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Radiology. Imaging Cancer Jul 2023Theranostics is the combination of two approaches-diagnostics and therapeutics-applied for decades in cancer imaging using radiopharmaceuticals or paired... (Review)
Review
Theranostics is the combination of two approaches-diagnostics and therapeutics-applied for decades in cancer imaging using radiopharmaceuticals or paired radiopharmaceuticals to image and selectively treat various cancers. The clinical use of theranostics has increased in recent years, with U.S. Food and Drug Administration (FDA) approval of lutetium 177 (Lu) tetraazacyclododecane tetraacetic acid octreotate (DOTATATE) and Lu-prostate-specific membrane antigen vector-based radionuclide therapies. The field of theranostics has imminent potential for emerging clinical applications. This article reviews critical areas of active clinical advancement in theranostics, including forthcoming clinical trials advancing FDA-approved and emerging radiopharmaceuticals, approaches to dosimetry calculations, imaging of different radionuclide therapies, expanded indications for currently used theranostic agents to treat a broader array of cancers, and emerging ideas in the field. Molecular Imaging, Molecular Imaging-Cancer, Molecular Imaging-Clinical Translation, Molecular Imaging-Target Development, PET/CT, SPECT/CT, Radionuclide Therapy, Dosimetry, Oncology, Radiobiology © RSNA, 2023.
Topics: United States; Male; Humans; Precision Medicine; Radiopharmaceuticals; Positron Emission Tomography Computed Tomography; Radioisotopes; Neoplasms
PubMed: 37477566
DOI: 10.1148/rycan.220157 -
Nature Mar 2024Memory encodes past experiences, thereby enabling future plans. The basolateral amygdala is a centre of salience networks that underlie emotional experiences and thus...
Memory encodes past experiences, thereby enabling future plans. The basolateral amygdala is a centre of salience networks that underlie emotional experiences and thus has a key role in long-term fear memory formation. Here we used spatial and single-cell transcriptomics to illuminate the cellular and molecular architecture of the role of the basolateral amygdala in long-term memory. We identified transcriptional signatures in subpopulations of neurons and astrocytes that were memory-specific and persisted for weeks. These transcriptional signatures implicate neuropeptide and BDNF signalling, MAPK and CREB activation, ubiquitination pathways, and synaptic connectivity as key components of long-term memory. Notably, upon long-term memory formation, a neuronal subpopulation defined by increased Penk and decreased Tac expression constituted the most prominent component of the memory engram of the basolateral amygdala. These transcriptional changes were observed both with single-cell RNA sequencing and with single-molecule spatial transcriptomics in intact slices, thereby providing a rich spatial map of a memory engram. The spatial data enabled us to determine that this neuronal subpopulation interacts with adjacent astrocytes, and functional experiments show that neurons require interactions with astrocytes to encode long-term memory.
Topics: Astrocytes; Basolateral Nuclear Complex; Brain-Derived Neurotrophic Factor; Cell Communication; Cyclic AMP Response Element-Binding Protein; Gene Expression Profiling; Memory, Long-Term; Mitogen-Activated Protein Kinases; Neurons; Sequence Analysis, RNA; Single Molecule Imaging; Single-Cell Gene Expression Analysis; Ubiquitination
PubMed: 38326616
DOI: 10.1038/s41586-023-07011-6 -
Nature Communications Nov 2023Understanding human disease on a molecular level, and translating this understanding into targeted diagnostics and therapies are central tenets of molecular medicine....
Understanding human disease on a molecular level, and translating this understanding into targeted diagnostics and therapies are central tenets of molecular medicine. Realizing this doctrine requires an efficient adaptation of molecular discoveries into the clinic. We present an approach to facilitate this process by describing the Imageable Genome, the part of the human genome whose expression can be assessed via molecular imaging. Using a deep learning-based hybrid human-AI pipeline, we bridge individual genes and their relevance in human diseases with specific molecular imaging methods. Cross-referencing the Imageable Genome with RNA-seq data from over 60,000 individuals reveals diagnostic, prognostic and predictive imageable genes for a wide variety of major human diseases. Having both the critical size and focus to be altered in its expression during the development and progression of any human disease, the Imageable Genome will generate new imaging tools that improve the understanding, diagnosis and management of human diseases.
Topics: Humans; Genome; Diagnostic Imaging
PubMed: 37957176
DOI: 10.1038/s41467-023-43123-3 -
Science (New York, N.Y.) Oct 2023Proteins and lipids decorated with glycans are found throughout biological entities, playing roles in biological functions and dysfunctions. Current analytical...
Proteins and lipids decorated with glycans are found throughout biological entities, playing roles in biological functions and dysfunctions. Current analytical strategies for these glycan-decorated biomolecules, termed glycoconjugates, rely on ensemble-averaged methods that do not provide a full view of positions and structures of glycans attached at individual sites in a given molecule, especially for glycoproteins. We show single-molecule analysis of glycoconjugates by direct imaging of individual glycoconjugate molecules using low-temperature scanning tunneling microscopy. Intact glycoconjugate ions from electrospray are soft-landed on a surface for their direct single-molecule imaging. The submolecular imaging resolution corroborated by quantum mechanical modeling unveils whole structures and attachment sites of glycans in glycopeptides, glycolipids, N-glycoproteins, and O-glycoproteins densely decorated with glycans.
Topics: Glycoconjugates; Glycolipids; Glycoproteins; Polysaccharides; Single Molecule Imaging; Mucin-1
PubMed: 37824645
DOI: 10.1126/science.adh3856 -
Cell Mar 2024To understand biological processes, it is necessary to reveal the molecular heterogeneity of cells by gaining access to the location and interaction of all biomolecules....
To understand biological processes, it is necessary to reveal the molecular heterogeneity of cells by gaining access to the location and interaction of all biomolecules. Significant advances were achieved by super-resolution microscopy, but such methods are still far from reaching the multiplexing capacity of proteomics. Here, we introduce secondary label-based unlimited multiplexed DNA-PAINT (SUM-PAINT), a high-throughput imaging method that is capable of achieving virtually unlimited multiplexing at better than 15 nm resolution. Using SUM-PAINT, we generated 30-plex single-molecule resolved datasets in neurons and adapted omics-inspired analysis for data exploration. This allowed us to reveal the complexity of synaptic heterogeneity, leading to the discovery of a distinct synapse type. We not only provide a resource for researchers, but also an integrated acquisition and analysis workflow for comprehensive spatial proteomics at single-protein resolution.
Topics: DNA; Microscopy, Fluorescence; Neurons; Proteins; Proteomics; Single Molecule Imaging
PubMed: 38552614
DOI: 10.1016/j.cell.2024.02.045 -
Journal of Nuclear Medicine : Official... Aug 2023The worldwide proliferation of persistent environmental pollutants is accelerating at an alarming rate. Not surprisingly, many of these pollutants pose a risk to human... (Review)
Review
The worldwide proliferation of persistent environmental pollutants is accelerating at an alarming rate. Not surprisingly, many of these pollutants pose a risk to human health. In this review, we examine recent literature in which molecular imaging and radiochemistry have been harnessed to study environmental pollutants. Specifically, these techniques offer unique ways to interrogate the pharmacokinetic profiles and bioaccumulation patterns of pollutants at environmentally relevant concentrations, thereby helping to determine their potential health risks.
Topics: Humans; Environmental Pollutants; Radiochemistry; Molecular Imaging
PubMed: 37442598
DOI: 10.2967/jnumed.122.265209