학술논문

First-in-human immunoPET imaging of COVID-19 convalescent patients using dynamic total-body PET and a CD8-targeted minibody
Document Type
article
Source
Science Advances. 9(41)
Subject
Biomedical and Clinical Sciences
Immunology
Biomedical Imaging
Coronaviruses
Clinical Research
Bioengineering
Infectious Diseases
Emerging Infectious Diseases
Good Health and Well Being
Humans
Tissue Distribution
COVID-19
Positron-Emission Tomography
CD8-Positive T-Lymphocytes
Zirconium
Cell Line
Tumor
Language
Abstract
With most of the T cells residing in the tissue, not the blood, developing noninvasive methods for in vivo quantification of their biodistribution and kinetics is important for studying their role in immune response and memory. This study presents the first use of dynamic positron emission tomography (PET) and kinetic modeling for in vivo measurement of CD8+ T cell biodistribution in humans. A 89Zr-labeled CD8-targeted minibody (89Zr-Df-Crefmirlimab) was used with total-body PET in healthy individuals (N = 3) and coronavirus disease 2019 (COVID-19) convalescent patients (N = 5). Kinetic modeling results aligned with T cell-trafficking effects expected in lymphoid organs. Tissue-to-blood ratios from the first 7 hours of imaging were higher in bone marrow of COVID-19 convalescent patients compared to controls, with an increasing trend between 2 and 6 months after infection, consistent with modeled net influx rates and peripheral blood flow cytometry analysis. These results provide a promising platform for using dynamic PET to study the total-body immune response and memory.