Visualization of Activated T Cells by OX40-ImmunoPET as a Strategy for Diagnosis of Acute Graft-versus-Host Disease
| Autor: | Tomomi Nobashi, Ophir Vermesh, Juliane K. Lohmeyer, Surya Murty, Kenneth Lau, Lukas Scheller, Robert S. Negrin, Aaron T. Mayer, Federico Simonetta, Jeanette Baker, Sanjiv S. Gambhir, Israt S. Alam, Toshihito Hirai |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cancer Research T-Lymphocytes Cell Graft vs Host Disease Disease Lymphocyte Activation Article Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation immune system diseases Positron Emission Tomography Computed Tomography medicine Animals Receptors OX40/analysis Tissue Distribution CD134 Radiopharmaceuticals/pharmacology Receptor Copper Radioisotopes/pharmacology biology business.industry Antibodies Monoclonal Receptors OX40 Receptors OX40/metabolism Antibodies Monoclonal/pharmacology Imaging agent Transplantation surgical procedures operative 030104 developmental biology medicine.anatomical_structure Copper Radioisotopes Oncology 030220 oncology & carcinogenesis Cancer research biology.protein Graft vs Host Disease/immunology Radiopharmaceuticals Antibody business Positron Emission Tomography Computed Tomography/methods |
| Zdroj: | Cancer Res Cancer Research, Vol. 80, No 21 (2020) pp. 4780-4790 |
| ISSN: | 1538-7445 0008-5472 |
| DOI: | 10.1158/0008-5472.can-20-1149 |
| Popis: | 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. Noninvasive strategies detecting T-cell activation would allow for early diagnosis and possibly more effective management of HCT recipients. 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 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 an 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. Significance: OX40-immunoPET imaging is a promising noninvasive strategy for early detection of GvHD, capable of detecting signs of GvHD pathology even prior to the development of overt clinical symptoms. |
| Databáze: | OpenAIRE |
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