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Research ArticleFEATURED ARTICLE OF THE MONTH
Open Access

Human Epidermal Growth Factor Receptor 2–Targeting [68Ga]Ga-ABY-025 PET/CT Predicts Early Metabolic Response in Metastatic Breast Cancer

Ali Alhuseinalkhudhur, Henrik Lindman, Per Liss, Tora Sundin, Fredrik Y. Frejd, Johan Hartman, Victor Iyer, Joachim Feldwisch, Mark Lubberink, Caroline Rönnlund, Vladimir Tolmachev, Irina Velikyan and Jens Sörensen
Journal of Nuclear Medicine September 2023, 64 (9) 1364-1370; DOI: https://doi.org/10.2967/jnumed.122.265364
Ali Alhuseinalkhudhur
1Division of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden;
2Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden;
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Henrik Lindman
2Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden;
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Per Liss
3Division of Radiology, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden;
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Tora Sundin
4Clinical Research and Development Unit, Uppsala University Hospital, Uppsala, Sweden;
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Fredrik Y. Frejd
2Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden;
5Affibody AB, Solna, Sweden;
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Johan Hartman
6Department of Oncology–Pathology, Karolinska Institute, Stockholm, Sweden;
7Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden; and
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Victor Iyer
1Division of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden;
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Joachim Feldwisch
5Affibody AB, Solna, Sweden;
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Mark Lubberink
1Division of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden;
8Department of Medical Physics, Uppsala University Hospital, Uppsala, Sweden
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Caroline Rönnlund
6Department of Oncology–Pathology, Karolinska Institute, Stockholm, Sweden;
7Department of Clinical Pathology and Cancer Diagnostics, Karolinska University Hospital, Stockholm, Sweden; and
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Vladimir Tolmachev
2Department of Immunology, Genetics, and Pathology, Uppsala University, Uppsala, Sweden;
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Irina Velikyan
1Division of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden;
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Jens Sörensen
1Division of Nuclear Medicine and PET, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden;
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  • FIGURE 1.
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    FIGURE 1.

    Diagram of recruitment and diagnostic classification of study subjects, according to the Standards for Reporting Diagnostic Accuracy. BC = breast cancer; ABY = [68Ga]Ga-ABY-025; IHC = immunohistochemistry.

  • FIGURE 2.
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    FIGURE 2.

    Color-coded clinical response in patients with breast cancer. x-axis is HER2 status according to immunohistochemistry with ISH from trial biopsies (n = 40). y-axis is corresponding uptake in biopsied lesions using [68Ga]Ga-ABY-025 PET/CT. Red line indicates SUVmax of 6.0. BC = breast cancer.

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    FIGURE 3.

    [68Ga]Ga-ABY-025 PET/CT and [18F]F-FDG PET/CT images at baseline with [18F]F-FDG PET/CT follow-up after 2 cycles of treatment in biopsy-confirmed HER2-positive disease. (A) Patient with high [68Ga]Ga-ABY-025 uptake (SUVmax, 21), who previously received 3 lines of treatment. [18F]F-FDG PET/CT follow-up showed complete metabolic response. (B) Patient with low uptake (SUVmax, 5.4), who previously received 3 lines of treatment. [18F]F-FDG PET/CT follow-up showed disease progression (Δ-TLG, +68%) despite HER2-targeted treatment. (C) Patient with heterogeneous [68Ga]Ga-ABY-025 uptake, who previously received 7 lines of treatment. [18F]F-FDG PET/CT follow-up showed heterogeneous response, with lesions higher in [68Ga]Ga-ABY-025 uptake tending to have better response. Arrows indicate biopsy sites.

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    FIGURE 4.

    Receiver operating characteristic curve analysis of positive metabolic response after 2 cycles of HER2-targeted treatment in breast cancer patients according to [68Ga]Ga-ABY-025 uptake. Optimal SUVmax cutoff (red circle and diamonds) was 6.0 (n = 47; P = 0.01) in soft-tissue metastases (green line), 16.2 (n = 28; P = 0.003) in skeletal metastases (blue line), and 10.7 (n = 133, P = 0.03) in all lesions (black line). Sensitivity and specificity were 86% and 67%, 69% and 83%, and 56% and 66%, respectively. Red line represents receiver operating curve for random guess. At least 25% reduction in Δ-TLG was considered metabolic response. AUC = area under curve.

