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PET/CT Imaging of
- Source :
- Molecular Imaging and Biology
- Publication Year :
- 2020
-
Abstract
- Purpose Programmed cell death-1 receptor (PD-1) and its ligand (PD-L1) are the targets for immunotherapy in many cancer types. Although PD-1 blockade has therapeutic effects, the efficacy differs between patients. Factors contributing to this variability are PD-L1 expression levels and immune cells present in tumors. However, it is not well understood how PD-1 expression in the tumor microenvironment impacts immunotherapy response. Thus, imaging of PD-1-expressing immune cells is of interest. This study aims to evaluate the biodistribution of Zirconium-89 (89Zr)-labeled pembrolizumab, a humanized IgG4 kappa monoclonal antibody targeting PD-1, in healthy cynomolgus monkeys as a translational model of tracking PD-1-positive immune cells. Procedures Pembrolizumab was conjugated with the tetrafluorophenol-N-succinyl desferal-Fe(III) ester (TFP-N-sucDf) and subsequently radiolabeled with 89Zr. Four cynomolgus monkeys with no previous exposure to humanized monoclonal antibodies received tracer only or tracer co-injected with pembrolizumab intravenously over 5 min. Thereafter, a static whole-body positron emission tomography (PET) scan was acquired with 10 min per bed position on days 0, 2, 5, and 7. Image-derived standardized uptake values (SUVmean) were quantified by region of interest (ROI) analysis. Results 89Zr-N-sucDf-pembrolizumab was synthesized with high radiochemical purity (> 99 %) and acceptable molar activity (> 7 MBq/nmol). In animals dosed with tracer only, 89Zr-N-sucDf-pembrolizumab distribution in lymphoid tissues such as mesenteric lymph nodes, spleen, and tonsils increased over time. Except for the liver, low radiotracer distribution was observed in all non-lymphoid tissue including the lung, muscle, brain, heart, and kidney. When a large excess of pembrolizumab was co-administered with a radiotracer, accumulation in the lymph nodes, spleen, and tonsils was reduced, suggestive of target-mediated accumulation. Conclusions 89Zr-N-sucDf-pembrolizumab shows preferential uptake in the lymphoid tissues including the lymph nodes, spleen, and tonsils. 89Zr-N-sucDf-pembrolizumab may be useful in tracking the distribution of a subset of immune cells in non-human primates and humans. Trial Registration ClinicalTrials.gov Identifier: NCT02760225 Supplementary Information The online version contains supplementary material available at 10.1007/s11307-020-01558-w.
- Subjects :
- Male
Radioisotopes
PD-1-positive immune cells
Spleen and tonsils
Programmed Cell Death 1 Receptor
Cynomolgus monkeys
Standardized uptake values (SUVmean)
Antibodies, Monoclonal, Humanized
Molecular Imaging
Macaca fascicularis
Antineoplastic Agents, Immunological
Neoplasms
Positron Emission Tomography Computed Tomography
Models, Animal
89Zr-N-sucDf-pembrolizumab
Animals
Female
Tissue Distribution
Immunotherapy
Zirconium
Mesenteric lymph nodes
Positron emission tomography (PET) imaging
Research Article
Subjects
Details
- ISSN :
- 18602002
- Volume :
- 23
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Molecular imaging and biology
- Accession number :
- edsair.pmid..........d8db8b78a03a9404b4b89044a2035502