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Current Aspects of Radiopharmaceutical Chemistry

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

Deadline for manuscript submissions: closed (30 January 2018) | Viewed by 79469

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Special Issue Editor

Prof. Dr. Peter Brust

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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
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue is related to recent developments in the field of radiopharmaceutical chemistry.

Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are in vivo molecular imaging devices which are widely used in nuclear medicine for diagnosis and treatment follow-up of many major diseases. They use biomolecules as probes, which are labeled with radionuclides of short half-lives, synthesized prior to the imaging studies. These probes are called radiopharmaceuticals. Their design and development is a rather interdisciplinary process covering many different disciplines of natural and health sciences. In addition to their diagnostic and therapeutic purposes in the field of nuclear medicine radiopharmaceuticals provide powerful tools for in vivo pharmacology during the process of pre-clinical 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 the field are cordially invited to contribute original research papers or reviews to this Special Issue of Molecules.

Prof. Dr. Peter Brust
Guest Editor

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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

Radiolabelling
Radionuclide generators
Multimodality imaging probes
Carbon-11 chemistry
Fluorine-18 chemistry
Structure-based radiotracer design
Ligand-based radiotracer design
Target validation
Radiotracer metabolism
Neuroimaging
Tumor imaging

Published Papers (12 papers)

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Research

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12 pages, 1687 KiB

Open AccessArticle

Combining Albumin-Binding Properties and Interaction with Pemetrexed to Improve the Tissue Distribution of Radiofolates

by Cristina Müller, Patrycja Guzik, Klaudia Siwowska, Susan Cohrs, Raffaella M. Schmid and Roger Schibli

Molecules 2018, 23(6), 1465; https://doi.org/10.3390/molecules23061465 - 16 Jun 2018

Cited by 8 | Viewed by 3253

Abstract

Folic-acid-based radioconjugates have been developed for nuclear imaging of folate receptor (FR)-positive tumors; however, high renal uptake was unfavorable in view of a therapeutic application. Previously, it was shown that pre-injection of pemetrexed (PMX) increased the tumor-to-kidney ratio of radiofolates several-fold. In this study, PMX was combined with the currently best performing radiofolate ([¹⁷⁷Lu]cm13), which is outfitted with an albumin-binding entity. Biodistribution studies were carried out in mice bearing KB or IGROV-1 tumor xenografts, both FR-positive tumor types. SPECT/CT was performed with control mice injected with [¹⁷⁷Lu]folate only and with mice that received PMX in addition. Control mice showed high uptake of radioactivity in KB and IGROV-1 tumor xenografts, but retention in the kidneys was also high, resulting in tumor-to-kidney ratios of ~0.85 (4 h p.i.) and ~0.60 (24 h p.i.) or ~1.17 (4 h p.i.) and ~1.11 (24 h p.i.) respectively. Pre-injection of PMX improved the tumor-to-kidney ratio to values of ~1.13 (4 h p.i.) and ~0.92 (24 h p.i.) or ~1.79 (4 h p.i.) and ~1.59 (24 h p.i.), respectively, due to reduced uptake in the kidneys. It was found that a second injection of PMX—3 h or 7 h after administration of the radiofolate—improved the tumor-to-kidney ratio further to ~1.03 and ~0.99 or ~1.78 and ~1.62 at 24 h p.i. in KB and IGROV-1 tumor-bearing mice, respectively. SPECT/CT scans readily visualized the tumor xenografts, whereas accumulation of radioactivity in the kidneys was reduced in mice that received PMX. In this study, it was shown that PMX had a positive impact in terms of reducing the kidney uptake of albumin-binding radiofolates; hence, the administration of PMX resulted in ~1.3–1.7-fold higher tumor-to-kidney ratios. This is, however, a rather moderate effect in comparison to the previously shown effect of PMX on conventional radiofolates (without albumin binder), which led to 5–6-fold increased tumor-to-kidney ratios. An explanation for this result may be the different pharmacokinetic profiles of PMX and long-circulating radiofolates, respectively. Despite the promising potential of this concept, it is believed that a clinical translation would be challenging, particularly when PMX had to be injected more than once. Full article

(This article belongs to the Special Issue Current Aspects of Radiopharmaceutical Chemistry)

