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• W1987223060 abstract "The control of micrometastatic breast cancer remains problematic. To this end, we are developing a new adjuvant therapy based on 213Bi-PAI2, in which an α-emitting nuclide (213Bi) 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 α radioisotope 213Bi to produce 213Bi-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 213Bi-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 213Bi-PAI2 therapy was determined by PAI2 pretreatment blocking studies. In vivo toxicity studies in nude mice indicate that up to 100 μCi of 213Bi-PAI2 is well tolerated. Thus, 213Bi-PAI2 is successful in targeting isolated breast cancer cells and preangiogenic cell clusters. These results indicate the promising potential of 213Bi-PAI2 as a novel therapeutic agent for micrometastatic breast cancer." @default.
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• W1987223060 date "2003-03-01" @default.
• W1987223060 modified "2023-10-18" @default.
• W1987223060 title "Preclinical studies of targeted α therapy for breast cancer using 213Bi-labelled-plasminogen activator inhibitor type 2" @default.
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• W1987223060 doi "https://doi.org/10.1038/sj.bjc.6600838" @default.
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