title: Optical imaging of CCK₂/gastrin receptor-positive tumors with a minigastrin near-infrared probe.
abstract: OBJECTIVE
  A variety of tumors in different organs with good accessibility to near-infrared light express the cholecystokinin-2 (CCK₂)/gastrin receptor. Therefore, the applicability of fluorescence optical imaging was assessed using a novel peptide probe.
  
  
  METHODS
  This study was approved by the regional animal committee. Our optical peptide probe (DY-minigastrin) was synthesized by coupling a hemicyanine dye to a gastrin derivative peptide (minigastrin). In vitro CCK₂/gastrin receptor identification was performed in receptor-positive HT-29 and negative A-375 cells using flow cytometry, laser scanning microscopy, and macroscopic near-infrared fluorescent (NIRF) imaging. For in vivo studies, tumor cells were implanted into mice, and DY-minigastrin in presence or absence of nonlabeled minigastrin (control of signaling specificity) was applied intravenously. Fluorescence signals in tumors and organs were recorded and statistically analyzed.
  
  
  RESULTS
  Flow cytometry, laser scanning microscopy, and in vitro macroscopic imaging of cell pellets revealed a distinct accumulation of our minigastrin probe in HT-29 cells, showing distinct probe internalization. In vivo NIRF whole-body animal imaging, again, demonstrated a clear depiction of HT-29 tumors, which was reversed by blocking with nonlabeled minigastrin. Semi-quantitative fluorescence analysis and histologic observations were in agreement with these observations. A distinct probe organ distribution was observed.
  
  
  CONCLUSIONS
  Our observations indicate that DY-minigastrin-based NIRF optical imaging of CCK₂/gastrin receptor protein is feasible. Because of its widespread occurrence in different tumor types, endoscopic, laparoscopic, and tomographic receptor imaging could be accomplished in the near future.
authors.affiliation: Department of Experimental Radiology, Institute of Diagnostic and Interventional Radiology, University Hospital Jena, Jena, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Laabs
authors.forename: Martin
authors.initials: M
authors.lastname: Béhé
authors.forename: Susanne
authors.initials: S
authors.lastname: Kossatz
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Frank
authors.forename: Werner A
authors.initials: WA
authors.lastname: Kaiser
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hilger
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005240:Feasibility Studies; D005434:Flow Cytometry; D005755:Gastrins; D019073:HT29 Cells / Q000378:metabolism; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000175:diagnosis* / Q000473:pathology; D012333:RNA, Messenger; D043887:Receptor, Cholecystokinin B / Q000378:metabolism*
chemical_list: D005755:Gastrins; D012333:RNA, Messenger; D043887:Receptor, Cholecystokinin B; C008530:minigastrin