Treatment of Prostate Cancer by Targeting Vascular Endothelial Growth Factor Receptors (VEGFRs) and Micrometastases With Bismuth-213 Labeled Vectors
Abstract
The main purpose of the proposed study was to evaluate the toxicity and efficacy of multiple targeting vectors for the treatment of prostate cancer in mouse models. It included Avastin, an anti-vascular endothelial growth factor (VEGF) antibody and PAI2, a protein that targets uroplasminogen activation (uPA) receptors in the PA system; both to be used in combination therapy together with labeling with alpha-emitting radionuclide, Bismuth-213. New methods for the labeling of Avastin were developed with labeling efficiency in excess of 90%. The resulting conjugate was tested for in vitro stability and was found to be stable with less than 20% leaching over a period of 5 half-lives of the isotope. Enhancement of plasminogen activation expression was achieved with VEGF with PC3 cell line showing the maximum enhancement, DU145 showing some enhancement whereas LN3-LNCaP showing no change in its other negative uPA expression. VEGF secretion was estimated for the three cell lines and based on that PC3 was chosen for the tumour model development. Subcutaneous and orthotopic tumour models were successfully developed in mice and are subject of the ongoing in vivo studies. Successful labeling and stability testing of the Avastin conjugate is world first and remains the most significant finding of the study to-date.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2006
- Accession Number
- ADA471499
Entities
People
- Syed M. Abbas Rizvi
Organizations
- University of New South Wales