Targeted Hsp70 fluorescence molecular endoscopy detects dysplasia in Barrett's esophagus.
Barrett esophagus
Esophageal adenocarcinoma
Fluorescence molecular endoscopy
Hsp70
Surveillance strategies
Journal
European journal of nuclear medicine and molecular imaging
ISSN: 1619-7089
Titre abrégé: Eur J Nucl Med Mol Imaging
Pays: Germany
ID NLM: 101140988
Informations de publication
Date de publication:
05 2022
05 2022
Historique:
received:
11
05
2021
accepted:
03
10
2021
pubmed:
10
12
2021
medline:
21
4
2022
entrez:
9
12
2021
Statut:
ppublish
Résumé
The incidence of esophageal adenocarcinoma (EAC) has been increasing for decades without significant improvements in treatment. Barrett's esophagus (BE) is best established risk factor for EAC, but current surveillance with random biopsies cannot predict progression to cancer in most BE patients due to the low sensitivity and specificity of high-definition white light endoscopy. Here, we evaluated the membrane-bound highly specific Hsp70-specific contrast agent Tumor-Penetrating Peptide (Hsp70-TPP) in guided fluorescence molecular endoscopy biopsy. Hsp70 was significantly overexpressed as determined by IHC in dysplasia and EAC compared with non-dysplastic BE in patient samples (n = 12) and in high-grade dysplastic lesions in a transgenic (L2-IL1b) mouse model of BE. In time-lapse microscopy, Hsp70-TPP was rapidly taken up and internalized by human BE dysplastic patient-derived organoids. Flexible fluorescence endoscopy of the BE mouse model allowed a specific detection of Hsp70-TPP-Cy5.5 that corresponded closely with the degree of dysplasia but not BE. Ex vivo application of Hsp70-TPP-Cy5.5 to freshly resected whole human EAC specimens revealed a high (> 4) tumor-to-background ratio and a specific detection of previously undetected tumor infiltrations. In summary, these findings suggest that Hsp70-targeted imaging using fluorescently labeled TPP peptide may improve tumor surveillance in BE patients.
Identifiants
pubmed: 34882260
doi: 10.1007/s00259-021-05582-y
pii: 10.1007/s00259-021-05582-y
pmc: PMC9016004
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2049-2063Subventions
Organisme : NIDDK NIH HHS
ID : P30 DK132710
Pays : United States
Organisme : Deutsche Forschungsgemeinschaft
ID : SFB 824 B5
Informations de copyright
© 2021. The Author(s).
Références
Dig Dis Sci. 2018 Aug;63(8):2013-2021
pubmed: 29948557
Immunol Invest. 2000 May;29(2):131-7
pubmed: 10854181
Cancer Res. 2014 Dec 1;74(23):6903-12
pubmed: 25300920
Dis Esophagus. 2015 May-Jun;28(4):394-403
pubmed: 24708360
PLoS One. 2008 Apr 02;3(4):e1925
pubmed: 18382692
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
ACS Nano. 2019 Feb 26;13(2):1354-1364
pubmed: 30624916
J Biomed Opt. 2013 Oct;18(10):101302
pubmed: 23797876
J Leukoc Biol. 2007 Jan;81(1):15-27
pubmed: 16931602
Gastric Cancer. 2019 May;22(3):546-557
pubmed: 30426295
Int J Cancer. 1998 Sep 11;77(6):942-8
pubmed: 9714069
Endoscopy. 2016 Feb;48(2):A1-A13
pubmed: 26426999
Oncotarget. 2017 Aug 1;8(50):87095-87106
pubmed: 29152066
Cancer Res. 2018 Nov 1;78(21):6268-6281
pubmed: 30228173
J Immunol. 2005 Sep 1;175(5):2900-12
pubmed: 16116176
Curr Gastroenterol Rep. 2012 Jun;14(3):216-25
pubmed: 22453701
Gastroenterology. 2013 Jul;145(1):56-58
pubmed: 23684943
Int J Cancer. 2018 May 1;142(9):1911-1925
pubmed: 29235112
Nat Med. 2012 Jan 15;18(2):315-21
pubmed: 22245781
Proc Natl Acad Sci U S A. 2011 Jan 11;108(2):733-8
pubmed: 21187371
Cancer Cell. 2012 Jan 17;21(1):36-51
pubmed: 22264787
Ann Surg Oncol. 2011 Nov;18(12):3506-13
pubmed: 21509632
Cells. 2020 May 20;9(5):
pubmed: 32443761
J Natl Cancer Inst. 2011 Jul 6;103(13):1049-57
pubmed: 21680910
Gastroenterology. 2018 Jan;154(2):406-420
pubmed: 29037468
Melanoma Res. 2003 Apr;13(2):147-52
pubmed: 12690297
Leukemia. 2006 Nov;20(11):2076-9
pubmed: 16990768
J Natl Cancer Inst. 2008 Aug 20;100(16):1184-7
pubmed: 18695138
Int J Nanomedicine. 2015 Sep 08;10:5687-700
pubmed: 26392771
Cell Cycle. 2012 Dec 1;11(23):4328-38
pubmed: 23095673
Eur J Surg Oncol. 2011 Feb;37(2):168-74
pubmed: 21095095
Ann N Y Acad Sci. 2007 Oct;1113:192-201
pubmed: 17978282
World J Clin Cases. 2019 Feb 6;7(3):260-269
pubmed: 30746368
Nat Commun. 2018 Jul 4;9(1):2605
pubmed: 29973582
Clin Cancer Res. 2017 Jun 1;23(11):2730-2741
pubmed: 28119364
Curr Opin Gastroenterol. 2019 Sep;35(5):395-400
pubmed: 31306160
PLoS One. 2014 Aug 28;9(8):e105344
pubmed: 25165986
Cell Stress Chaperones. 2000 Nov;5(5):438-42
pubmed: 11189449
Br J Cancer. 2013 Jul 23;109(2):370-8
pubmed: 23839491
PLoS One. 2012;7(7):e41420
pubmed: 22911792
Gastroenterology. 2000 Aug;119(2):333-8
pubmed: 10930368
Int J Cancer. 1995 Apr 10;61(2):272-9
pubmed: 7705958
Gastroenterology. 2019 Aug;157(2):492-506.e2
pubmed: 30998992
Clin Cancer Res. 2018 Mar 1;24(5):1048-1061
pubmed: 29208671
Gut. 2019 Jan;68(1):7-10
pubmed: 29247063
Sci Transl Med. 2013 May 8;5(184):184ra61
pubmed: 23658246
Head Neck Oncol. 2009 Aug 13;1:32
pubmed: 19678942
N Engl J Med. 2011 Oct 13;365(15):1375-83
pubmed: 21995385
Cancer Genomics Proteomics. 2011 Mar-Apr;8(2):49-63
pubmed: 21471515
Gastroenterology. 2018 Dec;155(6):1720-1728.e4
pubmed: 30165050
Stem Cells Int. 2016;2016:3710836
pubmed: 26697073
Cell Stress Chaperones. 2008 Spring;13(1):1-10
pubmed: 18347936