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Abstract #5308

Monitoring in vitro and in vivo cell death using AXR, ADC and hyperpolarized [1,4-13C2]fumarate

Athanasia Kaika1, Luca Nagel1, Ulrike Höckendorf2, Geoffrey J. Topping1, Irina Beer3, Frits H. A. van Heijster1, Philipp J. Jost4,5, Natalia P. Ivleva3, and Franz Schilling1
1School of Medicine, Klinikum rechts der Isar, Department of Nuclear Medicine, Technical University of Munich (TUM), Munich, Germany, 2School of Medicine, Klinikum rechts der Isar, Department of Medicine III, Technical University of Munich (TUM), Munich, Germany, 3Chair of Analytical Chemistry and Water Chemistry, Institute of Water Chemistry, Technical University of Munich (TUM), Garching, Germany, 4Chair of Clinical Division of Oncology Department of Internal Medicine, Medical University of Graz, Graz, Austria, 5Chair of University Palliative Care Unit, Medical University of Graz, Graz, Austria

Synopsis

Keywords: Diffusion/other diffusion imaging techniques, Microstructure, FEXSY, FEXI, exchange, water transmembrane permeability, cell deathFilter exchange spectroscopy (FEXSY) and imaging (FEXI) were used to measure apparent exchange rate (AXR) in acute myeloid leukemia cells undergoing apoptosis, necroptosis, or necrosis. Sensitivity of AXR to membrane permeabilization in vitro, while ADC was stable, were confirmed by Annexin V/PI staining and by scanning electron microscopy of microstructural leaks upon necrosis. AXR of murine EL4 lymphoma showed negative and positive correlation with ADC and malate/fumarate ratio, respectively. Tumor H&E histological analyses show clusters of diffuse necrosis in the solid tumor region, which likely contribute to high AXR and MFR variation while ADC is still low.

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