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In vivo positron emission tomography imaging for PD-L1 expression in cancer using aptamer

Authors
 Yun Jung Choi  ;  Jun Young Park  ;  Ye Lim Cho  ;  Ju Ri Chae  ;  Hojin Cho  ;  Won Jun Kang 
Citation
 BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, Vol.620 : 105-112, 2022-09 
Journal Title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
ISSN
 0006-291X 
Issue Date
2022-09
MeSH
Animals ; B7-H1 Antigen* / metabolism ; Cell Line, Tumor ; Gallium Radioisotopes / chemistry ; Mice ; Neoplasms* / diagnostic imaging ; Oligonucleotides ; Positron-Emission Tomography / methods ; Programmed Cell Death 1 Receptor
Keywords
Aptamer ; Cancer ; Positron emission tomography ; Programmed death ligand 1 ; Programmed death-1 receptor
Abstract
The programmed death-1 (PD-1) receptor is an immunosuppressive receptor expressed on activated T-cells that elicits an inhibitory signal upon the engagement of its ligand, which is the programmed death ligand 1 (PD-L1). Recent studies have shown that PD-1/PD-L1 blockade can enhance endogenous antitumor immunity. Thus, the PD-1/PD-L1 axis may be a potential therapeutic target for cancer immunotherapy. Aptamers are oligonucleotides with high specificity and affinity for target molecules and promising candidates for molecular imaging and targeted therapy. 68Ga is an attractive radionuclide that serves as a low-cost alternative to cyclotron-produced positron emission tomography (PET) radionuclides. In this study, we developed a 68Ga-labeled PD-L1 aptamer and investigated its target specificity and utility for in vivo PET scanning. In the first part of our study, we evaluated the binding affinity of three PD-L1 aptamers in PD-L1-positive (H1975 and B16F10) and negative (A549 and HT-29) tumor cells by flow cytometry and confocal microscopy. Optical imaging studies of PD-L1 aptamers were performed in H1975 tumor-bearing mice, and the aptamer with the highest binding affinity to PD-L1 positive tumors was selected. PD-L1 aptamers were radiolabeled with 68Ga. PET was performed for in vivo imaging of the 68Ga-NOTA-PD-L1 aptamer in H1975 tumor-bearing mice (PD-L1-positive cells) and A549 tumor-bearing mice (PD-L1-negative cells). Flow cytometry and confocal microscopy showed that PD-L1 aptamers had strong binding to PD-L1-positive H1975 and B16F10 cells. In contrast, PD-L1-negative A549 and HT-29 cells showed low binding to PD-L1 aptamers. Optical imaging studies of H1975 tumor-bearing mice showed the highest uptake of the 2198-06-07 PD-L1 aptamer. PET of 68Ga-NOTA-PD-L1 aptamers demonstrated increased uptake into PD-L1-positive H1975 tumors compared with PD-L1-negative A549 tumors. We confirmed that 68Ga-NOTA-PD-L1 aptamers facilitated the visualization of PD-L1 expression by in vivo PET scanning. These data suggest that 68Ga-NOTA-PD-L1 aptamers could potentially act as tracers for imaging for PD-L1-positive cancers.
Full Text
https://www.sciencedirect.com/science/article/pii/S0006291X22009135?via%3Dihub
DOI
10.1016/j.bbrc.2022.06.059
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Nuclear Medicine (핵의학교실) > 1. Journal Papers
Yonsei Authors
Kang, Won Jun(강원준) ORCID logo https://orcid.org/0000-0002-2107-8160
Park, Jun Young(박준영) ORCID logo https://orcid.org/0000-0003-3403-2767
Cho, Hojin(조호진) ORCID logo https://orcid.org/0000-0002-8686-172X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/191981
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