Research ArticleBasic Science Investigations

PET of HER2-Positive Pulmonary Metastases with 18F-ZHER2:342 Affibody in a Murine Model of Breast Cancer: Comparison with 18F-FDG

Gabriela Kramer-Marek, Marcelino Bernardo, Dale O. Kiesewetter, Ulas Bagci, Monika Kuban, Aras Omer, Rafal Zielinski, Jurgen Seidel, Peter Choyke and Jacek Capala
Journal of Nuclear Medicine June 2012, 53 (6) 939-946; DOI: https://doi.org/10.2967/jnumed.111.100354

Article Figures & Data

Figures

  • FIGURE 1.
    FIGURE 1.

    BLI monitoring of metastasis growth. (A) Strong linear correlation (R2 = 0.99) was found between absolute MDA-MB-231HER2-Luc cell number and BLI signal. (B) Total photon flux from BLI signals acquired 9 wk after intravenous injection of MDA-MB-231HER2-Luc cells. Highest ROI signal from either ventral or dorsal position is presented for each individual mouse. Animals indicated by oval shapes were chosen for further imaging studies. (C) Metastasis progression between 9 and 10 wk after cell injection. (D) Representative in vivo images of lungs of mouse number two 10 wk after cell injection.

  • FIGURE 2.
    FIGURE 2.

    Contiguous axial PET/MRI sections of mouse 2 collected 9 and 10 wk after cells injection showing rapid metastasis progression. HER2-positive lung metastases were visualized with high tumor-to-background ratio 1 h after 18F-ZHER2:342-Affibody injection. Tracer uptake 10 wk after cell inoculation, indicated by white arrows, was as follows: 6.2 %ID/g (lesion 1), 6.9 %ID/g (lesion 2), and 3.4 %ID/g (lesion 3). TBR = tumor-to-background ratio.

  • FIGURE 3.
    FIGURE 3.

    Representative autoradiography (left) with corresponding H&E staining (right) of lung tissue sections of mouse 2 injected with 18F-ZHER2:342-Affibody. Arrows indicate tumor nodules. HER2 expression is heterogeneous. N = normal lung tissue.

  • FIGURE 4.
    FIGURE 4.

    Contiguous transaxial PET/CT section of HER2-positive lung metastasis of mouse 2 at 1 h after 18F-FDG injection. Images were collected 9 and 10 wk after cells injection. Increased background activity made evaluation of small pulmonary nodules difficult. Heart and interscapular brown fat had prominent uptake that probably interfered with detection and delineation of most lesions.

  • FIGURE 5.
    FIGURE 5.

    Automated segmentation of tumor lesions from MRI slices acquired 10 wk after tumor cells inoculation. Six slices are arranged such that first column shows original images, second column shows delineated tumor regions, and last column shows fused delineated regions onto MR images. Corresponding intensity and geometry-based features are listed in Table 2.

  • FIGURE 6.
    FIGURE 6.

    H&E (top) and anti-HER2 (bottom) staining of lung tissue slices.

Tables

  • TABLE 1

    Percentage of HER2 Immunohistochemistry Scoring from Overall Metastasis Areas That Were Annotated

    HER2 score
    Animal no.(3+) % cells(2+) % cells(1+) % cells(0+) % cells
    416.414.432.836.4
    54.511.438.845.3
    104.411.940.842.9
    1115.615.941.826.6
    257.49.129.254.3

    • For scoring, Aperio algorithm was used. Scoring system is same as for clinical HercepTest.

  • TABLE 2

    Quantitative Measurements of Segmented Lesions Acquired by MRI

    Maximum intensity (8-bit scale: 0–255) (wk)Mean intensity (wk)Area (mm2) (wk)
    Slice no.910910910
    23809527.5832.2011.5015.39
    2519215276.4356.0915.1319.16
    6786039.5331.661.262.46

    • Maximum and mean intensity levels, size of lesions, and geometry of segmented regions are shown.

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