Submit to Molecules Review for Molecules Propose a Special Issue

Journal Browser

► Journal Browser

Radiolabelled Molecules for Brain Imaging with PET and SPECT

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (5 January 2020) | Viewed by 58968

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special issue Radiolabelled Molecules for Brain Imaging with PET and SPECT book cover image

Share This Special Issue

Special Issue Editor

Prof. Dr. Peter Brust

E-Mail Website
Guest Editor

Department of Neuroradiopharmaceuticals, Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Permoserstraße 15, 04318 Leipzig, Germany
Interests: radiotracer development for brain tumor imaging (glioblastoma, brain metastases); neuroimaging of the cholinergic system (nicotinic acetylcholine receptors, vesicular acetylcholine transporter); neuroimaging of second messenger systems (phosphodiesterases 2, 5, and 10); neuroimaging of neuromodulatory processes (sigma and cannabinoid receptors, adenosine signaling); blood–brain barrier transport of radiopharmaceuticals
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are in vivo molecular imaging tools which are widely used in nuclear medicine for the diagnosis and treatment follow-up of many brain diseases, including neurodegenerative disorders, such as Alzheimer's and Parkinson's disease, psychiatric syndromes, such as major depression and schizophrenia, or brain tumors, with glioblastoma multiforme as the most aggressive type of brain-derived cancers. The success of PET and SPECT imaging very much depends on the suitability of imaging probes, which are labeled with radionuclides of short half-lives. The delivery of those radiotracers to the brain and their subsequent quantification with PET and SPECT provides images of biochemical processes such as transport, metabolism, and neurotransmission on the molecular level. In addition to the diagnostic and therapeutic use as radiopharmaceuticals, in the field of nuclear medicine, they provide powerful tools for in vivo pharmacology during the process of preclinical drug development to identify new drug targets, to investigate the pathophysiology, to discover potential drug candidates, and to evaluate the pharmacokinetics and pharmacodynamics of drugs in vivo. Furthermore, they allow molecular imaging studies in various small-animal models of disease, including genetically-engineered animals.

All researchers working in this very interdisciplinary field are cordially invited to contribute original research papers or reviews to this Special Issue of Molecules, which is related to the development and use of radiolabeled molecules for brain imaging.

Prof. Dr. Peter Brust
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

PET
SPECT
Carbon-11
Fluorine-18
Radiolabelled iodine
Technetium-99m
Gallium-64
Alzheimer´s disease
Parkinson´s disease
Depression
Schizophrenia
Brain cancer
Glioblastoma

Published Papers (11 papers)

Download All Papers

Research

Jump to: Review, Other

15 pages, 2980 KiB

Open AccessArticle

PET Imaging of the Adenosine A_2A Receptor in the Rotenone-Based Mouse Model of Parkinson’s Disease with [¹⁸F]FESCH Synthesized by a Simplified Two-Step One-Pot Radiolabeling Strategy

by Susann Schröder, Thu Hang Lai, Magali Toussaint, Mathias Kranz, Alexandra Chovsepian, Qi Shang, Sladjana Dukić-Stefanović, Winnie Deuther-Conrad, Rodrigo Teodoro, Barbara Wenzel, Rareş-Petru Moldovan, Francisco Pan-Montojo and Peter Brust

Molecules 2020, 25(7), 1633; https://doi.org/10.3390/molecules25071633 - 2 Apr 2020

Cited by 14 | Viewed by 3848

Abstract

The adenosine A_2A receptor (A_2AR) is regarded as a particularly appropriate target for non-dopaminergic treatment of Parkinson’s disease (PD). An increased A_2AR availability has been found in the human striatum at early stages of PD and in patients with PD and dyskinesias. The aim of this small animal positron emission tomography/magnetic resonance (PET/MR) imaging study was to investigate whether rotenone-treated mice reflect the aspect of striatal A_2AR upregulation in PD. For that purpose, we selected the known A_2AR-specific radiotracer [¹⁸F]FESCH and developed a simplified two-step one-pot radiosynthesis. PET images showed a high uptake of [¹⁸F]FESCH in the mouse striatum. Concomitantly, metabolism studies with [¹⁸F]FESCH revealed the presence of a brain-penetrant radiometabolite. In rotenone-treated mice, a slightly higher striatal A_2AR binding of [¹⁸F]FESCH was found. Nonetheless, the correlation between the increased A_2AR levels within the proposed PD animal model remains to be further investigated. Full article