  • FIGURE 5.
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    FIGURE 5.

    Number of previous treatments and their effect on response rate measured as Δ-TLG after 2 cycles of HER2-targeted treatment. One-way ANOVA showed significantly different response rates among 3 groups (P < 0.0001). Marker size reflects statistical weight of lesions per patient. P values represent Wilcoxon signed-rank test with regard to metabolic response among 3 groups.

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    TABLE 1.

    Patient Characteristics and Descriptive Data

    HER2 status*
    ParameterPositive cases (n = 31)Negative cases (n = 6)Borderline cases (n = 3)
    Median age (y)57 (29–89)63 (45–78)58 (53–62)
    Estrogen receptor–positive (≥10%)14 (45%)4 (67%)2 (67%)
    Stage
     II14 (45%)01 (33%)
     III2 (7%)1 (17%)0
     IV15 (48%)5 (83%)2 (67%)
    Molecular subtype
     Luminal A1 (17%)
     Luminal B3 (50%)2 (67%)
     HER2-positive17 (55%)
     HER2-positive/luminal14 (45%)
     Triple-negative2 (33%)1 (33%)
    Neoadjuvant treatment
     Primary15 (48%)1 (17%)
     Metastatic2 (6%)1 (33%)
    Previous treatments
    PBC
     None17 (55%)1 (17%)1 (33%)
    MBC
     None1 (33%)
     11 (3%)1 (17%)0
     25 (16%)2 (33%)0
     33 (10%)00
     42 (6%)1 (17%)0
     51 (3%)1 (17%)0
     6+2 (6%)01 (33%)
    • ↵* Based on immunohistochemistry and ISH results.

    • Qualitative data are number and percentage; continuous data are median and range.

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    TABLE 2.

    Anatomic Distribution and [68Ga]Ga-ABY-025 Mean SUVmax for Lesions Used in This Study

    HER2 status
    Positive (n = 31)Negative (n = 6)Borderline (n = 3)
    Site of diseaseNumberSUVmaxNumberSUVmaxNumberSUVmax
    Breast26 (18)10.1 ± 6.93 (1)6.0 ± 2.42 (2)6.8 ± 3.1
    Axilla22 (2)10.9 ± 6.329.0 ± 3.7—
    Liver5 (3)13.7 ± 66 (3)18.1 ± 72 (1)12.6 ± 10.5
    Lung or distal lymph nodes24 (5)9.1 ± 7.435.3 ± 4.9—
    Bone16 (3)16.2 ± 6.19 (1)28 ± 14411.9 ± 4.5
    Other815.8 ± 172 (1)3.9 ± 0.4—
    • Number of biopsied lesions is in parentheses, 1 per patient. SUVmax is mean ± SD.

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Journal of Nuclear Medicine: 64 (9)
Journal of Nuclear Medicine
Vol. 64, Issue 9
September 1, 2023
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Human Epidermal Growth Factor Receptor 2–Targeting [68Ga]Ga-ABY-025 PET/CT Predicts Early Metabolic Response in Metastatic Breast Cancer
Ali Alhuseinalkhudhur, Henrik Lindman, Per Liss, Tora Sundin, Fredrik Y. Frejd, Johan Hartman, Victor Iyer, Joachim Feldwisch, Mark Lubberink, Caroline Rönnlund, Vladimir Tolmachev, Irina Velikyan, Jens Sörensen
Journal of Nuclear Medicine Sep 2023, 64 (9) 1364-1370; DOI: 10.2967/jnumed.122.265364

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Human Epidermal Growth Factor Receptor 2–Targeting [68Ga]Ga-ABY-025 PET/CT Predicts Early Metabolic Response in Metastatic Breast Cancer
Ali Alhuseinalkhudhur, Henrik Lindman, Per Liss, Tora Sundin, Fredrik Y. Frejd, Johan Hartman, Victor Iyer, Joachim Feldwisch, Mark Lubberink, Caroline Rönnlund, Vladimir Tolmachev, Irina Velikyan, Jens Sörensen
Journal of Nuclear Medicine Sep 2023, 64 (9) 1364-1370; DOI: 10.2967/jnumed.122.265364
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Keywords

  • [68Ga]Ga-ABY-025
  • breast cancer
  • HER2 positive
  • affibody molecules
  • PET/CT
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