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Meeting ReportOral - PhysicianPharm

89Zr Labeled Anti-PD-1 Antibody PET Monitors phorbol-12-Myristate-13-Acetate (PMA) induced Modulation of Lymphoma PD-1 Expression.

Kyung-Ho Jung, Jin Hee Lee, Mina Kim, Young Seok Cho and KYUNG-HAN LEE
Journal of Nuclear Medicine May 2021, 62 (supplement 1) 64;
Kyung-Ho Jung
1Department of Nuclear Medicine, Samsung Medical Center Seoul Korea, Republic of
2Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University School of Medicine Seoul Korea, Republic of
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Jin Hee Lee
2Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University School of Medicine Seoul Korea, Republic of
1Department of Nuclear Medicine, Samsung Medical Center Seoul Korea, Republic of
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Mina Kim
2Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University School of Medicine Seoul Korea, Republic of
1Department of Nuclear Medicine, Samsung Medical Center Seoul Korea, Republic of
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Young Seok Cho
1Department of Nuclear Medicine, Samsung Medical Center Seoul Korea, Republic of
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KYUNG-HAN LEE
2Samsung Advanced Institute for Health Sciences & Technology, Sungkyunkwan University School of Medicine Seoul Korea, Republic of
1Department of Nuclear Medicine, Samsung Medical Center Seoul Korea, Republic of
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Abstract

64

Introduction: Blockade targeting of the programmed death 1 receptor (PD-1) immune checkpoint is demonstrating remarkable clinical efficacy in the treatment of relapsed and refractory lymphomas. However, selection of patients for this treatment requires predictive biomarkers of response that is not sufficiently provided by immunohistochemistry. We developed an 89Zr-labeled anti-PD-1 immune PET that can noninvasively monitor modulation of PD-1 expression in lymphomas.

Methods: Anti-PD-1 underwent sulfohydryl moiety-specific conjugation with maleimide-deferoxamine followed by 89Zr labeling. Murine T-cell lymphoma EL4 cells underwent binding assays and Western blotting. In vivo pharmacokinetics, biodistribution, and PET imaging were evaluated in mice.

Results: 89Zr-anti-PD-1 synthesis was efficient (radiolabel yield > 70%) and polyacrylamide gel electrophoresis displayed a clear radioactive band at 170 KDa. Instant thin-layer chromatography showed that the radiolabel was stable and > 55% intact after 6 days incubation in 50% FBS. EL4 lymphoma cells expressed PD-1 protein and avidly took up 89Zr-anti-PD-1. Treatment of the cells with 50 ng/ml PMA for 24 h augmented PD-1 expression to 5.8 ± 2.5-fold of controls and increased 89Zr-anti-PD-1 binding to 3.0 ± 0.1-fold. Excellent target specificity was confirmed by a near-complete reduction of binding by excess cold antibody. Intravenous 89Zr-anti-PD-1 followed biexponential blood clearance in mice. PET/CT demonstrated high contrast EL4 lymphoma imaging that was further enhanced following PMA treatment and suppressed by cold antibody. Biodistribution revealed that PMA treatment substantially increased EL4 tumor uptake from 6.6% ± 1.6% to 13.9% ± 3.6% injected dose per gram. Immunoblots confirmed that this correlated with significant increases of tumor PD-1 protein.

Conclusions: 89Zr-anti-PD-1 showed specific targeting with favorable imaging properties. PMA stimulation upregulated PD-1 expression and 89Zr-anti-PD-1 binding to EL4 lymphoma cells in vitro and EL4 tumors in vivo. 89Zr-anti-PD-1 PET can thus be useful for monitoring PD-1 modulation in lymphomas of living subjects.

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Journal of Nuclear Medicine
Vol. 62, Issue supplement 1
May 1, 2021
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89Zr Labeled Anti-PD-1 Antibody PET Monitors phorbol-12-Myristate-13-Acetate (PMA) induced Modulation of Lymphoma PD-1 Expression.
Kyung-Ho Jung, Jin Hee Lee, Mina Kim, Young Seok Cho, KYUNG-HAN LEE
Journal of Nuclear Medicine May 2021, 62 (supplement 1) 64;

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89Zr Labeled Anti-PD-1 Antibody PET Monitors phorbol-12-Myristate-13-Acetate (PMA) induced Modulation of Lymphoma PD-1 Expression.
Kyung-Ho Jung, Jin Hee Lee, Mina Kim, Young Seok Cho, KYUNG-HAN LEE
Journal of Nuclear Medicine May 2021, 62 (supplement 1) 64;
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