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Metastatic disease is a major problem for prostate cancer (CaP) therapy.Multi-targeted therapy may increase the likelihood of complete targeting of micro-metastatic disease.The objective in this project was to investigate targeting micrometastatic CaP using Bi-213-labeled multiple alpha-radioimmunoconjugates.In the present study, we established tissue microarrays (TMAs), labelled 213Bi with two monoclonal antibodies (MAbs), an inhibitor, plasminogen activator inhibitor type 2 (PAI2) to form alpha conjugates (ACs) and established CaP spheroid models to mimic micrometastatic cancer in vitro and NOD-SCID metatstatic CaP animal models in vivo including subcutaneous (s.c), intra-prostate and intra-tibial models by PC-3 cell line.We tested multiple ACs (test and control) in our in vitro and invivo models using different activities.Multiple targeted alpha therapy (MTAT) with a cocktail of test ACs regressed cancer spheroid growth in a dose-dependent and size-dependent manner, and could effectively target small CaP spheroids (< 100 μ min size).