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Diagnostic Tools for Neuropsychological Disorders
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Diagnostic Tools for Neuropsychological Disorders

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 20 January 2025 | Viewed by 5117

Special Issue Editor

Dr. Behrooz Hooshyar Yousefi

E-Mail Website
Guest Editor
Department of Nuclear Medicine, School of Medicine, Philipps University Marburg, 35043 Marburg, Germany
Interests: radiotracer development; molecular imaging; neuropsychological disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Molecular research in psychiatry comprises the development of diagnostic tools for neuropsychological disorders. It is an exciting field that aims to comprehend, diagnose, treat, and investigate brain diseases, as well as mind and behavioral disorders. It includes the visualization and/or measurement of the causes and hallmarks of diseases using biological or biochemical processes at the cellular and molecular levels. As an interdisciplinary field between neurology and psychology, psychiatry benefits from contributions from many fields such as neuroscience, pharmacology, medicine, molecular imaging, biology, biochemistry, pathology, and psychology, with the aid of in silico, in vitro, and preclinical models, as well as in living humans.

This Special Issue focuses on developing and implementing molecular imaging strategies for research in “Neuropsychological Disorders”. Molecular imaging techniques include the design, development, and evaluation of diagnostics tools by means of nuclear medicine, optical and optoacoustic methods, ultrasound, molecular computed tomography, magnetic resonance imaging, and spectroscopy. We welcome original research and review articles.

Dr. Behrooz Hooshyar Yousefi
Guest Editor

Manuscript Submission Information

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Keywords

  • radiotracer development
  • molecular imaging
  • multimodal imaging
  • PET/SPECT/CT/MRI
  • optical imaging
  • neuropsychological disorders
  • β-amyloidopathy
  • tauopathies
  • α-synucleinopathies

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Published Papers (3 papers)

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Research

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12 pages, 4240 KiB  
Article
Labeling of Bruton’s Tyrosine Kinase (BTK) Inhibitor [11C]BIO-2008846 in Three Different Positions and Measurement in NHP Using PET
by Sangram Nag, Prodip Datta, Anton Forsberg Morén, Yasir Khani, Laurent Martarello, Maciej Kaliszczak and Christer Halldin
Int. J. Mol. Sci. 2024, 25(14), 7870; https://doi.org/10.3390/ijms25147870 - 18 Jul 2024
Viewed by 839
Abstract
Bruton’s tyrosine kinase (BTK) is pivotal in B-cell signaling and a target for potential anti-cancer and immunological disorder therapies. Improved selective reversible BTK inhibitors are in demand due to the absence of direct BTK engagement measurement tools. Promisingly, PET imaging can non-invasively evaluate [...] Read more.
Bruton’s tyrosine kinase (BTK) is pivotal in B-cell signaling and a target for potential anti-cancer and immunological disorder therapies. Improved selective reversible BTK inhibitors are in demand due to the absence of direct BTK engagement measurement tools. Promisingly, PET imaging can non-invasively evaluate BTK expression. In this study, radiolabeled BIO-2008846 ([11C]BIO-2008846-A), a BTK inhibitor, was used for PET imaging in NHPs to track brain biodistribution. Radiolabeling BIO-2008846 with carbon-11, alongside four PET scans on two NHPs each, showed a homogeneous distribution of [11C]BIO-2008846-A in NHP brains. Brain uptake ranged from 1.8% ID at baseline to a maximum of 3.2% post-pretreatment. The study found no significant decrease in regional VT values post-dose, implying minimal specific binding of [11C]BIO-2008846-A compared to free and non-specific components in the brain. Radiometabolite analysis revealed polar metabolites with 10% unchanged radioligand after 30 min. The research highlighted strong brain uptake despite minor distribution variability, confirming passive diffusion kinetics dominated by free and non-specific binding. Full article
(This article belongs to the Special Issue Diagnostic Tools for Neuropsychological Disorders)
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22 pages, 4689 KiB  
Article
In Silico and In Vitro Study towards the Rational Design of 4,4′-Disarylbisthiazoles as a Selective α-Synucleinopathy Biomarker
by Bright C. Uzuegbunam, Junhao Li, Wojciech Paslawski, Wolfgang Weber, Per Svenningsson, Hans Ågren and Behrooz Hooshyar Yousefi
Int. J. Mol. Sci. 2023, 24(22), 16445; https://doi.org/10.3390/ijms242216445 - 17 Nov 2023
Viewed by 1217
Abstract
The α-synucleinopathies are a group of neurodegenerative diseases characterized by the deposition of α-synuclein aggregates (α-syn) in the brain. Currently, there is no suitable tracer to enable a definitive early diagnosis of these diseases. We reported candidates based on 4,4′-disarylbisthiazole (DABTA) scaffold with [...] Read more.
The α-synucleinopathies are a group of neurodegenerative diseases characterized by the deposition of α-synuclein aggregates (α-syn) in the brain. Currently, there is no suitable tracer to enable a definitive early diagnosis of these diseases. We reported candidates based on 4,4′-disarylbisthiazole (DABTA) scaffold with a high affinity towards α-syn and excellent selectivity over Aβ and tau fibrils. Based on prior in silico studies, a focused library of 23 halogen-containing and O-methylated DABTAs was prepared. The DABTAs were synthesized via a modified two-step Hantzsch thiazole synthesis, characterized, and used in competitive binding assays against [3H]PiB and [3H]DCVJ. The DABTAs were obtained with an overall chemical yield of 15–71%, and showed a calculated lipophilicity of 2.5–5.7. The ligands demonstrated an excellent affinity to α-syn with both [3H]PiB and [3H]DCVJ: Ki 0.1–4.9 nM and up to 20–3900-fold selectivity over Aβ and tau fibrils. It could be concluded that in silico simulation is useful for the rational design of a new generation of DABTAs. Further investigation of the leads in the next step is encouraged: radiolabeling of the ligands with radioisotopes such as fluorine-18 or carbon-11 for in vivo, ex vivo, and translational research and for further in vitro experiments on human-derived protein aggregates. Full article
(This article belongs to the Special Issue Diagnostic Tools for Neuropsychological Disorders)
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Review

