title: Peptide-conjugated polymeric micellar nanoparticles for Dual SPECT and optical imaging of EphB4 receptors in prostate cancer xenografts.
abstract: EphB4, a member of the largest family of receptor tyrosine kinases, is overexpressed in numerous tumors. In this study, we developed a new class of multimodal nanoplatform for dual single photon emission computed tomography (SPECT) and near-infrared fluorescence imaging of EphB4. EphB4-binding peptide TNYL-FSPNGPIARAW (TNYL-RAW) was conjugated to polyethylene glycol-coated, core-crosslinked polymeric micelles (CCPM) dually labeled with near-infrared fluorescence fluorophores (Cy7) and a radioisotope (indium 111). In vitro, TNYL-RAW-CCPM selectively bound to EphB4-positive PC-3M prostate cancer cells, but not to EphB4-negative A549 lung cancer cells. In vivo, PC-3M tumors were clearly visualized by both SPECT and near-infrared fluorescence tomography after intravenous administration of (111)In-labeled TNYL-RAW-CCPM. In contrast, there was little signal in A549 tumors of mice injected with (111)In-labeled TNYL-RAW-CCPM or in PC-3M tumors of mice injected with (111)In-labeled CCPM. The high accumulation of (111)In-labeled TNYL-RAW-CCPM in PC-3M tumor could be significantly reduced after co-injection with an excess amount of TNYL-RAW peptide. Immunohistochemical analysis showed that fluorescence signal from the nanoparticles correlated with their radioactivity count, and co-localized with the EphB4 expressing region. (111)In-labeled TNYL-RAW-CCPM allowed visualization of cancer cells overexpressing EphB4 by both nuclear and optical techniques. The complementary information acquired with multiple imaging techniques should be advantageous in early detection of cancer.
authors: Department of Experimental Diagnostic Imaging, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. zhangruiyantai@hotmail.com
authors: Rui
authors: R
authors: Zhang
authors: Chiyi
authors: C
authors: Xiong
authors: Miao
authors: M
authors: Huang
authors: Min
authors: M
authors: Zhou
authors: Qian
authors: Q
authors: Huang
authors: Xiaoxia
authors: X
authors: Wen
authors: Dong
authors: D
authors: Liang
authors: Chun
authors: C
authors: Li
references: Am J Pathol. 2003 Apr;162(4):1037-42
references: 12651595
references: Blood. 2007 Jun 15;109(12):5355-62
references: 17317854
references: Proc Natl Acad Sci U S A. 2010 Apr 27;107(17):7910-5
references: 20385821
references: J Nucl Med. 2008 Jun;49 Suppl 2:113S-28S
references: 18523069
references: Nat Rev Mol Cell Biol. 2005 Jun;6(6):462-75
references: 15928710
references: Mol Cancer Ther. 2007 Mar;6(3):844-55
references: 17339368
references: Oncogene. 2006 Feb 2;25(5):769-80
references: 16205642
references: Biomaterials. 2010 Apr;31(10):2866-73
references: 20053440
references: Biomaterials. 2008 Jun;29(16):2548-55
references: 18329706
references: Proc Natl Acad Sci U S A. 2004 Apr 13;101(15):5583-8
references: 15067119
references: Am J Pathol. 2006 Jul;169(1):279-93
references: 16816380
references: Oncogene. 2000 Nov 20;19(49):5614-9
references: 11114742
references: EMBO J. 2006 Feb 8;25(3):628-41
references: 16424904
references: J Pept Sci. 2007 Sep;13(9):581-7
references: 17631671
references: J Am Chem Soc. 2010 Aug 18;132(32):11306-13
references: 20698697
references: J Nucl Med. 2009 Nov;50(11):1743-6
references: 19837751
references: Bioessays. 2008 Sep;30(9):904-18
references: 18693269
references: J Cell Sci. 2004 Apr 15;117(Pt 10):2037-49
references: 15054110
references: J Neurosci. 2004 Nov 10;24(45):10064-73
references: 15537875
references: Nat Neurosci. 2003 Apr;6(4):339-40
references: 12640461
references: Nano Lett. 2006 Apr;6(4):669-76
references: 16608262
references: J Am Chem Soc. 2010 Nov 3;132(43):15351-8
references: 20942456
references: Biomaterials. 2010 Apr;31(11):3023-31
references: 20106519
references: Biomaterials. 2010 Apr;31(11):3016-22
references: 20092887
references: J Biol Chem. 2005 Apr 29;280(17):17301-11
references: 15722342
references: Microsc Res Tech. 2002 Oct 1;59(1):58-67
references: 12242697
references: Curr Pharm Des. 2009;15(6):585-6
references: 19199983
references: Eur J Nucl Med Mol Imaging. 2008 Dec;35(12):2235-44
references: 18566815
references: Biomacromolecules. 2007 Nov;8(11):3422-8
references: 17958440
references: Bioconjug Chem. 2009 Feb;20(2):397-401
references: 19138113
references: Cancer Res. 2009 May 1;69(9):3736-45
references: 19366806
references: Biomaterials. 2010 Nov;31(33):8724-31
references: 20728213
references: J Nucl Med. 2011 Feb;52(2):241-8
references: 21233177