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Research ArticleClinical (Oncology: Other)

CD8-Targeted PET Imaging of Tumor-Infiltrating T Cells in Patients with Cancer: A Phase I First-in-Humans Study of 89Zr-Df-IAB22M2C, a Radiolabeled Anti-CD8 Minibody

Michael D. Farwell, Raymond F. Gamache, Hasan Babazada, Matthew D. Hellmann, James J. Harding, Ron Korn, Alessandro Mascioni, William Le, Ian Wilson, Michael S. Gordon, Anna M. Wu, Gary A. Ulaner, Jedd D. Wolchok, Michael A. Postow and Neeta Pandit-Taskar
Journal of Nuclear Medicine May 2022, 63 (5) 720-726; DOI: https://doi.org/10.2967/jnumed.121.262485
Michael D. Farwell
1Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania;
2Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania;
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Raymond F. Gamache
1Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania;
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Hasan Babazada
1Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania;
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Matthew D. Hellmann
3Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, New York;
4Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York;
5Department of Medicine, Weill Cornell Medical College, New York, New York;
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James J. Harding
4Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York;
5Department of Medicine, Weill Cornell Medical College, New York, New York;
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Ron Korn
6Imaging Endpoints, Scottsdale, Arizona;
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Alessandro Mascioni
7ImaginAb, Inc., Inglewood, California;
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William Le
7ImaginAb, Inc., Inglewood, California;
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Ian Wilson
7ImaginAb, Inc., Inglewood, California;
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Michael S. Gordon
8HonorHealth Research Institute, Scottsdale, Arizona;
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Anna M. Wu
7ImaginAb, Inc., Inglewood, California;
9Department of Molecular Imaging and Therapy, Beckman Research Institute of the City of Hope, Duarte, California;
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Gary A. Ulaner
10Molecular Imaging and Therapy, Hoag Family Cancer Institute, Newport Beach, California;
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Jedd D. Wolchok
3Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, New York;
4Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York;
5Department of Medicine, Weill Cornell Medical College, New York, New York;
11Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York;
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Michael A. Postow
4Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York;
5Department of Medicine, Weill Cornell Medical College, New York, New York;
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Neeta Pandit-Taskar
3Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center, New York, New York;
12Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York; and
13Department of Radiology, Weill Cornell Medical College, New York, New York
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  • FIGURE 1.
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    FIGURE 1.

    Serum clearance and biodistribution of 89Zr-Df-IAB22M2C. (A) Serum clearance of 89Zr-Df-IAB22M2C based on enzyme-linked immunosorbent assay measurements (limit of detection = 5 ng/mL). No minibody was detected in serum at the 0.2-mg dose. (B) Whole-body PET images of a patient at various times after injection of 89Zr-Df-IAB22M2C (1.5-mg minibody dose) demonstrating the distribution of 89Zr-Df-IAB22M2C in normal tissues and uptake in a nodal metastasis in the right neck (arrow), with good visualization of uptake in the nodal metastasis at 24–48 h after injection.

  • FIGURE 2.
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    FIGURE 2.

    89Zr-Df-IAB22M2C uptake in normal tissues and tumor lesions versus time. (A) 89Zr-Df-IAB22M2C uptake in CD8-rich reference tissues in patients administered 0.5 and 1.5 mg of minibody mass. (B) 89Zr-Df-IAB22M2C uptake in CD8-poor reference tissues in patients administered 0.5 and 1.5 mg of minibody mass. (C) Box and whisker plots of 89Zr-Df-IAB22M2C uptake in tumor lesions from all subjects (n = 15). Boxes outline first and third quartile values. Median SUVMAX values are indicated by horizontal line and mean SUVMAX values are indicated with +. Outlier values are indicated by dots. (D) 89Zr-Df-IAB22M2C mean tumor uptake in patients who received 0.5 and 1.5 mg of minibody mass. BM = bone marrow; LN = lymph nodes.

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    FIGURE 3.

