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

• Published in: Cancer research (Chicago, Ill.) Ill.), 2017-06, Vol.77 (11), p.2893-2902
• Main Authors: Ronald, John A, Kim, Byung-Su, Gowrishankar, Gayatri, Namavari, Mohammad, Alam, Israt S, D'Souza, Aloma, Nishikii, Hidekazu, Chuang, Hui-Yen, Ilovich, Ohad, Lin, Chih-Feng, Reeves, Robert, Shuhendler, Adam, Hoehne, Aileen, Chan, Carmel T, Baker, Jeanette, Yaghoubi, Shahriar S, VanBrocklin, Henry F, Hawkins, Randall, Franc, Benjamin L, Jivan, Salma, Slater, James B, Verdin, Emily F, Gao, Kenneth T, Benjamin, Jonathan, Negrin, Robert, Gambhir, Sanjiv Sam
• Format: Article
• Language: English
• Subjects: Acute Disease; Adult; Animals; Cancer; Cell Line, Tumor; Diagnosis; Female; Graft vs Host Disease - genetics; Graft-versus-host reaction; Grafting; Hematopoietic Stem Cell Transplantation - methods; Humans; Immunotherapy; Invasiveness; Kinetics; Leukemia; Lymphocytes; Lymphocytes T; Medical treatment; Mice; Mice, Inbred BALB C; Middle Aged; Organs; Positron-Emission Tomography - methods; Salvage; Side effects; Stem cell transplantation; T-Lymphocytes - immunology; T-Lymphocytes - pathology; Tissues; Transplantation; Transplantation Conditioning - methods; Transplantation, Homologous - methods; Transplants & implants; Young Adult
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-16-2953

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. .