Journal
BRITISH JOURNAL OF CANCER
Volume 88, Issue 6, Pages 944-950Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.bjc.6600838
Keywords
breast cancer; MDA-MB-231 cell line; targeted alpha therapy; alpha-particle emitter Bi-213; plasminogen activation inhibitor type 2
Categories
Ask authors/readers for more resources
The control of micrometastatic breast cancer remains problematic. To this end, we are developing a new adjuvant therapy based on Bi-213-PAI2, in which an alpha-emitting nuclide (Bi-213) is chelated to the plasminogen activator inhibitor-2 (PAI2). PAI2 targets the cell-surface receptor bound urokinase plasminogen activator (uPA), which is involved with the metastatic spread of cancer cells. We have successfully labelled and tested recombinant human PAI2 with the alpha radioisotope Bi-213 to produce Bi-213-PAI2, which is highly cytotoxic towards breast cancer cell lines. In this study, the 2-day postinoculation model, using MDA-MB-231 breast cancer cells, was shown to be representative of micrometastatic disease. Our in vivo efficacy experiments show that a single local injection of Bi-213-PAI2 can completely inhibit the growth of tumour at 2 days postcell inoculation, and a single systemic (i.p.) administration at 2 days causes tumour growth inhibition in a dose-dependent manner. The specific role of uPA as the target for Bi-213-PAI2 therapy was determined by PAI2 pretreatment blocking studies. In vivo toxicity studies in nude mice indicate that up to 100 muCi of Bi-213-PAI2 is well tolerated. Thus, Bi-213-PAI2 is successful in targeting isolated breast cancer cells and preangiogenic cell clusters. These results indicate the promising potential of Bi-213-PAI2 as a novel therapeutic agent for micrometastatic breast cancer. (C) 2003 Cancer Research UK.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available