Near-infrared optical imaging in glioblastoma xenograft with ligand-targeting alpha 3 integrin.

European Journal of Nuclear Medicine and Molecular Imaging
Wenwu XiaoKit S Lam

Abstract

Patients with glioblastoma usually have a very poor prognosis. Even with a combination of radiotherapy plus temozolomide, the median survival of these patients is only 14.6 months. New treatment approaches to this cancer are needed. Our purpose is to develop new cell surface-binding ligands for glioblastoma cells and use them as targeted imaging and therapeutic agents for this deadly disease. One-bead one-compound combinatorial cyclic peptide libraries were screened with live human glioblastoma U-87MG cells. The binding affinity and targeting specificity of peptides identified were tested with in vitro experiments on cells and in vivo and ex vivo experiments on U-87MG xenograft mouse model. A cyclic peptide, LXY1, was identified and shown to be binding to the alpha 3 integrin of U-87MG cells with moderately high affinity (K (d) = 0.5 +/- 0.1 microM) and high specificity. Biotinylated LXY1, when complexed with streptavidin-Cy5.5 (SA-Cy5.5) conjugate, targeted both subcutaneous and orthotopic U-87MG xenograft implants in nude mice. The in vivo targeting specificity was further verified by strong inhibition of tumor uptake of LXY1-biotin-SA-Cy5.5 complex when intravenously injecting the animals with anti-alpha 3 integrin antibody ...Continue Reading

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Citations

Dec 17, 2008·Pharmaceutical Research·Esmaiel Jabbari
Mar 17, 2010·Chemical Reviews·Seulki LeeXiaoyuan Chen
May 7, 2011·Theranostics·Yunpeng Ye, Xiaoyuan Chen
Apr 9, 2010·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Fei LiuYueqing Gu
May 4, 2012·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Didel M MahoungaYueqing Gu
Nov 25, 2014·Applied Biochemistry and Biotechnology·Chunlong SunMin Ji
Nov 5, 2016·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Lina Y HuJulie L Sutcliffe
May 24, 2016·Advanced Drug Delivery Reviews·Ruiwu LiuKit S Lam
Nov 29, 2011·International Journal of Cancer. Journal International Du Cancer·Rana FilfilAnne E G Lenferink
May 13, 2014·Journal of Veterinary Internal Medicine·P J Dickinson
Jun 19, 2018·Advanced Biosystems·Randy P CarneyKit S Lam
Jun 12, 2019·Journal of Hematology & Oncology·Wenwu XiaoTianhong Li
Jun 6, 2009·Accounts of Chemical Research·Margret SchotteliusHans-Jürgen Wester
Oct 20, 2009·Journal of Medicinal Chemistry·Nianhuan YaoKit S Lam
Dec 5, 2013·Chemical Reviews·Bethany Powell Gray, Kathlynn C Brown

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