Visualizing dynamic changes in PD-L1 expression in non-small cell lung carcinoma with radiolabeled recombinant human PD-1.
Purpose: Tumor heterogeneity limits the predictive value of PD-L1 expression and influences the outcomes of the immunohistochemical assay for therapy-induced changes in PD-L1 levels. This study aimed to determine the predictive value of PD-L1 for non-small cell lung carcinoma (NSCLC), thereby develo...
| Publicado en: | European Journal of Nuclear Medicine & Molecular Imaging Vol. 49; no. 8; pp. 2735 - 2746 |
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| Autores principales: | , , , , |
| Formato: | Journal Article |
| Publicado: |
Springer Nature
Jul2022
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| Acceso en línea: | Ver este registro en EBSCOhost |
| fields | @attributes: recordID: 1 pdfLink: plink: https://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=157529108&site=ehost-live header: @attributes: shortDbName: ccm uiTerm: 157529108 longDbName: CINAHL Complete uiTag: AN controlInfo: bkinfo: dissinfo: jinfo: jid: 16197070 NPC jtl: European Journal of Nuclear Medicine & Molecular Imaging issn: 16197070 maglogo: N pubinfo: dt: Jul2022 vid: 49 iid: 8 pid: 237 pub: Springer Nature place: New York, New York artinfo: ui: 157529108 154920399 10.1007/s00259-022-05680-5 157529108 ppf: 2735 ppct: 11 formats: fmt: – @attributes: type: T – @attributes: type: P tig: atl: Visualizing dynamic changes in PD-L1 expression in non-small cell lung carcinoma with radiolabeled recombinant human PD-1. aug: au: Luo, Haiming Yang, Changwen Kuang, Dong Shi, Sixiang Chan, Annie W. affil: Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, 430074, Wuhan, China sug: ab: Purpose: Tumor heterogeneity limits the predictive value of PD-L1 expression and influences the outcomes of the immunohistochemical assay for therapy-induced changes in PD-L1 levels. This study aimed to determine the predictive value of PD-L1 for non-small cell lung carcinoma (NSCLC), thereby developing imaging agents to non-invasively image and examine the effect of the therapeutic response to PD-L1 blockade therapy. Methods: A cohort of 102 patients with lung cancer was analyzed, and the prognostic significance of PD-L1 expression level was investigated. Recombinant human PD-1 ECD protein (rhPD1) was expressed, purified, and labeled with 64Cu for the evaluation of PD-L1 status in tumors. Mice subcutaneously bearing PD-L1 high-expressing tumor HCC827 and PD-L1 low-expressing tumor A549 were used to determine tracer-target specificity and examine the effect of therapeutic response to PD-L1 blockade therapy. Results: PD-L1 was proved to be a good prognosis marker for NSCLC, and its expression was correlated with the histology of NSCLC. PET imaging revealed high tumor accumulation of 64Cu-NOTA-rhPD1 in HCC827 tumors (9.0 ± 0.5%ID/g), whereas it was 3.2 ± 0.4%ID/g in A549 tumors at 3 h post-injection. The lower tumor uptake (3.1 ± 0.3%ID/g) of 64Cu-labeled denatured rhPD1 in HCC827 tumors at 3 h post-injection (p < 0.001) demonstrated the target specificity of 64Cu-NOTA-rhPD1. Furthermore, PET showed that 64Cu-NOTA-rhPD1 sensitively monitored treatment-related changes in PD-L1 expression, and seemed to be superior to [18F]FDG. Conclusion: We identified PD-L1 as a good prognosis marker for surgically resected NSCLC and developed the PET tracer 64Cu-NOTA-rhPD1 with high target specificity for PD-L1. pubtype: Academic Journal doctype: Journal Article ougenre: Article language: English refInfo: holdings: @attributes: islocal: N |
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