    A 77-y-old man with metastatic melanoma treated with pembrolizumab. CT and fused 18F-FDG PET/CT images (left) acquired at approximately 8 mo after initiation of immunotherapy demonstrate 2 18F-FDG–avid nodal metastases in right neck (SUVMAX = 8.0, top image; SUVMAX = 16.8, bottom image), which could represent viable metastases. Corresponding CT and fused CD8 PET/CT images (right) obtained at 1 mo after 18F-FDG PET/CT demonstrate significant tracer activity in both metastases (SUVMAX = 5.4, top image; SUVMAX = 14.6, bottom image), which suggests that some of the 18F-FDG activity could be due to tumor-infiltrating CD8+ T cells rather than tumor cells. Follow-up imaging over the next 6 mo demonstrated stable disease, supportive of this hypothesis.

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    FIGURE 4.

    A 71-y-old man with locally advanced stage III melanoma treated with pembrolizumab. Baseline CT and fused 18F-FDG PET/CT images (left) demonstrate 2 18F-FDG–avid metastases in left axilla (SUVMAX = 10.0, medial node; SUVMAX = 7.6, lateral node). CT and fused CD8 PET/CT images (middle) obtained at 28 d after start of immunotherapy demonstrate increased tracer activity in both metastases (SUVMAX = 9.5, medial node; SUVMAX = 10.0, lateral node), suggestive of tumor infiltration by CD8+ T cells. Follow-up imaging with contrast-enhanced CT (right) demonstrated complete response to therapy.

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    TABLE 1.

    Patient Characteristics

    CharacteristicAll patients (n = 15)
    Median age (y)64 (range, Embedded Image)
    Sex (n)
     Male9 (60)
     Female6 (40)
    Tumor type (n)
     Melanoma8 (53)
     Non–small cell lung carcinoma6 (40)
     Hepatocellular carcinoma1 (7)
    Treatment profile at the time of imaging (n)
     On immunotherapy (Embedded Image mo)3 (20)
     On immunotherapy (Embedded Image mo)5 (33)
     On targeted therapy (Embedded Image mo)2 (13)
     Discontinued prior treatment (Embedded Image mo)2 (13)
     Treatment naïve3 (20)
    • Data in parentheses are percentages unless otherwise indicated.

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Journal of Nuclear Medicine: 63 (5)
Journal of Nuclear Medicine
Vol. 63, Issue 5
May 1, 2022
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CD8-Targeted PET Imaging of Tumor-Infiltrating T Cells in Patients with Cancer: A Phase I First-in-Humans Study of 89Zr-Df-IAB22M2C, a Radiolabeled Anti-CD8 Minibody
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CD8-Targeted PET Imaging of Tumor-Infiltrating T Cells in Patients with Cancer: A Phase I First-in-Humans Study of 89Zr-Df-IAB22M2C, a Radiolabeled Anti-CD8 Minibody
Michael D. Farwell, Raymond F. Gamache, Hasan Babazada, Matthew D. Hellmann, James J. Harding, Ron Korn, Alessandro Mascioni, William Le, Ian Wilson, Michael S. Gordon, Anna M. Wu, Gary A. Ulaner, Jedd D. Wolchok, Michael A. Postow, Neeta Pandit-Taskar
Journal of Nuclear Medicine May 2022, 63 (5) 720-726; DOI: 10.2967/jnumed.121.262485

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CD8-Targeted PET Imaging of Tumor-Infiltrating T Cells in Patients with Cancer: A Phase I First-in-Humans Study of 89Zr-Df-IAB22M2C, a Radiolabeled Anti-CD8 Minibody
Michael D. Farwell, Raymond F. Gamache, Hasan Babazada, Matthew D. Hellmann, James J. Harding, Ron Korn, Alessandro Mascioni, William Le, Ian Wilson, Michael S. Gordon, Anna M. Wu, Gary A. Ulaner, Jedd D. Wolchok, Michael A. Postow, Neeta Pandit-Taskar
Journal of Nuclear Medicine May 2022, 63 (5) 720-726; DOI: 10.2967/jnumed.121.262485
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Keywords

  • 89Zr-Df-IAB22M2C
  • PET imaging
  • CD8+ T cell
  • minibody
  • immunotherapy
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