(This article belongs to the Special Issue Radiolabelled Molecules for Brain Imaging with PET and SPECT)

► Show Figures

Graphical abstract

19 pages, 3067 KiB

Open AccessArticle

In Vitro and In Vivo Characterization of Dibenzothiophene Derivatives [¹²⁵I]Iodo-ASEM and [¹⁸F]ASEM as Radiotracers of Homo- and Heteromeric α7 Nicotinic Acetylcholine Receptors

by Cornelius K. Donat, Henrik H. Hansen, Hanne D. Hansen, Ronnie C. Mease, Andrew G. Horti, Martin G. Pomper, Elina T. L’Estrade, Matthias M. Herth, Dan Peters, Gitte M. Knudsen and Jens D. Mikkelsen

Molecules 2020, 25(6), 1425; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25061425 - 20 Mar 2020

Cited by 9 | Viewed by 3501

Abstract

The α7 nicotinic acetylcholine receptor (α7 nAChR) is involved in several cognitive and physiologic processes; its expression levels and patterns change in neurologic and psychiatric diseases, such as schizophrenia and Alzheimer’s disease, which makes it a relevant drug target. Development of selective radioligands is important for defining binding properties and occupancy of novel molecules targeting the receptor. We tested the in vitro binding properties of [¹²⁵I]Iodo-ASEM [(3-(1,4-diazabycyclo[3.2.2]nonan-4-yl)-6-(¹²⁵I-iododibenzo[b,d]thiopentene 5,5-dioxide)] in the mouse, rat and pig brain using autoradiography. The in vivo binding properties of [¹⁸F]ASEM were investigated using positron emission tomography (PET) in the pig brain. [¹²⁵I]Iodo-ASEM showed specific and displaceable high affinity (~1 nM) binding in mouse, rat, and pig brain. Binding pattern overlapped with [¹²⁵I]α-bungarotoxin, specific binding was absent in α7 nAChR gene-deficient mice and binding was blocked by a range of α7 nAChR orthosteric modulators in an affinity-dependent order in the pig brain. Interestingly, relative to the wild-type, binding in β2 nAChR gene-deficient mice was lower for [¹²⁵I]Iodo-ASEM (58% ± 2.7%) than [¹²⁵I]α-bungarotoxin (23% ± 0.2%), potentially indicating different binding properties to heteromeric α7β2 nAChR. [¹⁸F]ASEM PET in the pig showed high brain uptake and reversible tracer kinetics with a similar spatial distribution as previously reported for α7 nAChR. Blocking with SSR-180,711 resulted in a significant decrease in [¹⁸F]ASEM binding. Our findings indicate that [¹²⁵I]Iodo-ASEM allows sensitive and selective imaging of α7 nAChR in vitro, with better signal-to-noise ratio than previous tracers. Preliminary data of [¹⁸F]ASEM in the pig brain demonstrated principal suitable kinetic properties for in vivo quantification of α7 nAChR, comparable to previously published data. Full article

(This article belongs to the Special Issue Radiolabelled Molecules for Brain Imaging with PET and SPECT)

► Show Figures

Graphical abstract

17 pages, 4893 KiB

Open AccessArticle

Radiosynthesis and Biological Investigation of a Novel Fluorine-18 Labeled Benzoimidazotriazine-Based Radioligand for the Imaging of Phosphodiesterase 2A with Positron Emission Tomography

by Rien Ritawidya, Barbara Wenzel, Rodrigo Teodoro, Magali Toussaint, Mathias Kranz, Winnie Deuther-Conrad, Sladjana Dukic-Stefanovic, Friedrich-Alexander Ludwig, Matthias Scheunemann and Peter Brust

Molecules 2019, 24(22), 4149; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24224149 - 15 Nov 2019

