Alpha-v Integrin Targeted PET Imaging of Breast Cancer Angiogenesis and Low-Dose Metronomic Anti-Angiogenic Chemotherapy Efficacy
Abstract
The overall objective of this project is to develop 18F-labeled RGD peptide derivatives for breast cancer imaging with prolonged tumor retention and improved in vivo kinetics to visualize and quantify v-integrin expression and subsequently evaluate the metronomic antiangiogenic 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 PET/18F-RGD to image breast tumor growth, spread, and angiogenesis as well as quantifying v-integrin expression level during breast tumor neovascularization over time. (3) To evaluate the efficacy of EMD 121974/paclitaxel combination on tumor regression, necrosis, and angiogenesis and demonstrate the feasibility of PET/18F-RGD to monitor the treatment outcomes. Major findings: We have developed a series of novel multimeric RGD peptides for PET imaging. We have also successfully demonstrated that suitably labeled RGD peptide allows quantification of integrin expression in vivo in a non-invasive manner. We have also synthesized a RGD-paclitaxel conjugate for breast cancer integrin targeted therapy. Furthermore, RGD peptide-based PET tracer allows early prediction of response to anti-cancer therapeutics including paclitaxtel derivatives.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2008
- Accession Number
- ADA588970
Entities
People
- Xiaoyuan Chen
Organizations
- Stanford University