Computed tomography imaging of primary lung cancer in mice using a liposomal-iodinated contrast agent.

Abstract

PURPOSE: 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.

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Citation

Published Version (Please cite this version)

10.1371/journal.pone.0034496

Publication Info

Badea, CT, KK Athreya, G Espinosa, D Clark, AP Ghafoori, Y Li, DG Kirsch, GA Johnson, et al. (2012). Computed tomography imaging of primary lung cancer in mice using a liposomal-iodinated contrast agent. PLoS One, 7(4). p. e34496. 10.1371/journal.pone.0034496 Retrieved from https://hdl.handle.net/10161/16171.

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Scholars@Duke

Badea

Cristian Tudorel Badea

Professor in Radiology

  • Our lab's research focus lies primarily in developing novel quantitative imaging systems, reconstruction algorithms and analysis methods.  My major expertise is in preclinical CT.
  • Currently, we are particularly interested in developing novel strategies for spectral CT imaging using nanoparticle-based contrast agents for theranostics (i.e. therapy and diagnostics).
  • We are also engaged in developing new approaches for multidimensional CT image reconstruction suitable to address difficult undersampling cases in cardiac and spectral CT (dual energy and photon counting) using compressed sensing and/or deep learning.


Clark

Darin Clark

Assistant Professor in Radiology
Kirsch

David Guy Kirsch

Adjunct Professor in the Department of Radiation Oncology

My clinical interests are the multi-modality care of patients with bone and soft tissue sarcomas and developing new sarcoma therapies. My laboratory interests include utilizing mouse models of cancer to study cancer and radiation biology in order to develop new cancer therapies in the pre-clinical setting.

Johnson

G. Allan Johnson

Charles E. Putman University Distinguished Professor of Radiology

Dr. Johnson is the Charles E. Putman University Professor of Radiology, Professor of Physics, and Biomedical Engineering, and Director of the Duke Center for In Vivo Microscopy (CIVM). The CIVM is an NIH/NIBIB national Biomedical Technology Resource Center with a mission to develop novel technologies for preclinical imaging (basic sciences) and apply the technologies to critical biomedical questions. Dr. Johnson was one of the first researchers to bring Paul Lauterbur's vision of magnetic resonance (MR) microscopy to practice as described in his paper, "Nuclear magnetic resonance imaging at microscopic resolution" (J Magn Reson 68:129-137, 1986). Dr. Johnson is involved in both the engineering physics required to extend the resolution of MR imaging and in a broad range of applications in the basic sciences.


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