Cited by 5 | Viewed by 3535

Abstract

A specific radioligand for the imaging of cyclic nucleotide phosphodiesterase 2A (PDE2A) via positron emission tomography (PET) would be helpful for research on the physiology and disease-related changes in the expression of this enzyme in the brain. In this report, the radiosynthesis of a novel PDE2A radioligand and the subsequent biological evaluation were described. Our prospective compound 1-(2-chloro-5-methoxy phenyl)-8-(2-fluoropyridin-4-yl)-3- methylbenzo[e]imidazo[5,1-c][1,2,4]triazine, benzoimidazotriazine (BIT1) (IC₅₀ PDE2A = 3.33 nM; 16-fold selectivity over PDE10A) was fluorine-18 labeled via aromatic nucleophilic substitution of the corresponding nitro precursor using the K[¹⁸F]F-K_2.2.2-carbonate complex system. The new radioligand [¹⁸F]BIT1 was obtained with a high radiochemical yield (54 ± 2%, n = 3), a high radiochemical purity (≥99%), and high molar activities (155–175 GBq/μmol, n = 3). In vitro autoradiography on pig brain cryosections exhibited a heterogeneous spatial distribution of [¹⁸F]BIT1 corresponding to the known pattern of expression of PDE2A. The investigation of in vivo metabolism of [¹⁸F]BIT1 in a mouse revealed sufficient metabolic stability. PET studies in mouse exhibited a moderate brain uptake of [¹⁸F]BIT1 with a maximum standardized uptake value of ~0.7 at 5 min p.i. However, in vivo blocking studies revealed a non-target specific binding of [¹⁸F]BIT1. Therefore, further structural modifications are needed to improve target selectivity. Full article

(This article belongs to the Special Issue Radiolabelled Molecules for Brain Imaging with PET and SPECT)

► Show Figures

Figure 1

21 pages, 1456 KiB

Open AccessArticle

Synthesis and In Vitro Evaluation of 8-Pyridinyl-Substituted Benzo[e]imidazo[2,1-c][1,2,4]triazines as Phosphodiesterase 2A Inhibitors

by Rien Ritawidya, Friedrich-Alexander Ludwig, Detlef Briel, Peter Brust and Matthias Scheunemann

Molecules 2019, 24(15), 2791; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24152791 - 31 Jul 2019

Cited by 9 | Viewed by 3536

Abstract

Phosphodiesterase 2A (PDE2A) is highly expressed in distinct areas of the brain, which are known to be related to neuropsychiatric diseases. The development of suitable PDE2A tracers for Positron Emission Tomography (PET) would permit the in vivo imaging of the PDE2A and evaluation of disease-mediated alterations of its expression. A series of novel fluorinated PDE2A inhibitors on the basis of a Benzoimidazotriazine (BIT) scaffold was prepared leading to a prospective inhibitor for further development of a PDE2A PET imaging agent. BIT derivatives (BIT1–9) were obtained by a seven-step synthesis route, and their inhibitory potency towards PDE2A and selectivity over other PDEs were evaluated. BIT1 demonstrated much higher inhibition than other BIT derivatives (82.9% inhibition of PDE2A at 10 nM). BIT1 displayed an IC₅₀ for PDE2A of 3.33 nM with 16-fold selectivity over PDE10A. This finding revealed that a derivative bearing both a 2-fluoro-pyridin-4-yl and 2-chloro-5-methoxy-phenyl unit at the 8- and 1-position, respectively, appeared to be the most potent inhibitor. In vitro studies of BIT1 using mouse liver microsomes (MLM) disclosed BIT1 as a suitable ligand for ¹⁸F-labeling. Nevertheless, future in vivo metabolism studies are required. Full article

(This article belongs to the Special Issue Radiolabelled Molecules for Brain Imaging with PET and SPECT)

► Show Figures

Figure 1

14 pages, 2667 KiB

Open AccessArticle

Metabolic Brain Network Analysis of FDG-PET in Alzheimer’s Disease Using Kernel-Based Persistent Features

by Liqun Kuang, Deyu Zhao, Jiacheng Xing, Zhongyu Chen, Fengguang Xiong and Xie Han

