title: Orthotopic pancreatic tumors detected by optoacoustic tomography using Syndecan-1.
abstract: BACKGROUND
  Advances in small animal imaging have improved the detection and monitoring of cancer in vivo; although with orthotopic models, precise localization of tumors remains a challenge. In this study, we evaluated multispectral optoacoustic tomography (MSOT) as an imaging modality to detect pancreatic adenocarcinoma in an orthotopic murine model.
  
  
  METHODS
  In vitro binding of Syndecan-1 probe to the human pancreatic cancer cell line S2VP10 was evaluated on flow cytometry. For in vivo testing, S2VP10 cells were orthotopically implanted into the pancreas of severe combined immunodeficiency mice. At 7 d after implantation, the mice were intravenously injected with Syndecan-1 probe, and tumor uptake was evaluated with MSOT at multiple time points. Comparison was made with a free-dye control, indocyanine green (ICG). Probe uptake was verified ex vivo with fluorescent imaging.
  
  
  RESULTS
  Syndecan-1 probe demonstrated partial binding to S2VP10 cells in vitro. In vivo, Syndecan-1 probe preferentially accumulated in the pancreas tumor (480 MSOT a.u.) compared with off-target organs, including the liver (67 MSOT a.u.) and kidney (96 MSOT a.u.). Syndecan-1 probe accumulation peaked at 6 h (480 MSOT a.u.), whereas the ICG control dye failed to demonstrate similar retention within the tumor bed (0.0003 MSOT a.u.). At peak accumulation, signal intensity was 480 MSOT a.u., resulting in several times greater signal in the tumor bed than in the kidney or liver. Ex vivo fluorescent imaging comparing tumor signal with that within off-target organs confirmed the in vivo results.
  
  
  CONCLUSIONS
  MSOT demonstrates successful accumulation of Syndecan-1 probe within pancreatic tumors, and provides high-resolution images, which allow noninvasive, real-time comparison of signal within individual organs. Syndecan-1 probe preferentially accumulates within a pancreatic adenocarcinoma model, with minimal off-target effects.
authors.affiliation: The Hiram C. Polk Jr., MD Department of Surgery, University of Louisville, Louisville, Kentucky.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Kimbrough
authors.affiliation: Department of Medicine, University of Louisville, Louisville, Kentucky.
authors.forename: Shanice
authors.initials: S
authors.lastname: Hudson
authors.affiliation: Department of Medicine, University of Louisville, Louisville, Kentucky.
authors.forename: Anil
authors.initials: A
authors.lastname: Khanal
authors.affiliation: The Hiram C. Polk Jr., MD Department of Surgery, University of Louisville, Louisville, Kentucky.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Egger
authors.affiliation: Department of Medicine, University of Louisville, Louisville, Kentucky. Electronic address: lrmcna01@exchange.louisville.edu.
authors.forename: Lacey R
authors.initials: LR
authors.lastname: McNally
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging*; D000818:Animals; D045744:Cell Line, Tumor; D004396:Coloring Agents; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007208:Indocyanine Green; D051379:Mice; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging*; D061088:Photoacoustic Techniques / Q000379:methods*; D011859:Radiography; D053668:Syndecan-1 / Q000378:metabolism*; D014054:Tomography / Q000379:methods*
chemical_list: D004396:Coloring Agents; C508241:SDC1 protein, human; D053668:Syndecan-1; D007208:Indocyanine Green
keywords: Multispectral optoacoustic tomography; Pancreatic adenocarcinoma; Syndecan-1; Targeted therapy