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16 pages, 4326 KiB

Open AccessArticle

[¹⁸F]FEPPA a TSPO Radioligand: Optimized Radiosynthesis and Evaluation as a PET Radiotracer for Brain Inflammation in a Peripheral LPS-Injected Mouse Model

by Nicolas Vignal, Salvatore Cisternino, Nathalie Rizzo-Padoin, Carine San, Fortune Hontonnou, Thibaut Gelé, Xavier Declèves, Laure Sarda-Mantel and Benoît Hosten

Molecules 2018, 23(6), 1375; https://doi.org/10.3390/molecules23061375 - 07 Jun 2018

Cited by 35 | Viewed by 6431

Abstract

[¹⁸F]FEPPA is a specific ligand for the translocator protein of 18 kDa (TSPO) used as a positron emission tomography (PET) biomarker for glial activation and neuroinflammation. [¹⁸F]FEPPA radiosynthesis was optimized to assess in a mouse model the cerebral inflammation induced by an intraperitoneal injection of Salmonella enterica serovar Typhimurium lipopolysaccharides (LPS; 5 mg/kg) 24 h before PET imaging. [¹⁸F]FEPPA was synthesized by nucleophilic substitution (90 °C, 10 min) with tosylated precursor, followed by improved semi-preparative HPLC purification (retention time 14 min). [¹⁸F]FEPPA radiosynthesis were carried out in 55 min (from EOB). The non-decay corrected radiochemical yield were 34 ± 2% (n = 17), and the radiochemical purity greater than 99%, with a molar activity of 198 ± 125 GBq/µmol at the end of synthesis. Western blot analysis demonstrated a 2.2-fold increase in TSPO brain expression in the LPS treated mice compared to controls. This was consistent with the significant increase of [¹⁸F]FEPPA brain total volume of distribution (V_T) estimated with pharmacokinetic modelling. In conclusion, [¹⁸F]FEPPA radiosynthesis was implemented with high yields. The new purification/formulation with only class 3 solvents is more suitable for in vivo studies. Full article

(This article belongs to the Special Issue Current Aspects of Radiopharmaceutical Chemistry)

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13 pages, 3722 KiB

Open AccessArticle

Bridging from Brain to Tumor Imaging: (S)-(−)- and (R)-(+)-[¹⁸F]Fluspidine for Investigation of Sigma-1 Receptors in Tumor-Bearing Mice

by Mathias Kranz, Ralf Bergmann, Torsten Kniess, Birgit Belter, Christin Neuber, Zhengxin Cai, Gang Deng, Steffen Fischer, Jiangbing Zhou, Yiyun Huang, Peter Brust, Winnie Deuther-Conrad and Jens Pietzsch

Molecules 2018, 23(3), 702; https://doi.org/10.3390/molecules23030702 - 20 Mar 2018

Cited by 7 | Viewed by 5116

Abstract

Sigma-1 receptors (Sig1R) are highly expressed in various human cancer cells and hence imaging of this target with positron emission tomography (PET) can contribute to a better understanding of tumor pathophysiology and support the development of antineoplastic drugs. Two Sig1R-specific radiolabeled enantiomers (S)-(−)- and (R)-(+)-[¹⁸F]fluspidine were investigated in several tumor cell lines including melanoma, squamous cell/epidermoid carcinoma, prostate carcinoma, and glioblastoma. Dynamic PET scans were performed in mice to investigate the suitability of both radiotracers for tumor imaging. The Sig1R expression in the respective tumors was confirmed by Western blot. Rather low radiotracer uptake was found in heterotopically (subcutaneously) implanted tumors. Therefore, a brain tumor model (U87-MG) with orthotopic implantation was chosen to investigate the suitability of the two Sig1R radiotracers for brain tumor imaging. High tumor uptake as well as a favorable tumor-to-background ratio was found. These results suggest that Sig1R PET imaging of brain tumors with [¹⁸F]fluspidine could be possible. Further studies with this tumor model will be performed to confirm specific binding and the integrity of the blood-brain barrier (BBB). Full article

(This article belongs to the Special Issue Current Aspects of Radiopharmaceutical Chemistry)

