| Literature DB >> 28572504 |
John A Ronald1,2,3,4, Byung-Su Kim5, Gayatri Gowrishankar1,2, Mohammad Namavari1,2, Israt S Alam1,2, Aloma D'Souza1,2, Hidekazu Nishikii5, Hui-Yen Chuang1,6, Ohad Ilovich1,2, Chih-Feng Lin1,7,8, Robert Reeves1,2, Adam Shuhendler1,2, Aileen Hoehne1,2, Carmel T Chan1,2, Jeanette Baker5, Shahriar S Yaghoubi9, Henry F VanBrocklin10, Randall Hawkins10, Benjamin L Franc10, Salma Jivan10, James B Slater10, Emily F Verdin10, Kenneth T Gao10, Jonathan Benjamin5, Robert Negrin5, Sanjiv Sam Gambhir11,2.
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. ©2017 American Association for Cancer Research.Entities:
Mesh:
Year: 2017 PMID: 28572504 PMCID: PMC5505323 DOI: 10.1158/0008-5472.CAN-16-2953
Source DB: PubMed Journal: Cancer Res ISSN: 0008-5472 Impact factor: 12.701