Using dynamic whole-body positron emission tomography (PET), a group of scientists at the University of California, Davis, has imaged for the first time the immune response of recovering patients infected with the COVID-19 virus. Their study, published in Science Advances, could help lead to a better understanding of how the body’s immune system responds to viral infections and the development of long-term protection against reinfection.
The researchers used the uEXPLORER whole-body PET scanner. This is an innovative imaging technology developed at UC Davis in collaboration with United Imaging Healthcare.
Dynamic positron emission computed tomography involves injecting a very small amount of a radioactive tracer into the patient’s body and then performing continuous imaging over a period of time. Dynamic Positron Emission Computed Tomography (PET) is an innovative technique that involves injecting a radiotracer into a patient’s body and then continuously imaging the patient over a period of time, essentially creating a movie showing the kinetics (distribution over time) of the radiotracer in the body. Mathematical models can then be applied to extract biologically relevant information.
Whole-body PET scanners allow simultaneous dynamic imaging and kinetic modeling of all organs in the body. They are significantly more sensitive than conventional PET systems. This means better image quality and the ability to use lower doses of radiotracer.
“Dynamic whole-body positron emission computed tomography is currently the only technology with an acceptable radiation dose to non-invasively quantify the distribution and transport (movement) of immune cells in all tissues of the living human body,” said Negar Omidvari, first author and assistant project scientist in the Department of Biomedical Engineering at the University of California, Davis.
A non-invasive technique for studying the human immune response
CD8+ T cells are specific immune cells that contain CD8 protein on their surface. During a viral infection, naïve (non-customized) CD8+ T cells are activated and become cytotoxic. This means that they find and kill infected cells. Some of these CD8+ cells develop into antigen-specific memory T cells, which are used for long-term memory protection against reinfection.
These cells circulate in the bloodstream, but are primarily found and function in non-blood tissues, especially lymphoid organs such as bone marrow, spleen, tonsils and lymph nodes.
“There is increasing interest in studying the critical role of CD8 + T cells in immune response and memory. However, assessing immunological changes in non-blood tissues is challenging due to the invasive nature of biopsies. In some cases, it is impractical to assess even in certain anatomical regions of the living participant, such as the brain, spinal cord, cardiopulmonary tissues, and vascular tissues,” Omidwari said.” The challenge, therefore, was to find a non-invasive, quantitative method to measure the distribution and transport of CD8+ T cells in vivo that could also be used safely in healthy populations.
Results of the study
In this study, researchers recruited three healthy people and five patients who had recovered from COVID-19 infection. The recovered patients had mild or moderate symptoms and were not hospitalized.
The research team injected the participants with a small amount of radioactive fluid, which included an immune PET radiotracer (8Zr-Df-Crefmirlimab) targeting human CD89. Ninety hours after the injection, the team performed a 60-minute dynamic scan, a 60-minute scan, and a 48-hour <> minute scan on each participant. Four months later, the recovered patients received the same scans.
The researchers measured the activity of the radiotracer in blood and non-blood tissues using PET images. They performed kinetic modeling to isolate the effects of blood circulation on the tissues. In this way, they were able to measure tissue uptake of the radiotracer independent of imaging time and differences in each participant’s blood.
Key findings
The researchers used whole-body positron emission computed tomography to noninvasively measure the distribution of T-cells in all tissue types throughout the body and obtained excellent image quality. The study showed high uptake of CD8 + T cells in the lymphoid organs of all participants. Spleen
