10 research outputs found
Computed Tomography Imaging of Primary Lung Cancer in Mice Using a Liposomal-Iodinated Contrast Agent
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.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.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.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
Orthgonal thick slab maximum intensity projection (MIP) images demonstrating visualization of nodule blood supply in the lung cancer models.
<p>The images were acquired immediately after administration of liposomal contrast agent.</p
Hematoxylin and eosin staining showing characteristics of high-grade lung cancer in LSL-Kras<sup>G12D</sup>;<sup>p53FL/FL</sup> mice with pleomorphic nuclei (a,b) and low-grade Kras<sup>LA1</sup> lung tumors in Kras<sup>LA1</sup> mice with regular nuclei and minimal cytologic atypia (c,d).
<p>Images were acquired at 10× (a,c) and 40× magnification (c,d). Scale bars: 200 um in a and c; 100 um in b and d.</p
Correlation between nodule volume and diameter in LSL-Kras<sup>G12D</sup>;p53<sup>FL/FL</sup> (•) and Kras<sup>LA1</sup> (×) models.
<p>(<b>a</b>)<b>.</b> Solid lines indicate cubic fit to the data points. An R<sup>2</sup> value of 0.93 and 0.81 was obtained for LSL-Kras<sup>G12D</sup>;p53<sup>FL/FL</sup> and Kras<sup>LA1</sup> models, respectively. Percentage change in nodule volume in the two lung cancer models as a function of nodule diameter (* indicates p<0.05) (b). CT-derived fractional blood volume as a function of nodule diameter (c).</p
Representative coronal micro-CT images of LSL-Kras<sup>G12D</sup>;p53<sup>FL/FL</sup> and Kras<sup>LA1</sup> mice before liposomal contrast-agent injection and at 0 hr, Day 3 and Day 7 post-contrast injection.
<p>Note the differential enhancement of tumors at Day 7 post-contrast time point in the LSL-Kras<sup>G12D</sup>;p53<sup>FL/FL</sup> lesions only.</p
Differential signal enhancement on day 7 in the two primary lung cancer nodules.
<p>(* indicates p<0.05).</p
Dynamic signal enhancement in (a) blood and (b) nodules, in the two primary lung cancer models. Errors bars represent standard deviations (* indicates p<0.05).
<p>Dynamic signal enhancement in (a) blood and (b) nodules, in the two primary lung cancer models. Errors bars represent standard deviations (* indicates p<0.05).</p