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Research ArticleBasic Science Investigations

Immuno-PET Imaging of CD30-Positive Lymphoma Using 89Zr-Desferrioxamine–Labeled CD30-Specific AC-10 Antibody

Svetlana N. Rylova, Luigi Del Pozzo, Cathrin Klingeberg, Roswitha Tönnesmann, Anna L. Illert, Philipp T. Meyer, Helmut R. Maecke and Jason P. Holland
Journal of Nuclear Medicine January 2016, 57 (1) 96-102; DOI: https://doi.org/10.2967/jnumed.115.162735
Svetlana N. Rylova
1German Cancer Consortium, Heidelberg, Germany
2Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany
3German Cancer Research Center, Heidelberg, Germany; and
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Luigi Del Pozzo
1German Cancer Consortium, Heidelberg, Germany
2Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany
3German Cancer Research Center, Heidelberg, Germany; and
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Cathrin Klingeberg
1German Cancer Consortium, Heidelberg, Germany
3German Cancer Research Center, Heidelberg, Germany; and
4Department of Internal Medicine I, University Hospital Freiburg, Freiburg, Germany
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Roswitha Tönnesmann
2Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany
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Anna L. Illert
1German Cancer Consortium, Heidelberg, Germany
3German Cancer Research Center, Heidelberg, Germany; and
4Department of Internal Medicine I, University Hospital Freiburg, Freiburg, Germany
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Philipp T. Meyer
1German Cancer Consortium, Heidelberg, Germany
2Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany
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Helmut R. Maecke
2Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany
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Jason P. Holland
1German Cancer Consortium, Heidelberg, Germany
2Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany
3German Cancer Research Center, Heidelberg, Germany; and
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  • Article
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  • FIGURE 1.
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    FIGURE 1.

    (A) Flow cytometry data showing specific binding of AC-10 and DFO-AC-10 to CD30-positive Karpas 299 cells. (B) Control data showing that AC-10 antibody does not bind to CD30-negative A-431 cells. FL = ▪▪▪; PE = phycoerythrin.

  • FIGURE 2.
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    FIGURE 2.

    (A) Size-exclusion radio–high-performance liquid chromatograms showing radiochemical purity of formulated sample of 89Zr-DFO-AC-10. (B and C) Size-exclusion radio–high-performance liquid chromatogram data showing radiochemical stability of 89Zr-DFO-AC-10 after incubation at 37°C in human and mouse sera. DTPA = diethylenetriaminepentaacetic acid.

  • FIGURE 3.
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    FIGURE 3.

    Cellular uptake data showing saturation of specific binding of 89Zr-DFO-AC-10 to CD30-positive Karpas 299 cells and lack of binding to CD30-negative A-431 cells.

  • FIGURE 4.
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    FIGURE 4.

    Biodistribution data showing accumulation and retention of 89Zr-DFO-AC-10 radioactivity in various tissues vs. time in mice bearing either A-431 or Karpas 299 tumors.

  • FIGURE 5.
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    FIGURE 5.

    Longitudinal maximum-intensity-projection PET images showing distribution of 89Zr-DFO-AC-10 in Karpas 299 and A-431 tumor-bearing mice 24–144 h after administration. Mean tumor-to-muscle (T/M) ratios derived from volume-of-interest analysis of PET images are given. In A-431 model, liver and tumor time–activity curves overlap. T/M = tumor-to-muscle ratio.

  • FIGURE 6.
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    FIGURE 6.

    Time–activity curves derived by VOI analysis of immuno-PET/CT images showing mean %IA/g tissue uptake vs. time for 89Zr-DFO-AC-10 radiotracer accumulation in mice bearing either Karpas 299 (A) or A-431 (B) tumors.

  • FIGURE 7.
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    FIGURE 7.

    (A) PET/CT images of 2 representative mice bearing CD30-negative A-431 and CD30-positive Karpas 299 tumors at 144 h after injection. (B) Digital autoradiography and histology data showing accumulation and intratissue distribution of 89Zr-DFO-AC-10 in tumor and liver for both CD30-positive and CD30-negative models. H&E = hematoxylin and eosin. DAR = digital autoradiography; UPP = ▪▪▪.