Molecules 2019, 24(12), 2301; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24122301 - 21 Jun 2019

Cited by 11 | Viewed by 4096

Abstract

Recent research of persistent homology in algebraic topology has shown that the altered network organization of human brain provides a promising indicator of many neuropsychiatric disorders and neurodegenerative diseases. However, the current slope-based approach may not accurately characterize changes of persistent features over graph filtration because such curves are not strictly linear. Moreover, our previous integrated persistent feature (IPF) works well on an rs-fMRI cohort while it has not yet been studied on metabolic brain networks. To address these issues, we propose a novel univariate network measurement, kernel-based IPF (KBI), based on the prior IPF, to quantify the difference between IPF curves. In our experiments, we apply the KBI index to study fluorodeoxyglucose positron emission tomography (FDG-PET) imaging data from 140 subjects with Alzheimer’s disease (AD), 280 subjects with mild cognitive impairment (MCI), and 280 healthy normal controls (NC). The results show the disruption of network integration in the progress of AD. Compared to previous persistent homology-based measures, as well as other standard graph-based measures that characterize small-world organization and modular structure, our proposed network index KBI possesses more significant group difference and better classification performance, suggesting that it may be used as an effective preclinical AD imaging biomarker. Full article

(This article belongs to the Special Issue Radiolabelled Molecules for Brain Imaging with PET and SPECT)

► Show Figures

Graphical abstract

12 pages, 1715 KiB

Open AccessArticle

Evaluating the In Vivo Specificity of [¹⁸F]UCB-H for the SV2A Protein, Compared with SV2B and SV2C in Rats Using microPET

by Maria Elisa Serrano, Guillaume Becker, Mohamed Ali Bahri, Alain Seret, Nathalie Mestdagh, Joël Mercier, Frédéric Mievis, Fabrice Giacomelli, Christian Lemaire, Eric Salmon, André Luxen and Alain Plenevaux

Molecules 2019, 24(9), 1705; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24091705 - 1 May 2019

Cited by 10 | Viewed by 3797

Abstract

The synaptic vesicle protein 2 (SV2) is involved in synaptic vesicle trafficking. The SV2A isoform is the most studied and its implication in epilepsy therapy led to the development of the first SV2A PET radiotracer [¹⁸F]UCB-H. The objective of this study was to evaluate in vivo, using microPET in rats, the specificity of [¹⁸F]UCB-H for SV2 isoform A in comparison with the other two isoforms (B and C) through a blocking assay. Twenty Sprague Dawley rats were pre-treated either with the vehicle, or with specific competitors against SV2A (levetiracetam), SV2B (UCB5203) and SV2C (UCB0949). The distribution volume (Vt, Logan plot, t* 15 min) was obtained with a population-based input function. The Vt analysis for the entire brain showed statistically significant differences between the levetiracetam group and the other groups (p < 0.001), but also between the vehicle and the SV2B group (p < 0.05). An in-depth Vt analysis conducted for eight relevant brain structures confirmed the statistically significant differences between the levetiracetam group and the other groups (p < 0.001) and highlighted the superior and the inferior colliculi along with the cortex as regions also displaying statistically significant differences between the vehicle and SV2B groups (p < 0.05). These results emphasize the in vivo specificity of [¹⁸F]UCB-H for SV2A against SV2B and SV2C, confirming that [¹⁸F]UCB-H is a suitable radiotracer for in vivo imaging of the SV2A proteins with PET. Full article

(This article belongs to the Special Issue Radiolabelled Molecules for Brain Imaging with PET and SPECT)

► Show Figures

Figure 1

Review

Jump to: Research, Other

25 pages, 1679 KiB

Open AccessReview

Current Landscape and Emerging Fields of PET Imaging in Patients with Brain Tumors

by Jan-Michael Werner, Philipp Lohmann, Gereon R. Fink, Karl-Josef Langen and Norbert Galldiks

Molecules 2020, 25(6), 1471; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25061471 - 24 Mar 2020

