Our long-range objectives are to develop PET imaging techniques for brain tumor imaging in order to identify molecular structures and receptors that are altered during brain tumor growth and spread and to help predict the natural history and response to therapy. The objective in this proposal is to image brain tumor angiogenesis and anti-angiogenic therapy efficacy by means of PET and MRI. Brain tumors are angiogenesis dependent. Anti-angiogenic therapies that either block expression of tumor angiogenesis related proteins or directly prevent endothelial cells from migration and induce apoptosis, have been proven effective in brain tumors. We have previously developed a series of cyclic RGB peptide radiotracers for PET imaging of brain tumor models based upon av-integrin antagonism. The tumor targeting efficacy and pharmacokinetics of the tracers are highly dependent on their receptor binding affinity, hydrophilicity, and molecular size, etc. This project will expand our investigations with aim to: (1) optimize the integrin specific PET tracers for clinical applicability; (2) correlate alpha-v integrin expression level with the magnitude of tumor (both tumor cells and rumor vasculature) tracer uptake; and (3) evaluate anti-integrin brain tumor treatment with a PET/MRI combination. Overall, this proposal will foster in a novel and unique way our understanding of brain tumor angiogenesis in relationship to alpha-v integrin expression and allow for direct assessment of anti-angiogenic treatment efficacy based upon alpha-integrin targeted PET imaging. This should lead to direct clinical translation of the PET probes validated and also allow imaging of angiogensis for other tumors (e.g., for lymphomas studied in Research Project 2). Furthermore it should help show the role of imaging to monitor anti-cancer therapies for acceleration of testing of new generation of anti-angiogenesis agents.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA114747-03
Application #
7478526
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
3
Fiscal Year
2007
Total Cost
$225,401
Indirect Cost
Name
Stanford University
Department
Type
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Natarajan, Arutselvan; Patel, Chirag B; Ramakrishnan, Sindhuja et al. (2018) A Novel Engineered Small Protein for Positron Emission Tomography Imaging of Human Programmed Death Ligand-1 : Validation in Mouse Models and Human Cancer Tissues. Clin Cancer Res :
Sun, Yao; Zeng, Xiaodong; Xiao, Yuling et al. (2018) Novel dual-function near-infrared II fluorescence and PET probe for tumor delineation and image-guided surgery. Chem Sci 9:2092-2097
Natarajan, Arutselvan; Patel, Chirag B; Habte, Frezghi et al. (2018) Dosimetry Prediction for Clinical Translation of 64Cu-Pembrolizumab ImmunoPET Targeting Human PD-1 Expression. Sci Rep 8:633
Habte, Frezghi; Natarajan, Arutselvan; Paik, David S et al. (2018) Quantification of Cerenkov Luminescence Imaging (CLI) Comparable With 3-D PET Standard Measurements. Mol Imaging 17:1536012118788637
Hong, Su Hyun; Sun, Yao; Tang, Chu et al. (2017) Chelator-Free and Biocompatible Melanin Nanoplatform with Facile-Loading Gadolinium and Copper-64 for Bioimaging. Bioconjug Chem 28:1925-1930
Shen, Bin; Behera, Deepak; James, Michelle L et al. (2017) Visualizing Nerve Injury in a Neuropathic Pain Model with [18F]FTC-146 PET/MRI. Theranostics 7:2794-2805
Loft, Mathias Dyrberg; Sun, Yao; Liu, Changhao et al. (2017) Improved positron emission tomography imaging of glioblastoma cancer using novel 68Ga-labeled peptides targeting the urokinase-type plasminogen activator receptor (uPAR). Amino Acids 49:1089-1100
Natarajan, Arutselvan; Mayer, Aaron T; Reeves, Robert E et al. (2017) Development of Novel ImmunoPET Tracers to Image Human PD-1 Checkpoint Expression on Tumor-Infiltrating Lymphocytes in a Humanized Mouse Model. Mol Imaging Biol 19:903-914
Hori, Sharon Seiko; Lutz, Amelie M; Paulmurugan, Ramasamy et al. (2017) A Model-Based Personalized Cancer Screening Strategy for Detecting Early-Stage Tumors Using Blood-Borne Biomarkers. Cancer Res 77:2570-2584
Ronald, John A; Kim, Byung-Su; Gowrishankar, Gayatri et al. (2017) A PET Imaging Strategy to Visualize Activated T Cells in Acute Graft-versus-Host Disease Elicited by Allogenic Hematopoietic Cell Transplant. Cancer Res 77:2893-2902

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