Visualization of activated T cells by OX40-immunoPET as a strategy for diagnosis of acute Graft-versus-Host-Disease. Cancer research Alam, I. S., Simonetta, F., Scheller, L., Mayer, A. T., Murty, S., Vermesh, O., Nobashi, T. W., Lohmeyer, J. K., Hirai, T., Baker, J., Lau, K. H., Negrin, R., Gambhir, S. S. 2020

Abstract

Graft versus host disease (GvHD) is a major complication of allogeneic hematopoietic cell transplantation (HCT), mediated primarily by donor T cells that become activated and attack host tissues. Non-invasive strategies detecting T cell activation would allow for early diagnosis and possibly more effective management of HCT recipients. Positron emission tomography (PET) imaging is a sensitive and clinically relevant modality ideal for GvHD diagnosis and there is a strong rationale for the use of PET tracers that can monitor T cell activation and expansion with high specificity. The tumor necrosis factor (TNF) receptor superfamily member OX40 (CD134) is a cell surface marker that is highly specific for activated T cells, is upregulated during GvHD, and mediates disease pathogenesis. We recently reported the development of an antibody-based activated T cell imaging agent targeting OX40. In the present study, we visualize the dynamics of OX40 expression in a major histocompatibility complex (MHC)-mismatch mouse model of acute GvHD using OX40-immunoPET. This approach enabled visualization of T cell activation at early stages of disease, prior to overt clinical symptoms with high sensitivity and specificity. This study highlights the potential utility of the OX40 PET imaging as a new strategy for GvHD diagnosis and therapy monitoring.

View details for DOI 10.1158/0008-5472.CAN-20-1149

View details for PubMedID 32900772