title: A peptide probe for targeted brown adipose tissue imaging.
abstract: The presence of brown adipose tissue responsible for thermogenic energy dissipation has been revealed in adult humans and has high clinical importance. Owing to limitations of current methods for brown adipose tissue detection, analysing the abundance and localization of brown adipose tissue in the body has remained challenging. Here we screen a combinatorial peptide library in mice and characterize a peptide (with the sequence CPATAERPC) that selectively binds to the vascular endothelium of brown adipose tissue, but not of intraperitoneal white adipose tissue. We show that in addition to brown adipose tissue, this peptide probe also recognizes the vasculature of brown adipose tissue-like depots of subcutaneous white adipose tissue. Our results indicate that the CPATAERPC peptide localizes to brown adipose tissue even in the absence of sympathetic nervous system stimulation. Finally, we demonstrate that this probe can be used to identify brown adipose tissue depots in mice by whole-body near-infrared fluorescence imaging.
authors.affiliation: 1] Center for Molecular Imaging, The Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center at Houston, Houston, Texas 77030, USA [2].
authors.forename: Ali
authors.initials: A
authors.lastname: Azhdarinia
authors.forename: Alexes C
authors.initials: AC
authors.lastname: Daquinag
authors.forename: Chieh
authors.initials: C
authors.lastname: Tseng
authors.forename: Sukhen C
authors.initials: SC
authors.lastname: Ghosh
authors.forename: Pradip
authors.initials: P
authors.lastname: Ghosh
authors.forename: Felipe
authors.initials: F
authors.lastname: Amaya-Manzanares
authors.forename: Eva
authors.initials: E
authors.lastname: Sevick-Muraca
authors.forename: Mikhail G
authors.initials: MG
authors.lastname: Kolonin
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism / Q000648:ultrastructure*; D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism / Q000648:ultrastructure*; D008297:Male; D051379:Mice; D015335:Molecular Probes / Q000737:chemistry / Q000378:metabolism*; D061848:Optical Imaging / Q000379:methods*; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000378:metabolism / Q000648:ultrastructure; D051598:Whole Body Imaging / Q000379:methods*
chemical_list: D015335:Molecular Probes; D019151:Peptide Library; D010455:Peptides
references.citation: J Clin Invest. 1998 Jul 15;102(2):412-20
references.pmid: 9664083
references.citation: J Nucl Med. 2006 Jun;47(6):999-1006
references.pmid: 16741310
references.citation: Curr Opin Chem Biol. 2001 Jun;5(3):308-13
references.pmid: 11479123
references.citation: J Immunol Methods. 2010 Aug 31;360(1-2):167-72
references.pmid: 20600076
references.citation: J Med Chem. 2013 Jan 24;56(2):406-16
references.pmid: 23214723
references.citation: Mol Imaging. 2003 Jan;2(1):37-49
references.pmid: 12926236
references.citation: Physiol Rev. 2004 Jan;84(1):277-359
references.pmid: 14715917
references.citation: Nature. 2009 Aug 27;460(7259):1154-8
references.pmid: 19641492
references.citation: Tissue Eng Part C Methods. 2013 May;19(5):336-44
references.pmid: 23017116
references.citation: J Nucl Med. 2012 Sep;53(9):1427-37
references.pmid: 22872743
references.citation: Circulation. 2012 Jun 5;125(22):2782-91
references.pmid: 22665886
references.citation: Circ Res. 2008 Jan 4;102(1):77-85
references.pmid: 17967785
references.citation: Cell Metab. 2012 Sep 5;16(3):348-62
references.pmid: 22940198
references.citation: N Engl J Med. 2009 Apr 9;360(15):1509-17
references.pmid: 19357406
references.citation: Nat Protoc. 2010 May;5(5):912-20
references.pmid: 20431536
references.citation: Annu Rev Med. 2012;63:217-31
references.pmid: 22034868
references.citation: Proc Natl Acad Sci U S A. 2011 Nov 15;108(46):18637-42
references.pmid: 22049339
references.citation: Technol Cancer Res Treat. 2012 Feb;11(1):95-104
references.pmid: 22181335
references.citation: FASEB J. 2006 May;20(7):979-81
references.pmid: 16581960
references.citation: Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13055-60
references.pmid: 12242328
references.citation: Am J Physiol Endocrinol Metab. 2009 Nov;297(5):E977-86
references.pmid: 19458063
references.citation: AJR Am J Roentgenol. 2009 Aug;193(2):359-66
references.pmid: 19620432
references.citation: Cell. 2012 Jul 20;150(2):366-76
references.pmid: 22796012
references.citation: Cell Stem Cell. 2011 Jul 8;9(1):74-86
references.pmid: 21683670
references.citation: Cancer Res. 2012 Oct 15;72(20):5198-208
references.pmid: 23071132
references.citation: N Engl J Med. 2009 May 7;360(19):2021-3
references.pmid: 19420373
references.citation: Proc Natl Acad Sci U S A. 2004 Feb 17;101(7):2058-63
references.pmid: 14769942
references.citation: Adv Drug Deliv Rev. 2006 Dec 30;58(15):1622-54
references.pmid: 17123658
references.citation: N Engl J Med. 2009 Apr 9;360(15):1500-8
references.pmid: 19357405
references.citation: Nat Med. 2002 Feb;8(2):121-7
references.pmid: 11821895
references.citation: J Nucl Med. 2004 Jul;45(7):1189-93
references.pmid: 15235065
references.citation: Ann Med. 2011 Mar;43(2):104-15
references.pmid: 21254898
references.citation: Am J Physiol Endocrinol Metab. 2007 Aug;293(2):E444-52
references.pmid: 17473055
references.citation: Med Phys. 2010 Nov;37(11):5961-70
references.pmid: 21158309
references.citation: Sci Transl Med. 2011 Nov 9;3(108):108ra112
references.pmid: 22072637
references.citation: Nat Med. 2004 Jun;10(6):625-32
references.pmid: 15133506
references.citation: N Engl J Med. 2009 Apr 9;360(15):1518-25
references.pmid: 19357407
references.citation: Cancer Res. 2009 Jun 15;69(12):5259-66
references.pmid: 19491274