Abstract
Purpose: Immunotherapy with checkpoint inhibitor programmed cell death 1 (PD-1)/programmed death ligand (PD-L1) antibodies demonstrates improvements in treatment of advanced non-small cell lung cancer (NSCLC). Treatment stratification depends on immunohistochemical PD-L1 measurement of biopsy material, an invasive method that does not account for spatiotemporal heterogeneity. Using a single domain antibody (sdAb), NM-01, against PD-L1, radiolabeled site-specifically with technetium-99m (99mTc) for single photon emission computed tomography (SPECT) imaging, we aimed to assess the safety, radiation dosimetry and imaging characteristics of this radiopharmaceutical and correlate tumor uptake with PD-L1 immunohistochemistry results. Methods: Sixteen patients (mean age 61.7 years, 11 male) with NSCLC were recruited. Primary tumor PD-L1 expression was measured by immunohistochemistry. NM-01 was radiolabeled with [99mTc(OH2)3(CO)3]+ complex binding to its C-terminal hexahistidine tag. Administered activity was 3.8-10.4 MBq/kg, corresponding to 100 µg or 400 µg of NM-01. Whole body planar and thoracic SPECT/CT scans were performed at 1 and 2h post-injection in all patients and 5 patients had additional imaging at 10mins, 3 and 24h for radiation dosimetry calculations. All patients were monitored for adverse events. Results: No drug-related adverse events occurred in this study. The mean effective dose was 8.84×10-3 ± 9.33×10-4 mSv/MBq (3.59 ± 0.74 mSv per patient). Tracer uptake was observed in the kidneys, spleen, liver and bone marrow. SPECT primary tumor-blood pool ratios (T:BP) varied from 1.24 to 2.3 (mean = 1.79) at 1h and 1.24 to 3.53 (mean = 2.22) at 2h (P = 0.005). 2h primary T:BP ratios correlated with PD-L1 immunohistochemistry results (r=0.68, P = 0.014). 2h T:BP was lower in tumors with ≤1% PD-L1 expression (1.89 vs 2.49, P = 0.048). Nodal and bone metastases showed tracer uptake. Heterogeneity (>20%) between primary tumor and nodal T:BP was present in 4 of 12 patients. Conclusion: This first in human study demonstrates that 99mTc-labeled anti-PD-L1-sdAb SPECT/CT imaging is safe and associated with acceptable dosimetry. Tumor uptake is readily visible against background tissues, particularly at 2h when the T:BP ratio correlates with PD-L1 immunohistochemistry results.
- Molecular Imaging
- Oncology: Lung
- SPECT/CT
- Early Phase I
- Non-small cell lung cancer
- PD-L1
- SPECT/CT
- Single domain antibody (sdAb)
Footnotes
Immediate Open Access: Creative Commons Attribution 4.0 International License (CC BY) allows users to share and adapt with attribution, excluding materials credited to previous publications. License: https://creativecommons.org/licenses/by/4.0/. Details: http://jnm.snmjournals.org/site/misc/permission.xhtml.
- Copyright © 2019 by the Society of Nuclear Medicine and Molecular Imaging, Inc.