Imaging alloreactive T cells provides early warning of organ transplant rejection

Diagnosis of organ transplant rejection relies upon biopsy approaches to confirm alloreactive T cell infiltration in the graft. Immune molecular monitoring is under investigation to screen for rejection, though these techniques have suffered from low specificity and lack of spatial information. ImmunoPET utilizing antibodies conjugated to radioisotopes has the potential to improve early and accurate detection of graft rejection. ImmunoPET is capable of noninvasively visualizing the dynamic distribution of cells expressing specific immune markers in the entire body over time. In this work, we identify and characterize OX40 as a surrogate biomarker for alloreactive T cells in organ transplant rejection and monitor its expression by utilizing immunoPET. In a dual murine heart transplant model that has both syngeneic and allogeneic hearts engrafted in bilateral ear pinna on the recipients, OX40 immunoPET clearly depicted alloreactive T cells in the allograft and draining lymph node that were not observed in their respective isograft counterparts. OX40 immunoPET signals also reflected the subject's immunosuppression level with tacrolimus in this study. OX40 immunoPET is a promising approach that may bridge molecular monitoring and morphological assessment for improved transplant rejection diagnosis

Visualization of activated T cells by OX40-immunoPET as a strategy for diagnosis of acute Graft-versus-Host-Disease

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