873-3880|
|Publisher:||AMER ASSOC CANCER RESEARCH|
|Type:||Articles in periodicals and books|
|Abstract:||Treatment failure in breast cancer is largely the failure to control metastatic dissemination. In this study, we investigated the efficacy of an antibody against the rat variant of HER-2/neu, labeled with the -particle emitter 213Bi to treat widespread metastases in a rat/neu transgenic mouse model of metastatic mammary carcinoma. The model manifests wide-spread dissemination of tumor cells leading to osteolytic bone lesions and liver metastases, common sites of clinical metastases. The maximum tolerated dose was 120 µCi of 213Bi-7.16.4. The kinetics of marrow suppression and subsequent recovery were determined. Three days after left cardiac ventricular injection of 105 rat HER-2/neu--expressing syngeneic tumor cells, neu-N mice were treated with (a) 120 µCi 213Bi-7.16.4, (b) 90 µCi 213Bi-7.16.4, (c) 120 µCi 213Bi-Rituximab (unreactive control), and (d) unlabeled 7.16.4. Treatment with 120 µCi 213Bi-7.16.4 increased median survival time to 41 days compared with 28 days for the untreated controls (P < 0.0001); corresponding median survival times for groups b, c, and d were 36 (P < 0.001), 31 (P < 0.01), and 33 (P = 0.05) days, respectively. Median survival relative to controls was not significantly improved in mice injected with 10-fold less cells or with multiple courses of treatment. We concluded that -emitter 213Bi-labeled monoclonal antibody targeting the HER-2/neu antigen was effective in treating early-stage HER-2/neu--expressing micrometastases. Analysis of the results suggests that further gains in efficacy may require higher specific activity constructs or target antigens that are more highly expressed on tumor cells.|
|JRC Directorate:||Nuclear Safety and Security|
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