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Abstract

A major barrier to successful use of allogeneic hematopoietic cell transplantation is acute graft-versus-host disease (aGVHD), a devastating condition that arises when donor T cells attack host tissues. With current technologies, aGVHD diagnosis is typically made after end-organ injury and often requires invasive tests and tissue biopsies. This affects patient prognosis as treatments are dramatically less effective at late disease stages. Here, we show that a novel PET radiotracer, 2'-deoxy-2'-[18F]fluoro-9-β-D-arabinofuranosylguanine ([18F]F-AraG), targeted toward two salvage kinase pathways preferentially accumulates in activated primary T cells. [18F]F-AraG PET imaging of a murine aGVHD model enabled visualization of secondary lymphoid organs harboring activated donor T cells prior to clinical symptoms. Tracer biodistribution in healthy humans showed favorable kinetics. This new PET strategy has great potential for early aGVHD diagnosis, enabling timely treatments and improved patient outcomes. [18F]F-AraG may be useful for imaging activated T cells in various biomedical applications.  

Author information​

Ronald JA1,2,3,4, Kim BS5, Gowrishankar G1,2, Namavari M1,2, Alam IS1,2, D'Souza A1,2, Nishikii H5, Chuang HY1,6, Ilovich O1,2, Lin CF1,7,8, Reeves R1,2, Shuhendler A1,2, Hoehne A1,2, Chan CT1,2, Baker J5, Yaghoubi SS9, VanBrocklin HF10, Hawkins R10, Franc BL10, Jivan S10, Slater JB10, Verdin EF10, Gao KT10, Benjamin J5, Negrin R5, Gambhir SS11,2.

1 Molecular Imaging Program at Stanford, Stanford University, Stanford, California.

2 Department of Radiology, Stanford University School of Medicine, Stanford, California.

3 Robarts Research Institute, Department of Medical Biophysics, The University of Western Ontario, London, Ontario, Canada.

4 Lawson Health Research Institute, London, Ontario, Canada.

5 Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University, Stanford, California.

6 Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.

7 Department of Otolaryngology Head and Neck Surgery, National Taiwan University Hospital, Taipei, Taiwan.

8 Graduate Institute of Pathology, National Taiwan University College of Medicine, Taipei, Taiwan.

9 Cellsight Technologies Incorporated, San Francisco, California.

10 Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California.

11 Molecular Imaging Program at Stanford, Stanford University, Stanford, California. sgambhir@stanford.edu.