Cited by 30 | Viewed by 5713

Abstract

The number of positron-emission tomography (PET) tracers used to evaluate patients with brain tumors has increased substantially over the last years. For the management of patients with brain tumors, the most important indications are the delineation of tumor extent (e.g., for planning of resection or radiotherapy), the assessment of treatment response to systemic treatment options such as alkylating chemotherapy, and the differentiation of treatment-related changes (e.g., pseudoprogression or radiation necrosis) from tumor progression. Furthermore, newer PET imaging approaches aim to address the need for noninvasive assessment of tumoral immune cell infiltration and response to immunotherapies (e.g., T-cell imaging). This review summarizes the clinical value of the landscape of tracers that have been used in recent years for the above-mentioned indications and also provides an overview of promising newer tracers for this group of patients. Full article

(This article belongs to the Special Issue Radiolabelled Molecules for Brain Imaging with PET and SPECT)

► Show Figures

Figure 1

35 pages, 1656 KiB

Open AccessReview

PET Radiopharmaceuticals for Alzheimer’s Disease and Parkinson’s Disease Diagnosis, the Current and Future Landscape

by Bright Chukwunwike Uzuegbunam, Damiano Librizzi and Behrooz Hooshyar Yousefi

Molecules 2020, 25(4), 977; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25040977 - 21 Feb 2020

Cited by 67 | Viewed by 11034

Abstract

Ironically, population aging which is considered a public health success has been accompanied by a myriad of new health challenges, which include neurodegenerative disorders (NDDs), the incidence of which increases proportionally to age. Among them, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common, with the misfolding and the aggregation of proteins being common and causal in the pathogenesis of both diseases. AD is characterized by the presence of hyperphosphorylated τ protein (tau), which is the main component of neurofibrillary tangles (NFTs), and senile plaques the main component of which is β-amyloid peptide aggregates (Aβ). The neuropathological hallmark of PD is α-synuclein aggregates (α-syn), which are present as insoluble fibrils, the primary structural component of Lewy body (LB) and neurites (LN). An increasing number of non-invasive PET examinations have been used for AD, to monitor the pathological progress (hallmarks) of disease. Notwithstanding, still the need for the development of novel detection tools for other proteinopathies still remains. This review, although not exhaustively, looks at the timeline of the development of existing tracers used in the imaging of Aβ and important moments that led to the development of these tracers. Full article

(This article belongs to the Special Issue Radiolabelled Molecules for Brain Imaging with PET and SPECT)

► Show Figures

Figure 1

19 pages, 1569 KiB

Open AccessReview

Approaches to PET Imaging of Glioblastoma

by Lindsey R. Drake, Ansel T. Hillmer and Zhengxin Cai

Molecules 2020, 25(3), 568; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25030568 - 28 Jan 2020

Cited by 42 | Viewed by 6242

Abstract

Glioblastoma multiforme (GBM) is the deadliest type of brain tumor, affecting approximately three in 100,000 adults annually. Positron emission tomography (PET) imaging provides an important non-invasive method of measuring biochemically specific targets at GBM lesions. These powerful data can characterize tumors, predict treatment effectiveness, and monitor treatment. This review will discuss the PET imaging agents that have already been evaluated in GBM patients so far, and new imaging targets with promise for future use. Previously used PET imaging agents include the tracers for markers of proliferation ([¹¹C]methionine; [¹⁸F]fluoro-ethyl-L-tyrosine, [¹⁸F]Fluorodopa, [¹⁸F]fluoro-thymidine, and [¹⁸F]clofarabine), hypoxia sensing ([¹⁸F]FMISO, [¹⁸F]FET-NIM, [¹⁸F]EF5, [¹⁸F]HX4, and [⁶⁴Cu]ATSM), and ligands for inflammation. As cancer therapeutics evolve toward personalized medicine and therapies centered on tumor biomarkers, the development of complimentary selective PET agents can dramatically enhance these efforts. Newer biomarkers for GBM PET imaging are discussed, with some already in use for PET imaging other cancers and neurological disorders. These targets include Sigma 1, Sigma 2, programmed death ligand 1, poly-ADP-ribose polymerase, and isocitrate dehydrogenase. For GBM, these imaging agents come with additional considerations such as blood–brain barrier penetration, quantitative modeling approaches, and nonspecific binding. Full article

