Deuterium MRI of serine metabolism in mouse models of glioblastoma.

Purpose: Serine is a major source of one-carbon units needed for the synthesis of nucleotides and the production of intramitochondrial nicotinamide adenine dinucleotide phosphate (NADPH), and it plays an important role in cancer cell proliferation. The aim of this study was to develop a deuterium (H) MRS imaging method for imaging tumor serine metabolism.

Methods: Sequential (H) spectra and spectroscopic images were used to monitor the metabolism of [2,3,3-H]serine in patient-derived glioblastoma cells in vitro and in tumors obtained by their orthotopic implantation in mouse brain.

Radiosynthesis of [F]FPenM-C2Am: A PET Imaging Agent for Detecting Cell Death.

Imaging agents capable of detecting the extent, timing, and distribution of tumor cell death following treatment could be used in clinical trials of novel cancer therapies to get an early indication of efficacy and subsequently in the clinic to guide treatment in individual patients. We have shown how the C2A domain of synaptotagmin I, which binds the phosphatidylserine exposed by apoptotic and necrotic cells, can be used to image cell death (Bulat et al., EJNMMI Res 10(1):151, 2020; Neves et al.

Assessment of the sensitivity of H MR spectroscopy measurements of [2,3- H ]fumarate metabolism for detecting tumor cell death.

Imaging the metabolism of [2,3- H ]fumarate to produce malate can be used to detect tumor cell death post-treatment. Here, we assess the sensitivity of the technique for detecting cell death by lowering the concentration of injected [2,3- H ]fumarate and by varying the extent of tumor cell death through changes in drug concentration. Mice were implanted subcutaneously with human triple negative breast cancer cells (MDA-MB-231) and injected with 0.

Preclinical PET Imaging of Tumor Cell Death following Therapy Using Gallium-68-Labeled C2Am.

There is an unmet clinical need for imaging agents capable of detecting early evidence of tumor cell death, since the timing, extent, and distribution of cell death in tumors following treatment can give an indication of treatment outcome. We describe here Ga-labeled C2Am, which is a phosphatidylserine-binding protein, for imaging tumor cell death in vivo using positron emission tomography (PET). A one-pot synthesis of Ga-C2Am (20 min, 25 °C, >95% radiochemical purity) has been developed, using a NODAGA-maleimide chelator.

Imaging Glioblastoma Response to Radiotherapy Using 2H Magnetic Resonance Spectroscopy Measurements of Fumarate Metabolism.

Unlabelled: Early detection of tumor cell death in glioblastoma following treatment with chemoradiation has the potential to distinguish between true disease progression and pseudoprogression. Tumor cell death can be detected noninvasively in vivo by imaging the production of [2,3-2H2]malate from [2,3-2H2]fumarate using 2H magnetic resonance (MR) spectroscopic imaging. We show here that 2H MR spectroscopy and spectroscopic imaging measurements of [2,3-2H2]fumarate metabolism can detect tumor cell death in orthotopically implanted glioblastoma models within 48 hours following the completion of chemoradiation.

Metabolic Glycan Labeling of Cancer Cells Using Variably Acetylated Monosaccharides.

Methylcyclopropene (Cyoc)-tagged tetra-acetylated monosaccharides, and in particular mannosamine derivatives, are promising tools for medical imaging of cancer using metabolic oligosaccharide engineering and the extremely fast inverse electron-demand Diels-Alder bioorthogonal reaction. However, the potential of these monosaccharide derivatives has yet to be fully explored due to their low aqueous solubility. To address this issue, we sought to vary the extent of acetylation of Cyoc-tagged monosaccharides and probe its effect on the extent of glycan labeling in various cancer cell lines.

Deuterium MRSI of tumor cell death in vivo following oral delivery of H-labeled fumarate.

Purpose: There is an unmet clinical need for direct and sensitive methods to detect cell death in vivo, especially with regard to monitoring tumor treatment response. We have shown previously that tumor cell death can be detected in vivo from H MRS and MRSI measurements of increased [2,3- H ]malate production following intravenous injection of [2,3- H ]fumarate. We show here that cell death can be detected with similar sensitivity following oral administration of the H-labeled fumarate.

Monitoring tumor cell death in murine tumor models using deuterium magnetic resonance spectroscopy and spectroscopic imaging.

H magnetic resonance spectroscopic imaging has been shown recently to be a viable technique for metabolic imaging in the clinic. We show here that H MR spectroscopy and spectroscopic imaging measurements of [2,3-H]malate production from [2,3-H]fumarate can be used to detect tumor cell death in vivo via the production of labeled malate. Production of [2,3-H]malate, following injection of [2,3-H]fumarate (1 g/kg) into tumor-bearing mice, was measured in a murine lymphoma (EL4) treated with etoposide, and in human breast (MDA-MB-231) and colorectal (Colo205) xenografts treated with a TRAILR2 agonist, using surface-coil localized H MR spectroscopy at 7 T.

F-C2Am: a targeted imaging agent for detecting tumor cell death in vivo using positron emission tomography.

Introduction: Trialing novel cancer therapies in the clinic would benefit from imaging agents that can detect early evidence of treatment response. The timing, extent and distribution of cell death in tumors following treatment can give an indication of outcome. We describe here an F-labeled derivative of a phosphatidylserine-binding protein, the C2A domain of Synaptotagmin-I (C2Am), for imaging tumor cell death in vivo using PET.

Imaging Glycosylation In Vivo by Metabolic Labeling and Magnetic Resonance Imaging.

Glycosylation is a ubiquitous post-translational modification, present in over 50 % of the proteins in the human genome,1 with important roles in cell-cell communication and migration. Interest in glycome profiling has increased with the realization that glycans can be used as biomarkers of many diseases,2 including cancer.3 We report here the first tomographic imaging of glycosylated tissues in live mice by using metabolic labeling and a gadolinium-based bioorthogonal MRI probe.

Imaging Glycosylation In Vivo by Metabolic Labeling and Magnetic Resonance Imaging.

Glycosylation is a ubiquitous post-translational modification, present in over 50% of the proteins in the human genome, with important roles in cell-cell communication and migration. Interest in glycome profiling has increased with the realization that glycans can be used as biomarkers of many diseases, including cancer. We report here the first tomographic imaging of glycosylated tissues in live mice by using metabolic labeling and a gadolinium-based bioorthogonal MRI probe.