Research ArticleBasic Science Investigations

Biomarkers for Radiation Pneumonitis Using Noninvasive Molecular Imaging

Meetha Medhora, Steven Haworth, Yu Liu, Jayashree Narayanan, Feng Gao, Ming Zhao, Said Audi, Elizabeth R. Jacobs, Brian L. Fish and Anne V. Clough
Journal of Nuclear Medicine August 2016, 57 (8) 1296-1301; DOI: https://doi.org/10.2967/jnumed.115.160291

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    Typical 99mTc-MAA (left) and 99mTc-Duramycin (right) transaxial slices from reconstructed volumes obtained from control (top) and 15-Gy–irradiated (bottom) rats. Color images represent segmented SPECT lung region coregistered with gray-scale CT images.

  • FIGURE 2.
    FIGURE 2.

    Decrease in perfused pulmonary volume by radiation, as determined by ratio of 99mTc-MAA SPECT perfused volume to coregistered CT anatomic volume. Line is median value in nonirradiated rats (no rads; n = 12) and irradiated rats at 1 wk (n = 8), 2 wk (n = 10), 3 wk (n = 13), and 4 wk (n = 9) after 15 Gy to thorax. *P < 0.05 vs. nonirradiated controls.

  • FIGURE 3.
    FIGURE 3.

    Increase in 99mTc-Duramycin lung uptake in irradiated lungs vs. controls. Line is median value in nonirradiated rats (no rads; n = 12) and irradiated rats at 1 wk (n = 5), 2 wk (n = 11), and 3 wk (n = 5) after 15 Gy to thorax. *P < 0.05 vs. control. **P < 0.05 vs. 15 Gy at 1 wk.

  • FIGURE 4.
    FIGURE 4.

    Increase in apoptotic cells in lung as determined by cleaved caspase 3+ cells using immunohistochemistry. Apoptotic cells per field in nonirradiated and irradiated rats are shown at 1, 2, 3, and 4 wk after 15 Gy to thorax. Line is median value in nonirradiated rats (no rads; n = 15) and irradiated rats (n = 8 per group). *P < 0.05 vs. control.

  • FIGURE 5.
    FIGURE 5.

    Histologic analysis showing increase in alveolar wall thickness and macrophages after 15 Gy of whole-thorax irradiation. Representative fields are shown of hematoxylin- and eosin-stained lung sections from nonirradiated lung (A), lung 2 wk after 15 Gy (B), and lung 4 wk after 15 Gy (C). Solid arrow points to macrophages, dashed arrow to thickened alveolar wall. (D) Scores for alveolar wall thickness. (E) Counts for foamy macrophages. (F) Counts for CD68+ macrophages. Line is median value in nonirradiated rats (n = 16 each for D and E and 8 for F) and irradiated rats (n = 8 each for D, E, and F). *P < 0.05 vs. control at 4 wk.

  • FIGURE 6.
    FIGURE 6.

    Increase in pulmonary vascular resistance and permeability (Kf) in isolated perfused lungs 2 wk after irradiation with 15 Gy. Line is mean value (n = 5 rats per group). No rads = nonirradiated rats. *P < 0.05 (top) or < 0.001 (bottom) vs. control.

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