2008/01/01 by Zhuang Liu, Clarke, Robert; id_orcid 0000-0001-5407-3123, Bobisse S +16 · 1 citation
Biochemistry, Genetics and Molecular Biology · Engineering · Materials Science · Medicine · Physics and Astronomy · #Cancer Genomics and Diagnostics #Carbon Nanotubes in Composites #Genetic factors in colorectal cancer #Graphene and Nanomaterials Applications #PARP inhibition in cancer therapy #cond-mat.mtrl-sci
paper · pdf · doi:10.1158/0008-5472
published as Cancer Res. 68 (2008) 6652-6660
openalex publication_date 2008/01/01 · arxiv created 2008/08/14 · arxiv updated 2009/12/01 · openalex created_date 2022/07/28 · openalex updated_date 2026/08/04
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.