| First Author | Song H | Year | 2008 |
| Journal | Cancer Res | Volume | 68 |
| Issue | 10 | Pages | 3873-80 |
| PubMed ID | 18483272 | Mgi Jnum | J:135020 |
| Mgi Id | MGI:3790261 | Doi | 10.1158/0008-5472.CAN-07-6308 |
| Citation | Song H, et al. (2008) 213Bi (alpha-emitter)-antibody targeting of breast cancer metastases in the neu-N transgenic mouse model. Cancer Res 68(10):3873-80 |
| abstractText | 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 alpha-particle emitter (213)Bi 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 muCi of (213)Bi-7.16.4. The kinetics of marrow suppression and subsequent recovery were determined. Three days after left cardiac ventricular injection of 10(5) rat HER-2/neu--expressing syngeneic tumor cells, neu-N mice were treated with (a) 120 muCi (213)Bi-7.16.4, (b) 90 muCi (213)Bi-7.16.4, (c) 120 muCi (213)Bi-Rituximab (unreactive control), and (d) unlabeled 7.16.4. Treatment with 120 muCi (213)Bi-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 alpha-emitter (213)Bi-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. |
