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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 Jul 2023Proteins and nucleic acids can phase-separate in the cell to form concentrated biomolecular condensates. The functions of condensates span many length scales: they...
Proteins and nucleic acids can phase-separate in the cell to form concentrated biomolecular condensates. The functions of condensates span many length scales: they modulate interactions and chemical reactions at the molecular scale, organize biochemical processes at the mesoscale and compartmentalize cells. Understanding the underlying mechanisms of these processes will require detailed knowledge of the rich dynamics across these scales. The mesoscopic dynamics of biomolecular condensates have been extensively characterized, but their behaviour at the molecular scale has remained more elusive. Here, as an example of biomolecular phase separation, we study complex coacervates of two highly and oppositely charged disordered human proteins. Their dense phase is 1,000 times more concentrated than the dilute phase, and the resulting percolated interaction network leads to a bulk viscosity 300 times greater than that of water. However, single-molecule spectroscopy optimized for measurements within individual droplets reveals that at the molecular scale, the disordered proteins remain exceedingly dynamic, with their chain configurations interconverting on submicrosecond timescales. Massive all-atom molecular dynamics simulations reproduce the experimental observations and explain this apparent discrepancy: the underlying interactions between individual charged side chains are short-lived and exchange on a pico- to nanosecond timescale. Our results indicate that, despite the high macroscopic viscosity of phase-separated systems, local biomolecular rearrangements required for efficient reactions at the molecular scale can remain rapid.
Topics: Humans; Biomolecular Condensates; Molecular Dynamics Simulation; Water; Time Factors; Viscosity; Single Molecule Imaging; Intrinsically Disordered Proteins
PubMed: 37468629
DOI: 10.1038/s41586-023-06329-5 -
The Journal of Thoracic and... Dec 2023The study objective was to determine the clinical utility of pafolacianine, a folate receptor-targeted fluorescent agent, in revealing by intraoperative molecular... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
The study objective was to determine the clinical utility of pafolacianine, a folate receptor-targeted fluorescent agent, in revealing by intraoperative molecular imaging folate receptor α positive cancers in the lung and narrow surgical margins that may otherwise be undetected with conventional visualization.
METHODS
In this Phase 3, 12-center trial, 112 patients with suspected or biopsy-confirmed cancer in the lung scheduled for sublobar pulmonary resection were administered intravenous pafolacianine within 24 hours before surgery. Participants were randomly assigned to surgery with or without intraoperative molecular imaging (10:1 ratio). The primary end point was the proportion of participants with a clinically significant event, reflecting a meaningful change in the surgical operation.
RESULTS
No drug-related serious adverse events occurred. One or more clinically significant event occurred in 53% of evaluated participants compared with a prespecified limit of 10% (P < .0001). In 38 participants, at least 1 event was a margin 10 mm or less from the resected primary nodule (38%, 95% confidence interval, 28.5-48.3), 32 being confirmed by histopathology. In 19 subjects (19%, 95% confidence interval, 11.8-28.1), intraoperative molecular imaging located the primary nodule that the surgeon could not locate with white light and palpation. Intraoperative molecular imaging revealed 10 occult synchronous malignant lesions in 8 subjects (8%, 95% confidence interval, 3.5-15.2) undetected using white light. Most (73%) intraoperative molecular imaging-discovered synchronous malignant lesions were outside the planned resection field. A change in the overall scope of surgical procedure occurred for 29 of the subjects (22 increase, 7 decrease).
CONCLUSIONS
Intraoperative molecular imaging with pafolacianine improves surgical outcomes by identifying occult tumors and close surgical margins.
Topics: Humans; Margins of Excision; Lung; Lung Neoplasms; Molecular Imaging
PubMed: 37019717
DOI: 10.1016/j.jtcvs.2023.02.025 -
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 -
European Journal of Nuclear Medicine... Nov 2023
Topics: Humans; Precision Medicine; Theranostic Nanomedicine; Molecular Imaging
PubMed: 37646834
DOI: 10.1007/s00259-023-06415-w -
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