Academic Journal
89Zr Immuno-PET Imaging of Tumor PD-1 Reveals That PMA Upregulates Lymphoma PD-1 through NFκB and JNK Signaling
| العنوان: | 89Zr Immuno-PET Imaging of Tumor PD-1 Reveals That PMA Upregulates Lymphoma PD-1 through NFκB and JNK Signaling |
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| المؤلفون: | Kyung-Ho Jung, Jin Hee Lee, Mina Kim, Young Seok Cho, Kyung-Han Lee |
| المصدر: | Molecular Imaging, Vol 2022 (2022) |
| بيانات النشر: | SAGE Publishing, 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Biology (General) LCC:Medical technology |
| مصطلحات موضوعية: | Biology (General), QH301-705.5, Medical technology, R855-855.5 |
| الوصف: | Immune therapy of T-cell lymphoma requires assessment of tumor-expressed programmed cell death protein-1 (PD-1). Herein, we developed an immuno-PET technique that quantitatively images and monitors regulation of PD-1 expression on T-cell lymphomas. Methods. Anti-PD-1 IgG underwent sulfhydryl moiety-specific conjugation with maleimide-deferoxamine and 89Zr labeling. Binding assays and Western blotting were performed in EL4 murine T-cell lymphoma cells. In vivo pharmacokinetics, biodistribution, and PET were performed in mice. Results. 89Zr-PD-1 IgG binding to EL4 cells was completely blocked by cold antibodies, confirming excellent target specificity. Following intravenous injection into mice, 89Zr-PD-1 IgG showed biexponential blood clearance and relatively low normal organ uptake after five days. PET/CT and biodistribution demonstrated high EL4 tumor uptake that was suppressed by cold antibodies. In EL4 cells, phorbol 12-myristate 13-acetate (PMA) increased 89Zr-PD-1 IgG binding (305.5±30.6%) and dose-dependent augmentation of PD-1 expression (15.8±3.8−fold of controls by 200 ng/ml). FACS showed strong PD-1 expression on all EL4 cells and positive but weaker expression on 41.6±2.1% of the mouse spleen lymphocytes. PMA stimulation led to 2.7±0.3-fold increase in the proportion of the strongest PD-1 expressing EL4 cells but failed to influence that of PD-1+ mouse lymphocytes. In mice, PMA treatment increased 89Zr-PD-1 IgG uptake in EL4 lymphomas from 6.6±1.6 to 13.9±3.6%ID/g (P=0.01), and tumor uptake closely correlated with PD-1 level (r=0.771, P |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1536-0121 |
| Relation: | https://doaj.org/toc/1536-0121 |
| DOI: | 10.1155/2022/5916692 |
| URL الوصول: | https://doaj.org/article/52dad9eeaddd4771a1f0c9028aaf5b85 |
| رقم الانضمام: | edsdoj.52dad9eeaddd4771a1f0c9028aaf5b85 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15360121 |
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| DOI: | 10.1155/2022/5916692 |