ICOS immunoPET enables visualization of activated T cells and early diagnosis of murine acute gastrointestinal GvHD

Zunyu Xiao, Israt S. Alam, Federico Simonetta, Weiyu Chen, Lukas Scheller, Surya Murty, Juliane K. Lohmeyer, Teresa L. Ramos, Michelle L. James, Robert S. Negrin*, Sanjiv S. Gambhir

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

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 tissues, 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 positron emission tomography (PET) (immunoPET) imaging of T-cell activation post–allogeneic HCT is a promising strategy toward 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 Zirconium-89-deferoxamine-ICOS monoclonal antibody 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 Zirconium-89-deferoxamine-ICOS monoclonal antibody 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.

Original languageEnglish
Pages (from-to)4782-4792
Number of pages11
JournalBlood advances
Volume6
Issue number16
DOIs
Publication statusPublished - 23 Aug 2022
Externally publishedYes

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