First-in-human immunoPET imaging of COVID-19 convalescent patients using dynamic total-body PET and a CD8-targeted minibody

Author:

Omidvari Negar1ORCID,Jones Terry2ORCID,Price Pat M.3ORCID,Ferre April L.4ORCID,Lu Jacqueline4,Abdelhafez Yasser G.25ORCID,Sen Fatma2,Cohen Stuart H.6,Schmiedehausen Kristin7,Badawi Ramsey D.12ORCID,Shacklett Barbara L.46ORCID,Wilson Ian7,Cherry Simon R.12ORCID

Affiliation:

1. Department of Biomedical Engineering, University of California Davis, Davis, CA, USA.

2. Department of Radiology, University of California Davis Medical Center, Sacramento, CA, USA.

3. Department of Surgery and Cancer, Imperial College London, London, UK.

4. Department of Medical Microbiology and Immunology, School of Medicine, University of California Davis, Davis, CA, USA.

5. Radiotherapy and Nuclear Medicine Department, South Egypt Cancer Institute, Assiut University, Assiut, Egypt.

6. Division of Infectious Diseases, Department of Internal Medicine, University of California Davis Medical Center, Sacramento, CA, USA.

7. ImaginAb Inc., Inglewood, CA, USA.

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 89 Zr-labeled CD8-targeted minibody ( 89 Zr-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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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