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Radiolabelled Molecules for Brain Imaging with PET and SPECT II

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

Deadline for manuscript submissions: closed (1 June 2021) | Viewed by 10881

Special Issue Editor


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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
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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 diseases, movement and motor disorders, epilepsy, 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, as already outlined in the recently completed Volume I of this Special Issue, 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 Volume II of this Special Issue related to the development and preclinical as well as clinical use of radiolabeled molecules for brain imaging.

Prof. Dr. Peter Brust
Guest Editor

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Keywords

  • PET
  • SPECT
  • Carbon-11
  • Fluorine-18
  • Radiolabelled iodine
  • Technetium-99m
  • Gallium-64
  • Blood–brain barrier
  • Alzheimer’s disease
  • Parkinson’s disease
  • Huntington’s disease
  • Multiple sclerosis
  • Epilepsy
  • Depression
  • Schizophrenia
  • Brain cancer
  • Glioblastoma

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Published Papers (3 papers)

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Research

10 pages, 604 KiB  
Article
Clinical Relevance of [18F]Florbetaben and [18F]FDG PET/CT Imaging on the Management of Patients with Dementia
by Damiano Librizzi, Nicole Cabanel, Maxim Zavorotnyy, Elisabeth Riehl, Tilo Kircher, Markus Luster and Behrooz Hooshyar Yousefi
Molecules 2021, 26(5), 1282; https://doi.org/10.3390/molecules26051282 - 26 Feb 2021
Cited by 5 | Viewed by 3459
Abstract
PET of β-Amyloid plaques (Aβ) using [18F]florbetaben ([18F]FBB) and [18F]fluorodeoxyglucose ([18F]FDG) increasingly aid clinicians in early diagnosis of dementia, including Alzheimer’s disease (AD), frontotemporal disease, dementia with Lewy bodies, and vascular dementia. The aim of [...] Read more.
PET of β-Amyloid plaques (Aβ) using [18F]florbetaben ([18F]FBB) and [18F]fluorodeoxyglucose ([18F]FDG) increasingly aid clinicians in early diagnosis of dementia, including Alzheimer’s disease (AD), frontotemporal disease, dementia with Lewy bodies, and vascular dementia. The aim of this retrospective analysis was to evaluate clinical relevance of [18F]FBB, [18F]FDG PET and complimentary CSF measurements in patients with suspected dementia. In this study, 40 patients with clinically suspected or history of dementia underwent (1) measurement of Aβ peptides, total tau, and p-tau protein levels in the cerebrospinal fluid (CSF) compared with healthy controls (HC); (2) clinical and neuropsychological assessment, which included Consortium to Establish a Registry for Alzheimer’s Disease neuropsychological assessment battery (CERAD-NAB); (3) [18F]FBB and [18F]FDG PET imaging within an average of 3 weeks. The subjects were within 15 days stratified using PET, CSF measurements as HC, mild cognitive impaired (MCI) and dementia including Alzheimer´s disease. The predictive dementia-related cognitive decline values were supporting the measurements. PET images were evaluated visually and quantitatively using standard uptake value ratios (SUVR). Twenty-one (52.5%) subjects were amyloid-positive (Aβ+), with a median neocortical SUVR of 1.80 for AD versus 1.20 relative to the respective 19 (47.5 %) amyloid-negative (Aβ-) subjects. Moreover, the [18F]FDG and [18F]FBB confirmed within a sub-group of 10 patients a good complimentary role by correlation between amyloid pathology and brain glucose metabolism in 8 out of 10 subjects. The results suggest the clinical relevance for [18F]FBB combined with [18F]FDG PET retention and CFS measurements serving the management of our patients with dementia. Therefore, [18F]FBB combined with [18F]FDG PET is a helpful tool for differential diagnosis, and supports the patients’ management as well as treatment. Full article
(This article belongs to the Special Issue Radiolabelled Molecules for Brain Imaging with PET and SPECT II)
