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Nature Reviews. Drug Discovery Jul 2023Substitution of a hydrogen atom with its heavy isotope deuterium entails the addition of one neutron to a molecule. Despite being a subtle change, this structural... (Review)
Review
Substitution of a hydrogen atom with its heavy isotope deuterium entails the addition of one neutron to a molecule. Despite being a subtle change, this structural modification, known as deuteration, may improve the pharmacokinetic and/or toxicity profile of drugs, potentially translating into improvements in efficacy and safety compared with the non-deuterated counterparts. Initially, efforts to exploit this potential primarily led to the development of deuterated analogues of marketed drugs through a 'deuterium switch' approach, such as deutetrabenazine, which became the first deuterated drug to receive FDA approval in 2017. In the past few years, the focus has shifted to applying deuteration in novel drug discovery, and the FDA approved the pioneering de novo deuterated drug deucravacitinib in 2022. In this Review, we highlight key milestones in the field of deuteration in drug discovery and development, emphasizing recent and instructive medicinal chemistry programmes and discussing the opportunities and hurdles for drug developers, as well as the questions that remain to be addressed.
Topics: Humans; Deuterium; Drug Discovery; Chemistry, Pharmaceutical
PubMed: 37277503
DOI: 10.1038/s41573-023-00703-8 -
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 -
CMAJ : Canadian Medical Association... Aug 2023
Topics: Humans; Radon; Lung Neoplasms
PubMed: 37553147
DOI: 10.1503/cmaj.230110-f -
Biomolecules Aug 2023Following previously published systematic reviews on the diagnostic use of nanoparticles (NPs), in this manuscript, we report published methods for radiolabeling... (Review)
Review
Following previously published systematic reviews on the diagnostic use of nanoparticles (NPs), in this manuscript, we report published methods for radiolabeling nanoparticles with therapeutic alpha-emitting, beta-emitting, or Auger's electron-emitting isotopes. After analyzing 234 papers, we found that different methods were used with the same isotope and the same type of nanoparticle. The most common type of nanoparticles used are the PLGA and PAMAM nanoparticles, and the most commonly used therapeutic isotope is Lu. Regarding labeling methods, the direct encapsulation of the isotope resulted in the most reliable and reproducible technique. Radiolabeled nanoparticles show promising results in metastatic breast and lung cancer, although this field of research needs more clinical studies, mainly on the comparison of nanoparticles with chemotherapy.
Topics: Dendrimers; Isotope Labeling; Nanomedicine; Nanoparticles; Radioisotopes
PubMed: 37627307
DOI: 10.3390/biom13081241 -
Molecules (Basel, Switzerland) Nov 2023The concept of theranostics uses radioisotopes of the same or chemically similar elements to label biological ligands in a way that allows the use of diagnostic and... (Review)
Review
The concept of theranostics uses radioisotopes of the same or chemically similar elements to label biological ligands in a way that allows the use of diagnostic and therapeutic radiation for a combined diagnosis and treatment regimen. For scandium, radioisotopes -43 and -44 can be used as diagnostic markers, while radioisotope scandium-47 can be used in the same configuration for targeted therapy. This work presents the latest achievements in the production and processing of radioisotopes and briefly characterizes solutions aimed at increasing the availability of these radioisotopes for research and clinical practice.
Topics: Radiopharmaceuticals; Scandium; Radioisotopes; Precision Medicine
PubMed: 38005390
DOI: 10.3390/molecules28227668 -
European Radiology Nov 2023
Topics: Humans; Gallium Radioisotopes; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18
PubMed: 37171487
DOI: 10.1007/s00330-023-09715-9 -
Data in Brief Oct 2023The present article introduces Zanadamu, a comprehensive geo-temporal-referenced dataset that amalgamates all published stable isotope carbon and oxygen measurements on...
The present article introduces Zanadamu, a comprehensive geo-temporal-referenced dataset that amalgamates all published stable isotope carbon and oxygen measurements on tooth enamel from African hominins, dated between 4.4 and 0.005 Ma. Zanadamu serves as a research tool for investigating hominin evolution by facilitating the examination of how different hominin species explored food resources and interacted with their local paleoenvironments. The dataset is structured in a machine-readable format, and its metadata organization allows for facile statistical analyses and comparisons with other types of isotopic records, including ancient and modern humans and other primates. Zanadamu is part of the AfriArch data initiative, which aims at compiling datasets for the study of ancient Africa. This an active initiative, and we strive to update Zanadamu as novel data becomes available.
PubMed: 37701712
DOI: 10.1016/j.dib.2023.109522 -
Cell Metabolism Oct 2023Stable isotopes are powerful tools to assess metabolism. C labeling is detected using nuclear magnetic resonance (NMR) spectroscopy or mass spectrometry (MS). MS has...
Stable isotopes are powerful tools to assess metabolism. C labeling is detected using nuclear magnetic resonance (NMR) spectroscopy or mass spectrometry (MS). MS has excellent sensitivity but generally cannot discriminate among different C positions (isotopomers), whereas NMR is less sensitive but reports some isotopomers. Here, we develop an MS method that reports all 16 aspartate and 32 glutamate isotopomers while requiring less than 1% of the sample used for NMR. This method discriminates between pathways that result in the same number of C labels in aspartate and glutamate, providing enhanced specificity over conventional MS. We demonstrate regional metabolic heterogeneity within human tumors, document the impact of fumarate hydratase (FH) deficiency in human renal cancers, and investigate the contributions of tricarboxylic acid (TCA) cycle turnover and CO recycling to isotope labeling in vivo. This method can accompany NMR or standard MS to provide outstanding sensitivity in isotope-labeling experiments, particularly in vivo.
