title: Multimodal molecular imaging of integrin αvβ3 for in vivo detection of pancreatic cancer.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease. Late detection of then nonresectable or metastasized tumors emphasizes the need for novel imaging approaches. Here, we report on so far nonexploited potentials of αvβ3 integrin-targeted molecular imaging technologies for detection of PDAC using genetically engineered mouse models.
  
  
  METHODS
  Immunohistochemistry and Western blot were used for characterization of αvβ3 expression in murine and human PDAC. We applied IntegriSense 680 fluorescence molecular tomography, intraoperative fluorescence imaging, and (68)Ga-NODAGA-RGD PET for αvβ3 integrin molecular in vivo imaging of spontaneous PDAC occurring in Ptf1a(+/Cre);Kras(+/LSL-G12D);p53(LoxP/LoxP) mice. (NODAGA is 1,4,7-triazacyclononane-1,4-bis[acetic acid]-7-[2-glutaric acid] and RGD is arginine-glycine-aspartic acid.)
  
  
  RESULTS
  αvβ3 integrin is expressed in tumor cells of human and murine PDAC. IntegriSense fluorescence molecular tomography and (68)Ga-NODAGA-RGD PET enabled faithful visualization of PDAC. Furthermore, intraoperative optical imaging with IntegriSense 680 allowed good delineation of tumor borders.
  
  
  CONCLUSIONS
  Imaging approaches targeting αvβ3 integrin expand the potential of molecular imaging for identification of αvβ3-positive PDAC with potential implications in early detection, fluorescence-guided surgery, and therapy monitoring.
authors.affiliation: II. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
authors.forename: Marija
authors.initials: M
authors.lastname: Trajkovic-Arsic
authors.forename: Pouyan
authors.initials: P
authors.lastname: Mohajerani
authors.forename: Athanasios
authors.initials: A
authors.lastname: Sarantopoulos
authors.forename: Evdokia
authors.initials: E
authors.lastname: Kalideris
authors.forename: Katja
authors.initials: K
authors.lastname: Steiger
authors.forename: Irene
authors.initials: I
authors.lastname: Esposito
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Ma
authors.forename: George
authors.initials: G
authors.lastname: Themelis
authors.forename: Neal
authors.initials: N
authors.lastname: Burton
authors.forename: Christoph W
authors.initials: CW
authors.lastname: Michalski
authors.forename: Jörg
authors.initials: J
authors.lastname: Kleeff
authors.forename: Stefan
authors.initials: S
authors.lastname: Stangl
authors.forename: Ambros J
authors.initials: AJ
authors.lastname: Beer
authors.forename: Karolin
authors.initials: K
authors.lastname: Pohle
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Wester
authors.forename: Roland M
authors.initials: RM
authors.lastname: Schmid
authors.forename: Rickmer
authors.initials: R
authors.lastname: Braren
authors.forename: Vasilis
authors.initials: V
authors.lastname: Ntziachristos
authors.forename: Jens T
authors.initials: JT
authors.lastname: Siveke
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000601:surgery; D000818:Animals; D045744:Cell Line, Tumor; D005240:Feasibility Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D007432:Intraoperative Period; D051379:Mice; D064847:Multimodal Imaging; D061848:Optical Imaging; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000601:surgery; D049268:Positron-Emission Tomography; D014054:Tomography
chemical_list: D039302:Integrin alphaVbeta3
keywords: fluorescence molecular tomography; genetically engineered mice; integrin αvβ3; pancreatic cancer; positron emission tomography