Journal
CANCER RESEARCH
Volume 77, Issue 11, Pages 2893-2902Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-16-2953
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Funding
- NCI ICMIC [P50CA114747]
- NCI [RO1 R01CA201719]
- Ben & Catherine Ivy Foundation
- Phase II SBIR [HHSN261201300063C]
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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-beta-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. (C) 2017 AACR.
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