title: In vivo diagnosis of murine pancreatic intraepithelial neoplasia and early-stage pancreatic cancer by molecular imaging.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is a fatal disease with poor patient outcome often resulting from late diagnosis in advanced stages. To date methods to diagnose early-stage PDAC are limited and in vivo detection of pancreatic intraepithelial neoplasia (PanIN), a preinvasive precursor of PDAC, is impossible. Using a cathepsin-activatable near-infrared probe in combination with flexible confocal fluorescence lasermicroscopy (CFL) in a genetically defined mouse model of PDAC we were able to detect and grade murine PanIN lesions in real time in vivo. Our diagnostic approach is highly sensitive and specific and proved superior to clinically established fluorescein-enhanced imaging. Translation of this endoscopic technique into the clinic should tremendously improve detection of pancreatic neoplasia, thus reforming management of patients at risk for PDAC.
authors.affiliation: II Medizinische Klinik, Technische Universität München, 81675 Munich, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Eser
authors.forename: Marlena
authors.initials: M
authors.lastname: Messer
authors.forename: Philipp
authors.initials: P
authors.lastname: Eser
authors.forename: Alexander
authors.initials: A
authors.lastname: von Werder
authors.forename: Barbara
authors.initials: B
authors.lastname: Seidler
authors.forename: Monther
authors.initials: M
authors.lastname: Bajbouj
authors.forename: Roger
authors.initials: R
authors.lastname: Vogelmann
authors.forename: Alexander
authors.initials: A
authors.lastname: Meining
authors.forename: Johannes
authors.initials: J
authors.lastname: von Burstin
authors.forename: Hana
authors.initials: H
authors.lastname: Algül
authors.forename: Philipp
authors.initials: P
authors.lastname: Pagel
authors.forename: Angelika E
authors.initials: AE
authors.lastname: Schnieke
authors.forename: Irene
authors.initials: I
authors.lastname: Esposito
authors.forename: Roland M
authors.initials: RM
authors.lastname: Schmid
authors.forename: Günter
authors.initials: G
authors.lastname: Schneider
authors.forename: Dieter
authors.initials: D
authors.lastname: Saur
mesh_terms: D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D002403:Cathepsins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005456:Fluorescent Dyes / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D057054:Molecular Imaging / Q000379:methods*; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D005456:Fluorescent Dyes; D002403:Cathepsins