Alpha-V Integrin Targeted PET Imagining of Breast Cancer Angiogenesis and Lose-Dose Metronomic Anti-Angiogenic Chemotherapy Efficacy
Annual rept. 15 Jul 2004-14 Jul 2005
LELAND STANFORD JUNIOR UNIV STANFORD CA
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The overall objective of this project is to develop I 18F-labeled RGD peptide derivatives for breast cancer imaging with prolonged tumor retention and improved in vivo kinetics to visualize and quantify av-integrin expression and subsequently evaluate the metronomic anti angiogenic chemotherapy efficacy on tumor regression, necrosis, and angiogenesis. Specific Aims 1 To optimize 18F-labeled RGD peptide tracer for breast cancer imaging with prolonged tumor retention and improved in vivo kinetics. 2 To demonstrate the feasibility of PET18F-RGD to image breast tumor growth, spread, and angiogenesis as well as quantifying av-integrin expression level during breast tumor neovascularization overtime. 3 To evaluate the efficacy of EMD 121974paclitaxel combination on tumor regression, necrosis, and angiogenesis and demonstrate the feasibility of PET18F-RGD to monitor the treatment outcomes. Major findings We have developed a dimeric RGD peptide tracer 18FFRGD2 that has high integrin av beta 3 binding affinity and favorable in vivo kinetics. Furthermore, the binding potential calculated from simplified tracer kinetic modeling such as Logan plot appears to be an excellent indicator of tumor integrin density. We have also evaluated the antitumor activity of paclitaxel PTX conjugated with a bicyclic peptide EcRGDyK2 RGD in a metastatic breast cancer cell line MDA-MB-435. Our results demonstrate the potential of tumor-targeted delivery of paclitaxel based on the specific recognition of cell adhesion molecule av beta 3 integrin to reduce toxicity and enhance selective killing of cancer cells.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research