Research ArticleBasic Science Investigations

Variability of Proliferation and Diffusion in Different Lung Cancer Models as Measured by 3′-Deoxy-3′-18F-Fluorothymidine PET and Diffusion-Weighted MR Imaging

Sonja Schelhaas, Lydia Wachsmuth, Thomas Viel, Davina J. Honess, Kathrin Heinzmann, Donna-Michelle Smith, Sven Hermann, Stefan Wagner, Michael T. Kuhlmann, Carsten Müller-Tidow, Klaus Kopka, Otmar Schober, Michael Schäfers, Richard Schneider, Eric O. Aboagye, John Griffiths, Cornelius Faber and Andreas H. Jacobs
Journal of Nuclear Medicine June 2014, 55 (6) 983-988; DOI: https://doi.org/10.2967/jnumed.113.133348

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    NSCLC xenografts differ with respect to growth. Tumor size was determined by caliper measurements. n = number of tumors.

  • FIGURE 2.
    FIGURE 2.

    PET imaging of lung cancer xenografts reveals pronounced 18F-FLT uptake in A549 and H1975 xenografts. Transverse slices of 18F-FDG (A) and 18F-FLT (B) PET images at biggest tumor diameter of representative tumors about 4 wk after implantation are shown. Maximum radiotracer uptake of whole tumors was determined. Some tumors were measured several times during their growth (∼2 and 4 wk after implantation). However, no influence of imaging time point was detected, and data were combined in analysis. Blue = A549, red = HTB56, green = EBC1, purple = H1975. n = number of analyses per cell line. Scale bars = 5 mm.

  • FIGURE 3.
    FIGURE 3.

    Proliferation as determined by histologic markers does not positively correlate with 18F-FLT uptake. Histologic sections were probed for Ki67 (A) and BrdU (B). Percentage of specifically stained nuclei was quantified in viable tumor regions. Blue = A549, red = HTB56, green = EBC1, purple = H1975. n = number of tumors analyzed (1 section per tumor). Scale bars = 100 μm.

  • FIGURE 4.
    FIGURE 4.

    Expression of thymidine metabolism proteins does not account for variations in 18F-FLT uptake, except for TP. Tumor homogenates were analyzed by Western blot for expression of hENT1 (A), TK1 (B), TS (C), or TP (D). Five different xenografts per cell line were examined by this method, and representative blot is shown. Same proteins were also detected by immunohistochemistry. Sections of 4 tumors per cell line were analyzed, and representative figures are depicted here. Scale bars = 100 μm.

  • FIGURE 5.
    FIGURE 5.

    Tumor thymidine negatively correlates with 18F-FLT uptake in lung cancer xenografts. Thymidine levels in tumor homogenates were determined by thymidine-specific liquid chromatography–mass spectrometry. Correlation coefficient = −0.682. P < 0.005.

  • FIGURE 6.
    FIGURE 6.

    ADC differs between analyzed xenografts. Transverse slices of ADC images are depicted here, and respective T2w images can be found in Supplemental Figure 2B. Viable tumor regions were defined on these T2w images, and mean ADC was quantified within 1 representative ROI in this area. Blue = A549, red = HTB56, green = EBC1, purple = H1975. n = number of analyzed tumors per cell line. Scale bars = 5 mm.

  • FIGURE 7.
    FIGURE 7.

    ADC in various lung cancer xenografts is not related to cell death but negatively correlates with cell density. Histologic sections were analyzed for active caspase-3 (A) and TUNEL (B). Representative images of viable tumor regions and respective quantifications are shown here. Scale bars = 100 μm. (C) Number of 4′,6-diamidino-2-phenylindole (DAPI)–stained nuclei per field of view (field of view [FOV], 20× resolution; 580 × 460 μm) was determined as measure for cellular density. Transverse sections at biggest tumor diameter were investigated to directly relate findings to respective MR slices. Correlation coefficient = −0.61; P < 0.005; n = number of tumors analyzed. blue = A549, red = HTB56, green = EBC1, purple = H1975.

Additional Files

Back to top

In this issue

Print
Download PDF
Article Alerts
Email Article
Citation Tools
Bookmark this article

Jump to section

Keywords