title: Computed tomography imaging of primary lung cancer in mice using a liposomal-iodinated contrast agent.
abstract: OBJECTIVE
  To investigate the utility of a liposomal-iodinated nanoparticle contrast agent and computed tomography (CT) imaging for characterization of primary nodules in genetically engineered mouse models of non-small cell lung cancer.
  
  
  METHODS
  Primary lung cancers with mutations in K-ras alone (Kras(LA1)) or in combination with p53 (LSL-Kras(G12D);p53(FL/FL)) were generated. A liposomal-iodine contrast agent containing 120 mg Iodine/mL was administered systemically at a dose of 16 µl/gm body weight. Longitudinal micro-CT imaging with cardio-respiratory gating was performed pre-contrast and at 0 hr, day 3, and day 7 post-contrast administration. CT-derived nodule sizes were used to assess tumor growth. Signal attenuation was measured in individual nodules to study dynamic enhancement of lung nodules.
  
  
  RESULTS
  A good correlation was seen between volume and diameter-based assessment of nodules (R(2)>0.8) for both lung cancer models. The LSL-Kras(G12D);p53(FL/FL) model showed rapid growth as demonstrated by systemically higher volume changes compared to the lung nodules in Kras(LA1) mice (p<0.05). Early phase imaging using the nanoparticle contrast agent enabled visualization of nodule blood supply. Delayed-phase imaging demonstrated significant differential signal enhancement in the lung nodules of LSL-Kras(G12D);p53(FL/FL) mice compared to nodules in Kras(LA1) mice (p<0.05) indicating higher uptake and accumulation of the nanoparticle contrast agent in rapidly growing nodules.
  
  
  CONCLUSIONS
  The nanoparticle iodinated contrast agent enabled visualization of blood supply to the nodules during the early-phase imaging. Delayed-phase imaging enabled characterization of slow growing and rapidly growing nodules based on signal enhancement. The use of this agent could facilitate early detection and diagnosis of pulmonary lesions as well as have implications on treatment response and monitoring.
authors.affiliation: Center for In Vivo Microscopy, Duke University Medical Center, Durham, North Carolina, United States of America. cristian.badea@duke.edu
authors.forename: Cristian T
authors.initials: CT
authors.lastname: Badea
authors.forename: Khannan K
authors.initials: KK
authors.lastname: Athreya
authors.forename: Gabriela
authors.initials: G
authors.lastname: Espinosa
authors.forename: Darin
authors.initials: D
authors.lastname: Clark
authors.forename: A Paiman
authors.initials: AP
authors.lastname: Ghafoori
authors.forename: Yifan
authors.initials: Y
authors.lastname: Li
authors.forename: David G
authors.initials: DG
authors.lastname: Kirsch
authors.forename: G Allan
authors.initials: GA
authors.lastname: Johnson
authors.forename: Ananth
authors.initials: A
authors.lastname: Annapragada
authors.forename: Ketan B
authors.initials: KB
authors.lastname: Ghaghada
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000473:pathology; D003287:Contrast Media; D008081:Liposomes; D008175:Lung Neoplasms / Q000098:blood supply / Q000000981:diagnostic imaging* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D053758:Nanoparticles; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D014057:Tomography, X-Ray Computed; D014283:Triiodobenzoic Acids; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D003287:Contrast Media; D008081:Liposomes; D014283:Triiodobenzoic Acids; D016159:Tumor Suppressor Protein p53; D016283:Proto-Oncogene Proteins p21(ras); C044834:iodixanol