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Scientific article
Open access
English

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

Published inBlood advances, vol. 6, no. 16, p. 4782-4792
Publication date2022-08-23
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.

eng
Keywords
  • Animals
  • Antibodies, Monoclonal
  • Deferoxamine
  • Early Diagnosis
  • Graft vs Host Disease / diagnostic imaging
  • Inducible T-Cell Co-Stimulator Protein / analysis
  • Mice
  • Positron-Emission Tomography
  • T-Lymphocytes
  • Transplantation, Homologous / adverse effects
Funding
  • NCI NIH HHS - [P01 CA049605]
  • NCI NIH HHS - [P30 CA124435]
  • NCI NIH HHS - [R01 CA201719]
Citation (ISO format)
XIAO, Zunyu et al. ICOS immunoPET enables visualization of activated T cells and early diagnosis of murine acute gastrointestinal GvHD. In: Blood advances, 2022, vol. 6, n° 16, p. 4782–4792. doi: 10.1182/bloodadvances.2022007403
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Article (Published version)
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Identifiers
ISSN of the journal2473-9529
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104downloads

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