RT Journal Article
SR Electronic
T1 First-in-human evaluation of a PD-L1-binding peptide radiotracer in non-small cell lung cancer patients with PET
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP jnumed.121.262045
DO 10.2967/jnumed.121.262045
A1 Xin Zhou
A1 Jinquan Jiang
A1 Xue Yang
A1 Teli Liu
A1 Jin Ding
A1 Sridhar Nimmagadda
A1 Martin G. Pomper
A1 Hua Zhu
A1 Jun Zhao
A1 Zhi Yang, Professor
A1 Nan Li
YR 2021
UL http://jnm.snmjournals.org/content/early/2021/07/29/jnumed.121.262045.abstract
AB Background: 68Ga-NOTA-WL12 is a peptide-based positron emission tomography (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 advanced non-small cell lung cancer (NSCLC) patients. Methods: In vitro assessment of the relationship between PD-L1 expression and cellular uptake of 68Ga-NOTA-WL12 was performed, followed by in vivo evaluation of 68Ga-NOTA-WL12 uptake in animal models. Nine NSCLC patients with positive PD-L1 expression in lesions were enrolled. 68Ga-NOTA-WL12 and paired 18F-FDG PET/CT imaging were performed. The patients were monitored for adverse events. The uptake (SUV/L and kBq/mL) values of tumors and normal organs were obtained. The biodistribution, radiation dosimetry and relationship of tumor uptake and PD-L1 expression were then evaluated. Follow-up 18F-FDG PET/CT was performed in patients who had undergone treatment with a combination of pembrolizumab with chemotherapy. Results: The cellular and animal experiments demonstrated that PD-L1 expression correlated with the uptake of 68Ga-NOTA-WL12, and PD-L1-positive tumors exhibited high uptake of 68Ga-NOTA-WL12. Clinical research showed that 68Ga-NOTA-WL12 PET imaging is safe with acceptable radiation dosimetry. Physiological tracer uptake was mainly visible in the liver, spleen, small intestine and kidney. High contrast of tumors was observed, particularly in the lungs with a T/lung ratio of 4.45 ±1.89 at 1 h. One hour was a suitable timepoint for image acquisition because no significant differences were noted in the tumor-to-background ratios between 1 and 2 h. Additionally, a strong relationship was found between the tumor uptake (SUVpeak) and PD-L1 immunohistochemistry results (r = 0.9349; P = 0.002). 68Ga-NOTA-WL12 uptake before therapy might 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 the tumor PD-L1 expression levels, indicating potential benefits for clinical PD-L1 therapy.