Development of a radiolabeled site-specific single-domain antibody positron emission tomography probe for monitoring PD-L1 expression in cancer
- Author:
Yinfei CHEN
1
,
2
;
Shiyu ZHU
;
Jiayu FU
;
Jianguo LIN
;
Yan SUN
;
Gaochao LV
;
Minhao XIE
;
Tao XU
;
Ling QIU
Author Information
1. NHC Key Laboratory of Nuclear Medicine,Jiangsu Key Laboratory of Molecular Nuclear Medicine,Jiangsu Institute of Nuclear Medicine,Wuxi,Jiangsu,214063,China
2. Department of Radiopharmaceuticals,School of Pharmacy,Nanjing Medical University,Nanjing,211166,China
- Keywords:
Single-domain antibody;
Site-specific labeling;
Immuno-PET imaging;
PD-L1
- From:
Journal of Pharmaceutical Analysis
2022;12(6):869-878
- CountryChina
- Language:Chinese
-
Abstract:
Despite advances in immunotherapy for the treatment of cancers,not all patients can benefit from programmed cell death ligand 1(PD-L1)immune checkpoint blockade therapy.Anti-PD-L1 therapeutic effects reportedly correlate with the PD-L1 expression level;hence,accurate detection of PD-L1 expression can guide immunotherapy to achieve better therapeutic effects.Therefore,based on the high affinity antibody Nb109,a new site-specifically radiolabeled tracer,68Ga-NODA-cysteine,aspartic acid,and valine(CDV)-Nb109,was designed and synthesized to accurately monitor PD-L1 expression.The tracer 68Ga-NODA-CDV-Nb109 was obtained using a site-specific conjugation strategy with a radiochemical yield of about 95％and radiochemical purity of 97％.It showed high affinity for PD-L1 with a dissociation constant of 12.34±1.65 nM.Both the cell uptake assay and positron emission tomography(PET)imaging revealed higher tracer uptake in PD-L1-positive A375-hPD-L1 and U87 tumor cells than in PD-L1-negative A375 tumor cells.Meanwhile,dynamic PET imaging of a NC1-H1299 xenograft indicated that doxorubicin could upregulate PD-L1 expression,allowing timely interventional immunotherapy.In conclusion,this tracer could sensitively and dynamically monitor changes in PD-L1 expression levels in different cancers and help screen patients who can benefit from anti-PD-L1 immunotherapy.
