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Research ArticleOncology

First-in-Humans Imaging with 89Zr-Df-IAB22M2C Anti-CD8 Minibody in Patients with Solid Malignancies: Preliminary Pharmacokinetics, Biodistribution, and Lesion Targeting

Neeta Pandit-Taskar, Michael A. Postow, Matthew D. Hellmann, James J. Harding, Christopher A. Barker, Joseph A. O’Donoghue, Martha Ziolkowska, Shutian Ruan, Serge K. Lyashchenko, Frank Tsai, Michael Farwell, Tara C. Mitchell, Ron Korn, William Le, Jason S. Lewis, Wolfgang A. Weber, Deepak Behera, Ian Wilson, Michael Gordon, Anna M. Wu and Jedd D. Wolchok
Journal of Nuclear Medicine April 2020, 61 (4) 512-519; DOI: https://doi.org/10.2967/jnumed.119.229781
Neeta Pandit-Taskar
1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
2Department of Radiology, Weill Cornell Medical College, New York, New York
3Parker Institute for Cancer Immunotherapy, 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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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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Christopher A. Barker
6Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
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Joseph A. O’Donoghue
7Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York
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Martha Ziolkowska
1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
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Shutian Ruan
1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
2Department of Radiology, Weill Cornell Medical College, New York, New York
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Serge K. Lyashchenko
8Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York
9Radiochemistry and Molecular Imaging Probes Core, Memorial Sloan Kettering Cancer Center, New York, New York
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Frank Tsai
10Honor Health, Scottsdale, Arizona
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Michael Farwell
11University of Pennsylvania, Philadelphia, Pennsylvania
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Tara C. Mitchell
11University of Pennsylvania, Philadelphia, Pennsylvania
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Ron Korn
12Imaging Endpoints, Scottsdale, Arizona
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William Le
13ImaginAb, Inc., Inglewood, California; and
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Jason S. Lewis
1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
8Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York
9Radiochemistry and Molecular Imaging Probes Core, Memorial Sloan Kettering Cancer Center, New York, New York
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Wolfgang A. Weber
1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York
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Deepak Behera
13ImaginAb, Inc., Inglewood, California; and
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Ian Wilson
13ImaginAb, Inc., Inglewood, California; and
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Michael Gordon
10Honor Health, Scottsdale, Arizona
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Anna M. Wu
13ImaginAb, Inc., Inglewood, California; and
14Department of Molecular Imaging and Therapy, Beckman Research Institute of the City of Hope, Duarte, California
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Jedd D. Wolchok
5Department of Medicine, Weill Cornell Medical College, New York, New York
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  • FIGURE 1.
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    FIGURE 1.

    Biodistribution: Whole-body images of 1 patient at various times after injection of 89Zr-IAB22M2C (1.5-mg minibody dose). All images show most intense activity within spleen, followed by marrow, liver, and kidneys.

  • FIGURE 2.
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    FIGURE 2.

    Biodistribution and normal-organ uptake in 6 patients at 2–4 h (A), 24 h (B), and 92–148 h (C) after injection of 89Zr-IAB22M2C (0.2- to 10.0-mg minibody dose).

  • FIGURE 3.
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    FIGURE 3.

    Serum (A) and whole-body clearance (B) of 89Zr-IAB22M2C at various mass levels, in aggregate mean values of decay-corrected activity retention. %ID = percentage injected dose; WB = whole body.

  • FIGURE 4.
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    FIGURE 4.

    Normal-organ uptake (mean SUVLBM) in spleen (A), marrow (B), liver (C), nodes (D), and muscle (background uptake) (E) vs. minibody mass. BM = bone marrow.

  • FIGURE 5.
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    FIGURE 5.

    A 24-h whole-body (maximum-intensity projection) image in patient imaged with 0.2 mg of 89Zr-IAB22M2C. (A) Intense uptake is noted in lymph nodes. (B and C) Fusion image at 24 h shows 89Zr-IAB22M2C uptake in lesion in deltoid (B), which was also 18F-FDG–positive (C). (D) Hematoxylin- and eosin-stained section shows melanoma tumor nodules on right within skeletal muscle. (E) Immunohistochemistry highlights presence of CD8+ T cells at periphery and infiltrating tumor.

  • FIGURE 6.
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    FIGURE 6.

    Whole-body (maximum-intensity projection) image (left) and 89Zr-IAB22M2C (0.5 mg) images (right) of patient with hepatocellular carcinoma. 89Zr-IAB22M2C–positive lesions are seen in 2 liver metastases (SUVmax, 14.6 and 22.85), and additional uptake is seen in 3 abdominal lymph node metastases (SUVmax, 5.85–10.9).

  • FIGURE 7.
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    FIGURE 7.

    Whole-body (maximum-intensity projection) image (A), 89Zr-IAB22M2C (1.0 mg) images (B), and 18F-FDG images (C) of patient with lung cancer not initiated on immunotherapy. Lesions that are 18F-FDG–positive in left neck (SUVmax, 17.8; 3.2 cm), mediastinum (SUVmax, 11.1; 2.2 cm), left upper lobe (SUVmax, 20.4; 4.7 cm), and liver (SUVmax, 11.6; 3.7 cm) show no uptake of 89Zr-IAB22M2C.

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    TABLE 1

    Patient Demographics

    DemographicData
    Total patients (n)6
    Age range (y)38–81
    Sex (n)
     Male3
     Female3
    Primary malignancy (n)
     Melanoma1
     Hepatocellular carcinoma1
     Lung4
    Treatment profile for current immunotherapy (n)
     None1
     Current < 1 mo from imaging1
     Current > 6 mo from imaging2
     Prior > 6 mo from imaging2

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Journal of Nuclear Medicine: 61 (4)
Journal of Nuclear Medicine
Vol. 61, Issue 4
April 1, 2020
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First-in-Humans Imaging with 89Zr-Df-IAB22M2C Anti-CD8 Minibody in Patients with Solid Malignancies: Preliminary Pharmacokinetics, Biodistribution, and Lesion Targeting
Neeta Pandit-Taskar, Michael A. Postow, Matthew D. Hellmann, James J. Harding, Christopher A. Barker, Joseph A. O’Donoghue, Martha Ziolkowska, Shutian Ruan, Serge K. Lyashchenko, Frank Tsai, Michael Farwell, Tara C. Mitchell, Ron Korn, William Le, Jason S. Lewis, Wolfgang A. Weber, Deepak Behera, Ian Wilson, Michael Gordon, Anna M. Wu, Jedd D. Wolchok
Journal of Nuclear Medicine Apr 2020, 61 (4) 512-519; DOI: 10.2967/jnumed.119.229781

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First-in-Humans Imaging with 89Zr-Df-IAB22M2C Anti-CD8 Minibody in Patients with Solid Malignancies: Preliminary Pharmacokinetics, Biodistribution, and Lesion Targeting
Neeta Pandit-Taskar, Michael A. Postow, Matthew D. Hellmann, James J. Harding, Christopher A. Barker, Joseph A. O’Donoghue, Martha Ziolkowska, Shutian Ruan, Serge K. Lyashchenko, Frank Tsai, Michael Farwell, Tara C. Mitchell, Ron Korn, William Le, Jason S. Lewis, Wolfgang A. Weber, Deepak Behera, Ian Wilson, Michael Gordon, Anna M. Wu, Jedd D. Wolchok
Journal of Nuclear Medicine Apr 2020, 61 (4) 512-519; DOI: 10.2967/jnumed.119.229781
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Keywords

  • 89Zr-IAB22M2C PET
  • minibody
  • CD8+ T cell
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