التفاصيل البيبلوغرافية
| العنوان: |
Noninvasive Imaging of Tumor PD-L1 Expression Using [ 99m Tc]Tc-Labeled KN035 with SPECT/CT |
| المؤلفون: |
Yingying Zhang (42910), Ying Ding (152708), Ning Li (45258), Sen Wang (135167), Si Zhou (669724), Ruping Li (5829428), Hui Yang (91136), Wenliang Li (187808), Jinrong Qu (2523172) |
| سنة النشر: |
2022 |
| مصطلحات موضوعية: |
Biophysics, Medicine, Cell Biology, Genetics, Physiology, Immunology, Cancer, Space Science, Chemical Sciences not elsewhere classified, invasive tissue collection, identifying patients likely, 59 ± 0, 54 ± 0, 40 ± 0, 99m (< sup, 24 h post, therapy remains challenging, 68 ± 0, l1 status throughout, 99m , ), mild tumor uptake, high specific affinity, 4 h post, l1 expression heterogeneity, 31 ± 2, noninvasive spect imaging, ct imaging showed, noninvasive imaging, ct imaging |
| الوصف: |
Programmed cell death protein-1/ligand-1 (PD-1/PD-L1) checkpoint blockade is a major breakthrough in cancer therapy, but identifying patients likely to benefit from this therapy remains challenging. Immunohistochemistry is not informative about PD-L1 expression heterogeneity because of the limitations of invasive tissue collection. Noninvasive SPECT imaging is an approach to patient selection and therapeutic monitoring by assessing the PD-L1 status throughout the whole body. Here, we radiolabeled a single-domain PD-L1 antibody with technetium-99m ( 99m Tc) for immune-SPECT imaging to evaluate its feasibility of detecting PD-L1 expression. The radiochemical purity of [ 99m Tc]Tc-HYNIC-KN035 was 99.40 ± 0.11% with a specific activity of 2.68 MBq/μg. [ 99m Tc]Tc-HYNIC-KN035 displayed a high PD-L1 specificity both in vitro and in vivo and showed a high specific affinity for PD-L1 with an equilibrium dissociation constant ( K D ) of 31.04 nM. The binding of [ 99m Tc]Tc-HYNIC-KN035 to H1975 cells (high expression of PD-L1) was much higher than to A549 cells (low expression of PD-L1). SPECT/CT imaging showed that H1975 tumors were visualized at 4 h post-injection and became clearer with time. However, mild tumor uptake was observed in A549 tumors and H1975 tumors of the blocking group at all time points. The uptake value of [ 99m Tc]Tc-HYNIC-KN035 in H1975 tumors was increased continuously from 9.68 ± 0.91% ID/g at 4 h to 13.31 ± 2.23% ID/g at 24 h post-injection, which was higher than in A549 tumors with %ID/g of 4.59 ± 0.76 and 5.54 ± 0.28 at 4 and 24 h post-injection, respectively. These specific bindings were confirmed by blocking studies. [ 99m Tc]Tc-HYNIC-KN035 can be synthesized easily and specifically targeted to PD-L1 in the tumor environment, allowing PD-L1 expression assessment noninvasively and dynamically with SPECT/CT imaging. |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
unknown |
| العلاقة: |
https://figshare.com/articles/journal_contribution/Noninvasive_Imaging_of_Tumor_PD-L1_Expression_Using_sup_99m_sup_Tc_Tc-Labeled_KN035_with_SPECT_CT/21763640Test |
| DOI: |
10.1021/acs.molpharmaceut.2c00874.s001 |
| الإتاحة: |
https://doi.org/10.1021/acs.molpharmaceut.2c00874.s001Test |
| حقوق: |
CC BY-NC 4.0 |
| رقم الانضمام: |
edsbas.E762FAF1 |
| قاعدة البيانات: |
BASE |
