Assessing PD-L1 expression in Non-Small Cell Lung Cancer patients using68Ga-Labeled Anti-Programmed Death Ligand-1 (PD-L1) Single-Domain Antibody PET/CT

Introduction: The recent rise of checkpoint inhibitor therapy, predominantly programmed cell death 1 (PD-1)/programmed death ligand-1 (PD-L1) antibodies as a standard care of treatment in non-small cell lung cancer (NSCLC) amplifies the importance of a diagnostic tool for the assessment of PD-L1 expression. A nuclear medicine scan that is non-invasive, safe and can give PD-L1 expression information of the whole body including expression in distant metastatic malignancies would have invaluable contributions to patient management. We aimed to assess the safety and imaging characteristics of this radiopharmaceutical in terms of image attribute and uptake in primary and metastatic lesions.

Methods: Four patients (mean age, 65 y; 3 male) with advanced stage non-small cell lung cancer were recruited to a first in human study using 68Ga-Labeled Anti-PD-L1 Single-Domain Antibody (NM-01). A 68Ge/68Ga generator (ITG) was eluted with 0.05M HCl. pH of the eluate was adjusted to 4-5 with 1M sodium acetate and an aliquot was added to a vial containing NODA-GA-NM-01 in PBS. 68Ga-NODA-GA-NM-01 was obtained after a 10-minute incubation at room temperature (pH 4-5). The product was diluted in saline, radiochemical purity was determined by ITLC (ITLC-SG/citrate buffer pH 5.4). No purification was necessary. Administered activity was 1.5-2.2 MBq/kg, corresponding to 150-175 μg of NM-01. Patients were scanned at 30 minutes, 1 hour and 2 hour time points post injection. Scans were visually analyzed and level of uptake in each lesion was quantified using standardized uptake values maximum (SUVmax).

Results: Heterogenous radiotracer uptake patterns were observed in all four patients primary tumour and metastatic lesions, comparable to findings reported in our ^99mTc-labeled-anti-PD-L1 SPECT/CT study. SUVmax of each primary tumour uptake were in the range of 2.3 -3.7 SUVmax, whilst nodal metastases portrayed higher uptake ranging from 2.9- 7.2 SUVmax. Heterogeneity was observed within the primary tumour with differences in radiotracer uptake areas that had little to no uptake. Radiotracer uptake was observed in distant metastases including in soft tissue mass in occipital region with 4.1 SUVmax. No drug-related adverse events occurred in this study. Tracer biodistribution was observed in the kidneys, spleen and liver. Conclusion: This ongoing first in human study has demonstrated that 68Ga-Labeled Anti-PD-L1 Single-Domain Antibody PET/CT is safe and showed good tumour uptake with low lung background suggestive of its clinical utility in assessing PD-L1 expression in non-small cell lung cancer. Further information is to be acquired to make histopathological correlation and to establish statistical significance.