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• W4313455110 abstract "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 (99mTc) for immune-SPECT imaging to evaluate its feasibility of detecting PD-L1 expression. The radiochemical purity of [99mTc]Tc-HYNIC-KN035 was 99.40 ± 0.11% with a specific activity of 2.68 MBq/μg. [99mTc]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 (KD) of 31.04 nM. The binding of [99mTc]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 [99mTc]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. [99mTc]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." @default.
• W4313455110 created "2023-01-06" @default.
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• W4313455110 date "2022-12-21" @default.
• W4313455110 modified "2023-10-16" @default.
• W4313455110 title "Noninvasive Imaging of Tumor PD-L1 Expression Using [^99mTc]Tc-Labeled KN035 with SPECT/CT" @default.
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• W4313455110 doi "https://doi.org/10.1021/acs.molpharmaceut.2c00874" @default.
• W4313455110 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36541699" @default.
• W4313455110 hasPublicationYear "2022" @default.
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