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    TABLE 1

    Biodistribution of 89Zr-DFO-AC-10 in Nude Mice Bearing Karpas 299 or A-431 Tumors

    A-431 CD30-negativeKarpas 299 CD30-positive
    Site24 h (n = 3)72 h (n = 3)24 h (n = 4)72 h (n = 3)72 h, blocking* (n = 3)
    Blood15.83 ± 2.2712.23 ± 2.189.89 ± 2.706.38 ± 0.469.49 ± 2.60
    Heart4.35 ± 1.273.11 ± 0.882.88 ± 0.361.71 ± 0.222.64 ± 0.47
    Lung6.58 ± 1.155.81 ± 1.074.60 ± 0.873.63 ± 0.594.12 ± 1.20
    Liver10.90 ± 2.1012.61 ± 2.2015.22 ± 1.7111.78 ± 2.4311.00 ± 2.32
    Spleen7.20 ± 1.408.21 ± 2.878.78 ± 2.148.15 ± 0.797.07 ± 0.46
    Pancreas1.68 ± 0.341.24 ± 0.301.05 ± 0.070.66 ± 0.060.74 ± 0.23
    Stomach1.52 ± 0.401.49 ± 0.201.09 ± 0.170.83 ± 0.050.83 ± 0.08
    Small intestine2.09 ± 0.441.82 ± 0.201.23 ± 0.201.12 ± 0.071.12 ± 0.36
    Kidney6.55 ± 1.086.28 ± 0.999.41 ± 1.784.22 ± 0.514.95 ± 0.86
    Muscle1.08 ± 0.190.91 ± 0.100.62 ± 0.060.49 ± 0.100.62 ± 0.20
    Bone2.58 ± 0.534.11 ± 2.732.12 ± 0.485.06 ± 0.382.46 ± 0.65
    Tumor8.23 ± 1.5811.04 ± 0.4027.21 ± 5.9637.92 ± 8.2222.54 ± 1.58
    Tumor/blood0.52 ± 0.120.90 ± 0.162.75 ± 0.965.95 ± 1.362.37 ± 0.67
    Tumor/liver0.76 ± 0.210.88 ± 0.161.79 ± 0.443.22 ± 0.962.05 ± 0.45
    Tumor/kidney1.14 ± 0.311.34 ± 0.472.89 ± 0.849.00 ± 2.234.56 ± 0.85
    Tumor/spleen1.26 ± 0.321.76 ± 0.283.10 ± 1.014.65 ± 1.103.19 ± 0.31
    Tumor/muscle7.63 ± 2.0012.09 ± 1.4543.95 ± 10.6777.24 ± 22.9236.21 ± 11.85
    Tumor/bone3.20 ± 0.902.68 ± 1.7912.82 ± 4.037.49 ± 1.729.18 ± 2.51
    • ↵* With 500-μg mAb blocking.

    • Data are mean %IA/g ± SD. Errors for tumor-to-tissue ratios are geometric mean of SD.

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Journal of Nuclear Medicine: 57 (1)
Journal of Nuclear Medicine
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January 1, 2016
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Immuno-PET Imaging of CD30-Positive Lymphoma Using 89Zr-Desferrioxamine–Labeled CD30-Specific AC-10 Antibody
Svetlana N. Rylova, Luigi Del Pozzo, Cathrin Klingeberg, Roswitha Tönnesmann, Anna L. Illert, Philipp T. Meyer, Helmut R. Maecke, Jason P. Holland
Journal of Nuclear Medicine Jan 2016, 57 (1) 96-102; DOI: 10.2967/jnumed.115.162735

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Immuno-PET Imaging of CD30-Positive Lymphoma Using 89Zr-Desferrioxamine–Labeled CD30-Specific AC-10 Antibody
Svetlana N. Rylova, Luigi Del Pozzo, Cathrin Klingeberg, Roswitha Tönnesmann, Anna L. Illert, Philipp T. Meyer, Helmut R. Maecke, Jason P. Holland
Journal of Nuclear Medicine Jan 2016, 57 (1) 96-102; DOI: 10.2967/jnumed.115.162735
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