title: Measuring response to therapy by near-infrared imaging of tumors using a phosphatidylserine-targeting antibody fragment.
abstract: Imaging tumors and their response to treatment could be a valuable biomarker toward early assessment of therapy in patients with cancer. Phosphatidylserine (PS) is confined to the inner leaflet of the plasma membrane in normal cells but is externalized on tumor vascular endothelial cells (ECs) and tumor cells, and PS exposure is further enhanced in response to radiation and chemotherapy. In the present study, we evaluated the potential of a PS-targeting human F(ab')2 antibody fragment, PGN650, to detect exposure of PS in tumor-bearing mice. Tumor uptake of PGN650 was measured by near-infrared optical imaging in human tumor xenografts in immunodeficient mice. PGN650 specifically targeted tumors and was shown to target CD31-positive ECs and tumor cells. Tumor uptake of PGN650 was significantly higher in animals pretreated with docetaxel. The peak tumor to normal tissue (T/N) ratio of probe was observed at 24 hours postinjection of probe, and tumor binding was detected for at least 120 hours. In repeat dose studies, PGN650 uptake in tumors was significantly higher following pretreatment with docetaxel compared to baseline uptake prior to treatment. PGN650 may be a useful probe to detect PS exposed in tumors and to monitor enhanced PS exposure to optimize therapeutic agents to treat tumors.
authors: Jian
authors: J
authors: Gong
authors: Richard
authors: R
authors: Archer
authors: Michael
authors: M
authors: Brown
authors: Seth
authors: S
authors: Fisher
authors: Connie
authors: C
authors: Chang
authors: Matthew
authors: M
authors: Peacock
authors: Christopher
authors: C
authors: Hughes
authors: Bruce
authors: B
authors: Freimark
mesh_terms: D000906:Antibodies / Q000737:chemistry*; D003952:Diagnostic Imaging / Q000379:methods*; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D009369:Neoplasms; D010718:Phosphatidylserines / Q000737:chemistry*
chemical_list: D000906:Antibodies; D010718:Phosphatidylserines
references: Eur J Nucl Med Mol Imaging. 2007 Jun;34(6):889-99
references: 17216472
references: Clin Cancer Res. 2007 Sep 1;13(17):5211-8
references: 17785577
references: Mol Imaging. 2004 Jan;3(1):1-8
references: 15142407
references: Annu Rev Physiol. 2003;65:701-34
references: 12471163
references: Cancer Res. 2005 May 15;65(10):4408-16
references: 15899833
references: Pathophysiol Haemost Thromb. 2008;36(3-4):177-83
references: 19176990
references: J Nucl Med. 2004 Jan;45(1):108-15
references: 14734682
references: Clin Cancer Res. 2002 Sep;8(9):2766-74
references: 12231515
references: Cancer Res. 2002 Nov 1;62(21):6132-40
references: 12414638
references: Clin Cancer Res. 2009 Nov 15;15(22):6871-80
references: 19887482
references: EJNMMI Res. 2012 Apr 01;2:14
references: 22464315
references: Biochim Biophys Acta. 2006 Aug;1761(8):913-26
references: 16624617
references: J Thromb Haemost. 2007 Dec;5(12):2445-52
references: 17922809
references: Eur J Nucl Med Mol Imaging. 2004 Jun;31(6):887-919
references: 15138718
references: Mol Membr Biol. 1994 Oct-Dec;11(4):199-216
references: 7711830
references: Int J Cancer. 2006 May 15;118(10):2639-43
references: 16353142
references: Ann N Y Acad Sci. 2003 Dec;1010:525-9
references: 15033784
references: Bioorg Med Chem. 2005 Sep 1;13(17):5035-42
references: 15914007
references: Int J Radiat Oncol Biol Phys. 2002 Dec 1;54(5):1479-84
references: 12459374
references: Methods Mol Med. 2005;111:363-80
references: 15911991
references: Circulation. 1995 Nov 15;92(10):3113-21
references: 7586283
references: Eur J Nucl Med Mol Imaging. 2007 Feb;34(2):247-58
references: 17021816
references: Nat Med. 2001 Dec;7(12):1347-52
references: 11726976
references: Nat Med. 1995 Feb;1(2):149-53
references: 7585012
references: Neoplasia. 2011 Apr;13(4):299-308
references: 21472134
references: J Biol Chem. 1995 Dec 8;270(49):29075-8
references: 7493929
references: J Nucl Med. 2003 Jun;44(6):947-52
references: 12791824
references: Am J Transplant. 2001 Sep;1(3):270-7
references: 12102261
references: Clin Cancer Res. 2008 Mar 1;14(5):1377-85
references: 18316558
references: Transl Oncol. 2011 Dec;4(6):355-64
references: 22191000
references: J Lipid Res. 2003 Feb;44(2):233-42
references: 12576505
references: Eur J Nucl Med Mol Imaging. 2006 May;33(5):566-74
references: 16477433
references: J Nucl Med. 1999 Jan;40(1):184-91
references: 9935075
references: Br J Pharmacol. 2004 Sep;143(1):99-106
references: 15289297
references: In Vitro Cell Dev Biol. 1987 May;23(5):387-94
references: 2438264
references: J Biol Chem. 2006 Oct 6;281(40):29863-71
references: 16905548
references: Clin Cancer Res. 2005 Feb 15;11(4):1551-62
references: 15746060
references: Biochemistry. 1986 May 6;25(9):2585-90
references: 3013308
references: Clin Cancer Res. 2011 Nov 1;17(21):6888-96
references: 21989064
references: Clin Cancer Res. 2002 Sep;8(9):2757-8
references: 12231512
references: Mol Pharm. 2009 Nov-Dec;6(6):1903-19
references: 19743879
references: Clin Cancer Res. 2001 Jan;7(1):5-22
references: 11205917