(This article belongs to the Special Issue Radiolabelled Molecules for Brain Imaging with PET and SPECT)

► Show Figures

Figure 1

35 pages, 4351 KiB

Open AccessReview

A Survey of Molecular Imaging of Opioid Receptors

by Paul Cumming, János Marton, Tuomas O. Lilius, Dag Erlend Olberg and Axel Rominger

Molecules 2019, 24(22), 4190; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules24224190 - 19 Nov 2019

Cited by 32 | Viewed by 9442

Abstract

The discovery of endogenous peptide ligands for morphine binding sites occurred in parallel with the identification of three subclasses of opioid receptor (OR), traditionally designated as μ, δ, and κ, along with the more recently defined opioid-receptor-like (ORL1) receptor. Early efforts in opioid receptor radiochemistry focused on the structure of the prototype agonist ligand, morphine, although N-[methyl-¹¹C]morphine, -codeine and -heroin did not show significant binding in vivo. [¹¹C]Diprenorphine ([¹¹C]DPN), an orvinol type, non-selective OR antagonist ligand, was among the first successful PET tracers for molecular brain imaging, but has been largely supplanted in research studies by the μ-preferring agonist [¹¹C]carfentanil ([¹¹C]Caf). These two tracers have the property of being displaceable by endogenous opioid peptides in living brain, thus potentially serving in a competition-binding model. Indeed, many clinical PET studies with [¹¹C]DPN or [¹¹C]Caf affirm the release of endogenous opioids in response to painful stimuli. Numerous other PET studies implicate μ-OR signaling in aspects of human personality and vulnerability to drug dependence, but there have been very few clinical PET studies of μORs in neurological disorders. Tracers based on naltrindole, a non-peptide antagonist of the δ-preferring endogenous opioid enkephalin, have been used in PET studies of δORs, and [¹¹C]GR103545 is validated for studies of κORs. Structures such as [¹¹C]NOP-1A show selective binding at ORL-1 receptors in living brain. However, there is scant documentation of δ-, κ-, or ORL1 receptors in healthy human brain or in neurological and psychiatric disorders; here, clinical PET research must catch up with recent progress in radiopharmaceutical chemistry. Full article

(This article belongs to the Special Issue Radiolabelled Molecules for Brain Imaging with PET and SPECT)

► Show Figures

Figure 1

Other

Jump to: Research, Review

10 pages, 2212 KiB

Open AccessBrief Report

A New Positron Emission Tomography Probe for Orexin Receptors Neuroimaging

by Ping Bai, Sha Bai, Michael S. Placzek, Xiaoxia Lu, Stephanie A. Fiedler, Brenda Ntaganda, Hsiao-Ying Wey and Changning Wang

Molecules 2020, 25(5), 1018; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules25051018 - 25 Feb 2020

Cited by 10 | Viewed by 3412

Abstract

The orexin receptor (OX) is critically involved in motivation and sleep−wake regulation and holds promising therapeutic potential in various mood disorders. To further investigate the role of orexin receptors (OXRs) in the living human brain and to evaluate the treatment potential of orexin-targeting therapeutics, we herein report a novel PET probe ([¹¹C]CW24) for OXRs in the brain. CW24 has moderate binding affinity for OXRs (IC₅₀ = 0.253 μM and 1.406 μM for OX₁R and OX₂R, respectively) and shows good selectivity to OXRs over 40 other central nervous system (CNS) targets. [¹¹C]CW24 has high brain uptake in rodents and nonhuman primates, suitable metabolic stability, and appropriate distribution and pharmacokinetics for brain positron emission tomography (PET) imaging. [¹¹C]CW24 warrants further evaluation as a PET imaging probe of OXRs in the brain. Full article

(This article belongs to the Special Issue Radiolabelled Molecules for Brain Imaging with PET and SPECT)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Radiolabelled Molecules for Brain Imaging with PET and SPECT

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (11 papers)

Research

Review

Other

Further Information

Guidelines

MDPI Initiatives

Follow MDPI