Topics: Humans; Glutamic Acid; Aspartic Acid; Carbon Isotopes; Citric Acid Cycle; Mass Spectrometry
PubMed: 37611583
DOI: 10.1016/j.cmet.2023.07.013 -
PeerJ 2023Wildlife farming can be an important but complex tool for conservation. To achieve conservation benefits, wildlife farming should meet a variety of criteria, including... (Review)
Review
BACKGROUND
Wildlife farming can be an important but complex tool for conservation. To achieve conservation benefits, wildlife farming should meet a variety of criteria, including traceability conditions to identify the animals' origin. The traditional techniques for discriminating between wild and captive animals may be insufficient to prevent doubts or misdeclaration, especially when labels are not expected or mandatory. There is a pressing need to develop more accurate techniques to discriminate between wild and captive animals and their products. Stable isotope analysis has been used to identify animal provenance, and some studies have successfully demonstrated its potential to differentiate wild from captive animals. In this literature review, we examined an extensive collection of publications to develop an overall picture of the application of stable isotopes to distinguish between wild and captive animals focusing on evaluating the patterns and potential of this tool.
SURVEY METHODOLOGY
We searched peer-reviewed publications in the Web of Science database and the references list from the main studies on the subject. We selected and analyzed 47 studies that used C, N, H, O, and S in tissues from fish, amphibians, reptiles, birds, and mammals. We built a database from the isotope ratios and metadata extracted from the publications.
RESULTS
Studies have been using stable isotopes in wild and captive animals worldwide, with a particular concentration in Europe, covering all main vertebrate groups. A total of 80.8% of the studies combined stable isotopes of carbon and nitrogen, and 88.2% used at least one of those elements. Fish is the most studied group, while amphibians are the least. Muscle and inert organic structures were the most analyzed tissues (46.81% and 42.55%). C and N standard deviation and range were significantly higher in the wild than in captive animals, suggesting a more variable diet in the first group. C tended to be higher in wild fishes and in captive mammals, birds, reptiles, and amphibians. N was higher in the wild terrestrial animals when controlling for diet. Only 5.7% of the studies failed to differentiate wild and captive animals using stable isotopes.
CONCLUSIONS
This review reveals that SIA can help distinguish between wild and captive in different vertebrate groups, rearing conditions, and methodological designs. Some aspects should be carefully considered to use the methodology properly, such as the wild and captivity conditions, the tissue analyzed, and how homogeneous the samples are. Despite the increased use of SIA to distinguish wild from captive animals, some gaps remain since some taxonomic groups (., amphibians), countries (., Africa), and isotopes (., H, O, and S) have been little studied.
Topics: Animals; Carbon Isotopes; Nitrogen Isotopes; Animals, Wild; Carbon; Fishes; Mammals
PubMed: 38025752
DOI: 10.7717/peerj.16460 -
Seminars in Nuclear Medicine Sep 2023Fibroblast activation protein inhibitor (FAPI) is a promising tracer in oncologic positron emission tomography/computed tomography (PET/CT). Numerous studies have... (Review)
Review
Fibroblast activation protein inhibitor (FAPI) is a promising tracer in oncologic positron emission tomography/computed tomography (PET/CT). Numerous studies have demonstrated the superior sensitivity of FAPI PET/CT over fluorodeoxyglucose (FDG) PET/CT in several types of cancer. However, the cancer specificity of FAPI uptake remains understudied, and several cases of false-positive FAPI PET/CT findings have been reported. A systematic search of PubMed, Embase, and Web of Science was conducted for studies published prior to April 2022 reporting nonmalignant FAPI PET/CT findings. We included original peer-reviewed articles of studies in humans using FAPI tracers radiolabeled with Ga or F that were published in English. Papers without original data and studies with insufficient information were excluded. Nonmalignant findings were presented on a per-lesion basis and grouped according to the type of organ or tissue involved. The search identified a total of 1.178 papers, of which 108 studies were eligible. Eighty studies were case reports (74%), and the remaining 28 were cohort studies (26%). A total of 2.372 FAPI-avid nonmalignant findings were reported, with the most frequent being uptake in the arteries, e.g., related to plaques (n = 1178, 49%). FAPI uptake was also frequently related to degenerative and traumatic bone and joint lesions (n = 147, 6%) or arthritis (n = 92, 4%). For organs, diffuse or focal uptake was often seen in cases of inflammation, infection, fibrosis, and IgG4-related disease (n = 157, 7%). FAPI-avid inflammatory/reactive lymph nodes (n = 121, 5%) and tuberculosis lesions (n = 51, 2%) have been reported and could prove to be potential pitfalls in cancer staging. Periodontitis (n = 76, 3%), hemorrhoids (n = 47, 2%), and scarring/wound healing (n = 35, 2%) also presented as focal uptake on FAPI PET/CT. The present review provides an overview of the reported FAPI-avid nonmalignant PET/CT findings to date. A large number of benign clinical entities may show FAPI uptake and should be kept in mind when interpreting FAPI PET/CT findings in patients with cancer.
Topics: Humans; Biological Transport; Fluorodeoxyglucose F18; Gallium Radioisotopes; Inflammation; Positron Emission Tomography Computed Tomography
PubMed: 36813670
DOI: 10.1053/j.semnuclmed.2023.02.001