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8 pages, 1136 KiB

Open AccessArticle

Influence of Storage Temperature on Radiochemical Purity of ^99mTc-Radiopharmaceuticals

by Licia Uccelli, Alessandra Boschi, Petra Martini, Corrado Cittanti, Stefania Bertelli, Doretta Bortolotti, Elena Govoni, Luca Lodi, Simona Romani, Samanta Zaccaria, Elisa Zappaterra, Donatella Farina, Carlotta Rizzo, Melchiore Giganti and Mirco Bartolomei

Molecules 2018, 23(3), 661; https://doi.org/10.3390/molecules23030661 - 15 Mar 2018

Cited by 4 | Viewed by 3918

Abstract

The influence of effective room temperature on the radiochemical purity of ^99mTc-radiopharmaceuticals was reported. This study was born from the observation that in the isolators used for the preparation of the ^99mTc-radiopharmaceuticals the temperatures can be higher than those reported in the commercial illustrative leaflets of the kits. This is due, in particular, to the small size of the work area, the presence of instruments for heating, the continuous activation of air filtration, in addition to the fact that the environment of the isolator used for the ^99mTc-radiopharmaceuticals preparation and storage is completely isolated and not conditioned. A total of 244 ^99mTc-radiopharmaceutical preparations (seven different types) have been tested and the radiochemical purity was checked at the end of preparation and until the expiry time. Moreover, we found that the mean temperature into the isolator was significantly higher than 25 °C, the temperature, in general, required for the preparation and storage of ^99mTc-radiopharmaceuticals. Results confirmed the radiochemical stability of radiopharmaceutical products. However, as required in the field of quality assurance, the impact that different conditions than those required by the manufacturer on the radiopharmaceuticals quality have to be verified before human administration. Full article

(This article belongs to the Special Issue Current Aspects of Radiopharmaceutical Chemistry)

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18 pages, 8808 KiB

Open AccessArticle

[¹⁸F]fallypride-PET/CT Analysis of the Dopamine D₂/D₃ Receptor in the Hemiparkinsonian Rat Brain Following Intrastriatal Botulinum Neurotoxin A Injection

by Teresa Mann, Jens Kurth, Alexander Hawlitschka, Jan Stenzel, Tobias Lindner, Stefan Polei, Alexander Hohn, Bernd J. Krause and Andreas Wree

Molecules 2018, 23(3), 587; https://doi.org/10.3390/molecules23030587 - 06 Mar 2018

Cited by 8 | Viewed by 5376

Abstract

Intrastriatal injection of botulinum neurotoxin A (BoNT-A) results in improved motor behavior of hemiparkinsonian (hemi-PD) rats, an animal model for Parkinson’s disease. The caudate–putamen (CPu), as the main input nucleus of the basal ganglia loop, is fundamentally involved in motor function and directly interacts with the dopaminergic system. To determine receptor-mediated explanations for the BoNT-A effect, we analyzed the dopamine D₂/D₃ receptor (D₂/D₃R) in the CPu of 6-hydroxydopamine (6-OHDA)-induced hemi-PD rats by [¹⁸F]fallypride-PET/CT scans one, three, and six months post-BoNT-A or -sham-BoNT-A injection. Male Wistar rats were assigned to three different groups: controls, sham-injected hemi-PD rats, and BoNT-A-injected hemi-PD rats. Disease-specific motor impairment was verified by apomorphine and amphetamine rotation testing. Animal-specific magnetic resonance imaging was performed for co-registration and anatomical reference. PET quantification was achieved using PMOD software with the simplified reference tissue model 2. Hemi-PD rats exhibited a constant increase of 23% in D₂/D₃R availability in the CPu, which was almost normalized by intrastriatal application of BoNT-A. Importantly, the BoNT-A effect on striatal D₂/D₃R significantly correlated with behavioral results in the apomorphine rotation test. Our results suggest a therapeutic effect of BoNT-A on the impaired motor behavior of hemi-PD rats by reducing interhemispheric changes of striatal D₂/D₃R. Full article

(This article belongs to the Special Issue Current Aspects of Radiopharmaceutical Chemistry)

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15 pages, 1301 KiB

Open AccessArticle

Investigation of an ¹⁸F-labelled Imidazopyridotriazine for Molecular Imaging of Cyclic Nucleotide Phosphodiesterase 2A

by Susann Schröder, Barbara Wenzel, Winnie Deuther-Conrad, Rodrigo Teodoro, Mathias Kranz, Matthias Scheunemann, Ute Egerland, Norbert Höfgen, Detlef Briel, Jörg Steinbach and Peter Brust

