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AbstractAbstract
[en] Hematopoietic stem cell transplantation is the only curative treatment for several hematological malignancies and immune deficiency syndromes. Nevertheless, the development of graft-versus-host disease (GvHD) after transplantation is a severe complication with high morbidity and mortality. The aim of this study was to image human T cells during GvHD development and their migration into GvHD-related organs. By using a radiolabeled anti-human CD monoclonal antibody (mAb), we were able to visualize GvHD progression in a humanized mouse model. Human peripheral blood mononuclear cells (PBMC) were transferred into immunodeficient mice (initially n = 11 mice/group) to induce GvHD. One group additionally received regulatory T cells (Treg) for prevention of GvHD. T cell migration was visualized by sequential small animal PET/MRI using Zr-labeled anti-human CD mAb. Flow cytometry and immunohistochemistry were used to measure T cell frequencies in relevant organs at different time points after engraftment. Using radiolabeled anti-CD mAb, we successfully visualized human T cells in inflamed organs of mice by Zr-anti-CD-PET/MRI. Upon GvHD progression, we observed increased numbers of CD T cells in the liver (22.9% on day 3; 94.2% on day 10) and the spleen (4.4% on day 3; 58.8% on day 10) which correlated with clinical symptoms. The liver showed distinct spot-like lesions representing a strong focal accumulation of T cells. Administration of Treg prior GvHD induction reduced T cell accumulation in the liver from 857 ± 177 CD cells/mm to 261 ± 82 CD cells/mm and thus prevented GvHD. Zr-labeled anti-human CD mAb can be used as a proof of concept to detect the exact spatio-temporal distribution of GvHD-mediating T cells. In the future, radiolabeled T cell-specific mAb could be employed as a predictive early biomarker during the course of GvHD maybe even before clinical signs of the disease become evident. Furthermore, monitoring T cell migration and proliferation might improve tailored GvHD therapy.
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Source
Available from: http://dx.doi.org/10.1007/s00259-019-04507-0
Record Type
Journal Article
Journal
European Journal of Nuclear Medicine and Molecular Imaging; ISSN 1619-7070;
; CODEN EJNMA6; v. 47(5); p. 1314-1325

Country of publication
ANIMAL CELLS, ANIMALS, ANTIBODIES, BETA DECAY RADIOISOTOPES, BETA-PLUS DECAY RADIOISOTOPES, BODY, COMPUTERIZED TOMOGRAPHY, DAYS LIVING RADIOISOTOPES, DIAGNOSTIC TECHNIQUES, DIGESTIVE SYSTEM, DISEASES, DRUGS, ELECTRON CAPTURE RADIOISOTOPES, EMISSION COMPUTED TOMOGRAPHY, EVEN-ODD NUCLEI, GLANDS, INTERMEDIATE MASS NUCLEI, ISOMERIC TRANSITION ISOTOPES, ISOTOPES, LABELLED COMPOUNDS, MAMMALS, MATERIALS, MEDICINE, MINUTES LIVING RADIOISOTOPES, NUCLEI, ORGANS, PATHOLOGICAL CHANGES, RADIOACTIVE MATERIALS, RADIOISOTOPES, RODENTS, SOMATIC CELLS, SYMPTOMS, TOMOGRAPHY, TRANSPLANTS, VERTEBRATES, ZIRCONIUM ISOTOPES
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