RT Journal Article
SR Electronic
T1 First-in-Humans Evaluation of a PD-L1–Binding Peptide PET Radiotracer in Non–Small Cell Lung Cancer Patients
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 536
OP 542
DO 10.2967/jnumed.121.262045
VO 63
IS 4
A1 Zhou, Xin
A1 Jiang, Jinquan
A1 Yang, Xue
A1 Liu, Teli
A1 Ding, Jin
A1 Nimmagadda, Sridhar
A1 Pomper, Martin G.
A1 Zhu, Hua
A1 Zhao, Jun
A1 Yang, Zhi
A1 Li, Nan
YR 2022
UL http://jnm.snmjournals.org/content/63/4/536.abstract
AB 68Ga-NOTA-WL12 is a peptide-based PET imaging agent. We conducted a first-in-human study of 68Ga-NOTA-WL12 for PET to study the in vivo biodistribution, metabolism, radiation dosimetry, safety, and potential for quantifying programmed death ligand-1 (PD-L1) expression levels in patients with advanced non–small cell lung cancer (NSCLC). Methods: In vitro assessment of the PD-L1 expression and cellular uptake of 68Ga-NOTA-WL12 was performed, followed by in vivo evaluation of 68Ga-NOTA-WL12 uptake in mouse models with tumors. Nine patients with NSCLC with lesions expressing PD-L1 were enrolled and monitored for adverse events during the study. 68Ga-NOTA-WL12 and paired 18F-FDG PET/CT imaging were performed. Uptake (SUV, SUL [SUVlean], and kBq/mL) values of tumors and normal organs were obtained. Radiopharmaceutical biodistribution, radiation dosimetry, and the relationship of tumor uptake to PD-L1 expression were evaluated. Follow-up 18F-FDG PET/CT was performed in patients who had undergone treatment with a combination of pembrolizumab with chemotherapy. Results: 68Ga-NOTA-WL12 exhibited PD-L1–specific uptake in vitro and in PD-L1–positive tumors in vivo. 68Ga-NOTA-WL12 PET imaging proved safe with acceptable radiation dosimetry. Physiologic tracer uptake was mainly visible in the liver, spleen, small intestine, and kidney. Tumors were clearly visible, particularly in the lungs, with a tumor-to-lung ratio of 4.45 ± 1.89 at 1 h. One hour was a suitable time point for image acquisition because no significant differences were noted in tumor-to-background ratios between 1 and 2 h. A strong, positive correlation was found between tumor uptake (SUVpeak) and PD-L1 immunohistochemistry results (r = 0.9349; P = 0.002). 68Ga-NOTA-WL12 and 18F-FDG PET studies suggest that PD-L1 PET before therapy may indicate the therapeutic efficacy of pembrolizumab plus chemotherapy combination treatment. Conclusion: Our first-in-human findings demonstrate the safety and feasibility of 68Ga-NOTA-WL12 for noninvasive, in vivo detection of tumor PD-L1 expression levels, indicating potential benefits for clinical PD-L1 therapy.