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14 pages, 1496 KiB  
Communication
Newly Synthesized Fluorinated Cinnamylpiperazines Possessing Low In Vitro MAO-B Binding
by Ivana I. Jevtić, Thu Hang Lai, Jelena Z. Penjišević, Sladjana Dukić-Stefanović, Deana B. Andrić, Peter Brust, Sladjana V. Kostić-Rajačić and Rodrigo Teodoro
Molecules 2020, 25(21), 4941; https://doi.org/10.3390/molecules25214941 - 26 Oct 2020
Cited by 5 | Viewed by 3401
Abstract
Herein, we report on the synthesis and pharmacological evaluation of ten novel fluorinated cinnamylpiperazines as potential monoamine oxidase B (MAO-B) ligands. The designed derivatives consist of either cinnamyl or 2-fluorocinnamyl moieties connected to 2-fluoropyridylpiperazines. The three-step synthesis starting from commercially available piperazine afforded [...] Read more.
Herein, we report on the synthesis and pharmacological evaluation of ten novel fluorinated cinnamylpiperazines as potential monoamine oxidase B (MAO-B) ligands. The designed derivatives consist of either cinnamyl or 2-fluorocinnamyl moieties connected to 2-fluoropyridylpiperazines. The three-step synthesis starting from commercially available piperazine afforded the final products in overall yields between 9% and 29%. An in vitro competitive binding assay using l-[3H]Deprenyl as radioligand was developed and the MAO-B binding affinities of the synthesized derivatives were assessed. Docking studies revealed that the compounds 817 were stabilized in both MAO-B entrance and substrate cavities, thus resembling the binding pose of l-Deprenyl. Although our results revealed that the novel fluorinated cinnamylpiperazines 817 do not possess sufficient MAO-B binding affinity to be eligible as positron emission tomography (PET) agents, the herein developed binding assay and the insights gained within our docking studies will certainly pave the way for further development of MAO-B ligands. Full article
(This article belongs to the Special Issue Radiolabelled Molecules for Brain Imaging with PET and SPECT II)
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17 pages, 3607 KiB  
Article
Classification of the Multiple Stages of Parkinson’s Disease by a Deep Convolution Neural Network Based on 99mTc-TRODAT-1 SPECT Images
by Shih-Yen Hsu, Li-Ren Yeh, Tai-Been Chen, Wei-Chang Du, Yung-Hui Huang, Wen-Hung Twan, Ming-Chia Lin, Yun-Hsuan Hsu, Yi-Chen Wu and Huei-Yung Chen
Molecules 2020, 25(20), 4792; https://doi.org/10.3390/molecules25204792 - 19 Oct 2020
Cited by 24 | Viewed by 3376
Abstract
Single photon emission computed tomography (SPECT) has been employed to detect Parkinson’s disease (PD). However, analysis of the SPECT PD images was mostly based on the region of interest (ROI) approach. Due to limited size of the ROI, especially in the multi-stage classification [...] Read more.
Single photon emission computed tomography (SPECT) has been employed to detect Parkinson’s disease (PD). However, analysis of the SPECT PD images was mostly based on the region of interest (ROI) approach. Due to limited size of the ROI, especially in the multi-stage classification of PD, this study utilizes deep learning methods to establish a multiple stages classification model of PD. In the retrospective study, the 99mTc-TRODAT-1 was used for brain SPECT imaging. A total of 202 cases were collected, and five slices were selected for analysis from each subject. The total number of images was thus 1010. According to the Hoehn and Yahr Scale standards, all the cases were divided into healthy, early, middle, late four stages, and HYS I~V six stages. Deep learning is compared with five convolutional neural networks (CNNs). The input images included grayscale and pseudo color of two types. The training and validation sets were 70% and 30%. The accuracy, recall, precision, F-score, and Kappa values were used to evaluate the models’ performance. The best accuracy of the models based on grayscale and color images in four and six stages were 0.83 (AlexNet), 0.85 (VGG), 0.78 (DenseNet) and 0.78 (DenseNet). Full article
(This article belongs to the Special Issue Radiolabelled Molecules for Brain Imaging with PET and SPECT II)
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