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Cancer Res. 2017 Jun 1;77(11):2893-2902. doi: 10.1158/0008-5472.CAN-16-2953.

A PET Imaging Strategy to Visualize Activated T Cells in Acute Graft-versus-Host Disease Elicited by Allogenic Hematopoietic Cell Transplant.

Author information

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.

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. Cancer Res; 77(11); 2893-902. ©2017 AACR.

PMID:
28572504
PMCID:
PMC5505323
DOI:
10.1158/0008-5472.CAN-16-2953
[Indexed for MEDLINE]
Free PMC Article

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