title: Development of a novel preclinical pancreatic cancer research model: bioluminescence image-guided focal irradiation and tumor monitoring of orthotopic xenografts.
abstract: OBJECTIVE
  We report on a novel preclinical pancreatic cancer research model that uses bioluminescence imaging (BLI)-guided irradiation of orthotopic xenograft tumors, sparing of surrounding normal tissues, and quantitative, noninvasive longitudinal assessment of treatment response.
  
  
  METHODS
  Luciferase-expressing MiaPaCa-2 pancreatic carcinoma cells were orthotopically injected in nude mice. BLI was compared to pathologic tumor volume, and photon emission was assessed over time. BLI was correlated to positron emission tomography (PET)/computed tomography (CT) to estimate tumor dimensions. BLI and cone-beam CT (CBCT) were used to compare tumor centroid location and estimate setup error. BLI and CBCT fusion was performed to guide irradiation of tumors using the small animal radiation research platform (SARRP). DNA damage was assessed by γ-H2Ax staining. BLI was used to longitudinally monitor treatment response.
  
  
  RESULTS
  Bioluminescence predicted tumor volume (R = 0.8984) and increased linearly as a function of time up to a 10-fold increase in tumor burden. BLI correlated with PET/CT and necropsy specimen in size (P < .05). Two-dimensional BLI centroid accuracy was 3.5 mm relative to CBCT. BLI-guided irradiated pancreatic tumors stained positively for γ-H2Ax, whereas surrounding normal tissues were spared. Longitudinal assessment of irradiated tumors with BLI revealed significant tumor growth delay of 20 days relative to controls.
  
  
  CONCLUSIONS
  We have successfully applied the SARRP to a bioluminescent, orthotopic preclinical pancreas cancer model to noninvasively: 1) allow the identification of tumor burden before therapy, 2) facilitate image-guided focal radiation therapy, and 3) allow normalization of tumor burden and longitudinal assessment of treatment response.
authors.affiliation: Department of Radiation Oncology & Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Tuli
authors.forename: Andrew
authors.initials: A
authors.lastname: Surmak
authors.forename: Juvenal
authors.initials: J
authors.lastname: Reyes
authors.forename: Amy
authors.initials: A
authors.lastname: Hacker-Prietz
authors.forename: Michael
authors.initials: M
authors.lastname: Armour
authors.forename: Ashley
authors.initials: A
authors.lastname: Leubner
authors.forename: Amanda
authors.initials: A
authors.lastname: Blackford
authors.forename: Erik
authors.initials: E
authors.lastname: Tryggestad
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Jaffee
authors.forename: John
authors.initials: J
authors.lastname: Wong
authors.forename: Theodore L
authors.initials: TL
authors.lastname: Deweese
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Herman