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|Title:||Immunoliposomal Delivery of 213Bi for Alpha-emitter Targeting of Metastatic Breast Cancer|
|Authors:||LINGAPPA M.; SONG H.; THOMPSON S.; BRUCHERTSEIFER Frank; MORGENSTERN Alfred; SGOUROS G.|
|Citation:||CANCER RESEARCH vol. 70 no. 17 p. 6815-6823|
|Publisher:||AMER ASSOC CANCER RESEARCH|
|Type:||Articles in periodicals and books|
|Abstract:||Currently available treatment for late stage metastatic breast cancer is largely palliative. Alpha-particles are highly potent, short-range radiation emissions capable of sterilizing individual cells with one to three traversals of the cell nucleus. The alpha-emitter, 213Bi (T ½ = 45.6 min), was conjugated to a 100 nm-diameter liposomal-CHX-A¿-DTPA construct, upon which the rat HER2/neu reactive antibody, 7.16.4 had been previously grafted. A conjugation time of approximately 10 min was achieved giving a specific activity corresponding to 0.1 213Bi atom per liposome; stablility in-vitro and in-vivo was confirmed. The efficacy of this construct in a rat/neu transgenic mouse model of metastatic mammary carcinoma was investigated. Three days after left cardiac ventricular injection of 105 rat HER-2/neu expressing syngeneic tumor cells, macrophage depleted Neu-N mice were treated, by IV injection, with: (a) 20.4 MBq (550 µCi) liposome-CHX-A¿-DTPA-213Bi, (b) 20.4 MBq of liposome-CHX-A¿-DTPA-213Bi-7.16.4 and (c) cold (non-radioactive) liposome-CHX-A¿-DTPA-7.16.4 as control. Treatment with (a) increased median survival time to 36 days compared with 29.5 days for the untreated controls (P < 17 0.0001) and 27 days for treated cold controls. Treatment with the antibody conjugated liposome (b) increased median survival time to 44 days (p < 0.0001 relative to untreated controls). Immunoliposomal delivery of 213Bi offers the possibility of substantially increasing the number of alpha-particles delivered per targeted cell. We have shown that the 213Bi radiolabeled immunoliposomes are effective in treating early stage micrometastases, giving median survival times greater than those previously reported with antibody-mediated delivery of 213Bi in this animal model.|
|JRC Institute:||Institute for Transuranium Elements|
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