Alpha-v Integrin Targeted PET Imaging of Breast Cancer Angiogenesis and Low-Dose Metronomic Anti-Angiogenic Chemotherapy Efficacy
Addendum to final rept. 15 Jul 2007-14 Jul 2008
STANFORD UNIV CA SCHOOL OF MEDICINE
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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 PET18F-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 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 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.
- Medicine and Medical Research