Accession Number : ADA443020


Title :   Alpha-V Integrin Targeted PET Imagining of Breast Cancer Angiogenesis and Lose-Dose Metronomic Anti-Angiogenic Chemotherapy Efficacy


Descriptive Note : Annual rept. 15 Jul 2004-14 Jul 2005


Corporate Author : LELAND STANFORD JUNIOR UNIV STANFORD CA


Personal Author(s) : Chen, Xiaoyuan


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a443020.pdf


Report Date : Aug 2005


Pagination or Media Count : 94


Abstract : 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 PET/18F-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 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 dimeric RGD peptide tracer [18F]FRGD2 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 E[c(RGDyK)]2 (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.


Descriptors :   *BREAST CANCER , *ANGIOGENESIS , PEPTIDES , TOXICITY , ADHESION , NEOPLASMS , IN VIVO ANALYSIS , BLOOD VESSELS , CHEMOTHERAPY , NECROSIS , MAMMARY GLANDS , GROWTH(PHYSIOLOGY) , BIOMOLECULES , CHEMICAL DERIVATIVES


Subject Categories : Genetic Engineering and Molecular Biology
      Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE