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 alpha-v 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 PET/18F-RGD to image breast tumor growth spread and angiogenesis as well as quantifying alpha-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 previously reported that 18F-FB-E[c(RGDyK)]2 (18F-FRGD2) allows quantitative PET imaging of integrin alpha-v beta-3 expression. However the potential clinical translation was hampered by the relatively low radiochemical yield. We thus developed a new tracer 8F-FB-mini-PEG-E[c(RGDyK)]2 (18F-FPRGD2) that has improved radiolabeling yield without compromising the tumor targeting efficiency and in vivo kinetics. We also showed that RGD-Pacitaxel treatment cause significant reduction in tumor growth in integrin positive MDA-MB-435 breast cancer model which is superior to the combination of RGD and paclitaxel.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2006
- Accession Number
- ADA469375
Entities
People
- Xiaoyuan Chen
Organizations
- Stanford University