Molecules 2018, 23(3), 556; https://doi.org/10.3390/molecules23030556 - 02 Mar 2018

Cited by 8 | Viewed by 4319

Abstract

Specific radioligands for in vivo visualization and quantification of cyclic nucleotide phosphodiesterase 2A (PDE2A) by positron emission tomography (PET) are increasingly gaining interest in brain research. Herein we describe the synthesis, the ¹⁸F-labelling as well as the biological evaluation of our latest PDE2A (radio-)ligand 9-(5-Butoxy-2-fluorophenyl)-2-(2-([¹⁸F])fluoroethoxy)-7-methylimidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine (([¹⁸F])TA5). It is the most potent PDE2A ligand out of our series of imidazopyridotriazine-based derivatives so far (IC₅₀ hPDE2A = 3.0 nM; IC₅₀ hPDE10A > 1000 nM). Radiolabelling was performed in a one-step procedure starting from the corresponding tosylate precursor. In vitro autoradiography on rat and pig brain slices displayed a homogenous and non-specific binding of the radioligand. Investigation of stability in vivo by reversed-phase HPLC (RP-HPLC) and micellar liquid chromatography (MLC) analyses of plasma and brain samples obtained from mice revealed a high fraction of one main radiometabolite. Hence, we concluded that [¹⁸F]TA5 is not appropriate for molecular imaging of PDE2A neither in vitro nor in vivo. Our ongoing work is focusing on further structurally modified compounds with enhanced metabolic stability. Full article

(This article belongs to the Special Issue Current Aspects of Radiopharmaceutical Chemistry)

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15 pages, 3100 KiB

Open AccessArticle

Exploring the Metabolism of (+)-[¹⁸F]Flubatine In Vitro and In Vivo: LC-MS/MS Aided Identification of Radiometabolites in a Clinical PET Study †

by Friedrich-Alexander Ludwig, Steffen Fischer, René Smits, Winnie Deuther-Conrad, Alexander Hoepping, Solveig Tiepolt, Marianne Patt, Osama Sabri and Peter Brust

Molecules 2018, 23(2), 464; https://doi.org/10.3390/molecules23020464 - 20 Feb 2018

Cited by 8 | Viewed by 4682

Abstract

Both (+)-[¹⁸F]flubatine and its enantiomer (−)-[¹⁸F]flubatine are radioligands for the neuroimaging of α4β2 nicotinic acetylcholine receptors (nAChRs) by positron emission tomography (PET). In a clinical study in patients with early Alzheimer’s disease, (+)-[¹⁸F]flubatine ((+)-[¹⁸F]1) was examined regarding its metabolic fate, in particular by identification of degradation products detected in plasma and urine. The investigations included an in vivo study of (+)-flubatine ((+)-1) in pigs and structural elucidation of formed metabolites by LC-MS/MS. Incubations of (+)-1 and (+)-[¹⁸F]1 with human liver microsomes were performed to generate in vitro metabolites, as well as radiometabolites, which enabled an assignment of their structures by comparison of LC-MS/MS and radio-HPLC data. Plasma and urine samples taken after administration of (+)-[¹⁸F]1 in humans were examined by radio-HPLC and, on the basis of results obtained in vitro and in vivo, formed radiometabolites were identified. In pigs, (+)-1 was monohydroxylated at different sites of the azabicyclic ring system of the molecule. Additionally, one intermediate metabolite underwent glucuronidation, as also demonstrated in vitro. In humans, a fraction of 95.9 ± 1.9% (n = 10) of unchanged tracer remained in plasma, 30 min after injection. However, despite the low metabolic degradation, both radiometabolites formed in humans could be characterized as (i) a product of C-hydroxylation at the azabicyclic ring system, and (ii) a glucuronide conjugate of the precedingly-formed N8-hydroxylated (+)-[¹⁸F]1. Full article

(This article belongs to the Special Issue Current Aspects of Radiopharmaceutical Chemistry)

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3761 KiB

Open AccessArticle

Synthesis of ¹¹C-Labelled Ureas by Palladium(II)-Mediated Oxidative Carbonylation

by Sara Roslin, Peter Brandt, Patrik Nordeman, Mats Larhed, Luke R. Odell and Jonas Eriksson

