Abstract

Allogeneic hematopoietic cell transplantation (HCT) is a well-established and potentially curative treatment for a broad range of hematological diseases, bone marrow failure states and genetic disorders. Acute graft-versus-host-disease (GvHD), mediated by donor T cells attacking host tissue, still represents a major cause of morbidity and mortality following allogeneic HCT. Current approaches to diagnosis of gastrointestinal acute GvHD rely on clinical and pathological criteria that manifest at late stages of disease. New strategies allowing for GvHD prediction and diagnosis, prior to symptom onset, are urgently needed. Noninvasive antibody-based PET (immunoPET) imaging of T cell activation post allogeneic HCT is a promising strategy towards this goal. In this work, we identified Inducible T-cell COStimulator (ICOS) as a potential immunoPET target for imaging activated T cells during GvHD. We demonstrate that the use of the 89Zr-DFO-ICOS monoclonal antibody (mAb) PET tracer, allows in vivo visualization of donor T cell activation in target tissues, namely the intestinal tract, in a murine model of acute GvHD. Importantly, we demonstrate that the 89Zr-DFO-ICOS mAb PET tracer does not affect GvHD pathogenesis or the graft-versus-tumor (GvT) effect of the transplant procedure. Our data identify ICOS immunoPET as a promising strategy for early GvHD diagnosis prior to the appearance of clinical symptoms.

View details for DOI 10.1182/bloodadvances.2022007403

View details for PubMedID 35790103