PT  - JOURNAL ARTICLE
AU  - Gaochao Lv
AU  - Xiaorong Sun
AU  - Ling Qiu
AU  - Yan Sun
AU  - Ke Li
AU  - Qingzhu Liu
AU  - Qi Zhao
AU  - Songbing Qin
AU  - Jianguo Lin
TI  - PET Imaging of Tumor PD-L1 Expression with a Highly Specific Nonblocking Single-Domain Antibody
AID  - 10.2967/jnumed.119.226712
DP  - 2020 Jan 01
TA  - Journal of Nuclear Medicine
PG  - 117--122
VI  - 61
IP  - 1
4099  - http://jnm.snmjournals.org/content/61/1/117.short
4100  - http://jnm.snmjournals.org/content/61/1/117.full
SO  - J Nucl Med2020 Jan 01; 61
AB  - Although immunotherapy through programmed death 1/programmed death ligand 1 (PD-1/PD-L1) checkpoint blockade has shown impressive clinical outcomes, not all patients respond to it. Recent studies have demonstrated that the expression level of PD-L1 in tumors is one of the factors that correlate with PD-1/PD-L1 checkpoint blockade therapy. Herein, a 68Ga-labeled single-domain antibody tracer, 68Ga-NOTA-Nb109, was designed and developed for specific and noninvasive imaging of PD-L1 expression in a melanoma-bearing mouse model. Methods: The single-domain antibody Nb109 was labeled with the radionuclide 68Ga through a NOTA chelator. An in vitro binding assay was performed to assess the affinity and binding epitope of Nb109 to PD-L1. The clinical application value of 68Ga-NOTA-Nb109 was evaluated by a stability assay; by biodistribution and pharmacokinetics studies; and by PET imaging, autoradiography, and immunohistochemical staining studies on tumor-bearing models with differences in PD-L1 expression. Results: 68Ga-NOTA-Nb109 was obtained with a radiochemical yield of more than 95% and radiochemical purity of more than 98% in 10 min. It showed a highly specific affinity for PD-L1, with an equilibrium dissociation constant of 2.9 × 10−9 M. A competitive binding assay indicated Nb109 to have a binding epitope different from that of PD-1 and PD-L1 antibody. All biodistribution, PET imaging, autoradiography, and immunohistochemical staining studies revealed that 68Ga-NOTA-Nb109 specifically accumulated in A375-hPD-L1 tumor, with a maximum uptake of 5.0% ± 0.35% injected dose/g at 1 h. Conclusion: 68Ga-NOTA-Nb109 holds great potential for noninvasive PET imaging of the PD-L1 status in tumors and for timely evaluation of the effect of immune checkpoint targeting treatment.