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33 pages, 2284 KiB  
Review
Radiotracers for Imaging of Inflammatory Biomarkers TSPO and COX-2 in the Brain and in the Periphery
by Bright Chukwunwike Uzuegbunam, Christoph Rummel, Damiano Librizzi, Carsten Culmsee and Behrooz Hooshyar Yousefi
Int. J. Mol. Sci. 2023, 24(24), 17419; https://doi.org/10.3390/ijms242417419 - 13 Dec 2023
Cited by 3 | Viewed by 2347
Abstract
Inflammation involves the activation of innate immune cells and is believed to play an important role in the development and progression of both infectious and non-infectious diseases such as neurodegeneration, autoimmune diseases, pulmonary and cancer. Inflammation in the brain is marked by the [...] Read more.
Inflammation involves the activation of innate immune cells and is believed to play an important role in the development and progression of both infectious and non-infectious diseases such as neurodegeneration, autoimmune diseases, pulmonary and cancer. Inflammation in the brain is marked by the upregulation of translocator protein (TSPO) in microglia. High TSPO levels are also found, for example, in macrophages in cases of rheumatoid arthritis and in malignant tumor cells compared to their relatively low physiological expression. The same applies for cyclooxgenase-2 (COX-2), which is constitutively expressed in the kidney, brain, thymus and gastrointestinal tract, but induced in microglia, macrophages and synoviocytes during inflammation. This puts TSPO and COX-2 in the spotlight as important targets for the diagnosis of inflammation. Imaging modalities, such as positron emission tomography and single-photon emission tomography, can be used to localize inflammatory processes and to track their progression over time. They could also enable the monitoring of the efficacy of therapy and predict its outcome. This review focuses on the current development of PET and SPECT tracers, not only for the detection of neuroinflammation, but also for emerging diagnostic measures in infectious and other non-infectious diseases such as rheumatic arthritis, cancer, cardiac inflammation and in lung diseases. Full article
(This article belongs to the Special Issue Diagnostic Tools for Neuropsychological Disorders)
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