Molecules 2017, 22(10), 1688; https://doi.org/10.3390/molecules22101688 - 10 Oct 2017

Cited by 14 | Viewed by 5465

Abstract

Positron emission tomography is an imaging technique with applications in clinical settings as well as in basic research for the study of biological processes. A PET tracer, a biologically active molecule where a positron-emitting radioisotope such as carbon-11 has been incorporated, is used for the studies. Development of robust methods for incorporation of the radioisotope is therefore of the utmost importance. The urea functional group is present in many biologically active compounds and is thus an attractive target for incorporation of carbon-11 in the form of [¹¹C]carbon monoxide. Starting with amines and [¹¹C]carbon monoxide, both symmetrical and unsymmetrical ¹¹C-labelled ureas were synthesised via a palladium(II)-mediated oxidative carbonylation and obtained in decay-corrected radiochemical yields up to 65%. The added advantage of using [¹¹C]carbon monoxide was shown by the molar activity obtained for an inhibitor of soluble epoxide hydrolase (247 GBq/μmol–319 GBq/μmol). DFT calculations were found to support a reaction mechanism proceeding through an ¹¹C-labelled isocyanate intermediate. Full article

(This article belongs to the Special Issue Current Aspects of Radiopharmaceutical Chemistry)

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Review

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24 pages, 1791 KiB

Open AccessReview

Recent Advances in Zirconium-89 Chelator Development

by Nikunj B. Bhatt, Darpan N. Pandya and Thaddeus J. Wadas

Molecules 2018, 23(3), 638; https://doi.org/10.3390/molecules23030638 - 12 Mar 2018

Cited by 82 | Viewed by 7962

Abstract

The interest in zirconium-89 (⁸⁹Zr) as a positron-emitting radionuclide has grown considerably over the last decade due to its standardized production, long half-life of 78.2 h, favorable decay characteristics for positron emission tomography (PET) imaging and its successful use in a variety of clinical and preclinical applications. However, to be utilized effectively in PET applications it must be stably bound to a targeting ligand, and the most successfully used ⁸⁹Zr chelator is desferrioxamine B (DFO), which is commercially available as the iron chelator Desferal^®. Despite the prevalence of DFO in ⁸⁹Zr-immuno-PET applications, the development of new ligands for this radiometal is an active area of research. This review focuses on recent advances in zirconium-89 chelation chemistry and will highlight the rapidly expanding ligand classes that are under investigation as DFO alternatives. Full article

(This article belongs to the Special Issue Current Aspects of Radiopharmaceutical Chemistry)

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14 pages, 2825 KiB

Open AccessReview

PET Imaging of Microglial Activation—Beyond Targeting TSPO

by Bieneke Janssen, Danielle J. Vugts, Albert D. Windhorst and Robert H. Mach

Molecules 2018, 23(3), 607; https://doi.org/10.3390/molecules23030607 - 08 Mar 2018

Cited by 79 | Viewed by 12666

Abstract

Neuroinflammation, which involves microglial activation, is thought to play a key role in the development and progression of neurodegenerative diseases and other brain pathologies. Positron emission tomography is an ideal imaging technique for studying biochemical processes in vivo, and particularly for studying the living brain. Neuroinflammation has been traditionally studied using radiotracers targeting the translocator protein 18 kDa, but this comes with certain limitations. The current review describes alternative biological targets that have gained interest for the imaging of microglial activation over recent years, such as the cannabinoid receptor type 2, cyclooxygenase-2, the P2X₇ receptor and reactive oxygen species, and some promising radiotracers for these targets. Although many advances have been made in the field of neuroinflammation imaging, current radiotracers all target the pro-inflammatory (M1) phenotype of activated microglia, since the number of known biological targets specific for the anti-inflammatory (M2) phenotype that are also suited as a target for radiotracer development is still limited. Next to proceeding the currently available tracers for M1 microglia into the clinic, the development of a suitable radiotracer for M2 microglia would mean a great advance in the field, as this would allow for imaging of the dynamics of microglial activation in different diseases. Full article

(This article belongs to the Special Issue Current Aspects of Radiopharmaceutical Chemistry)

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18 pages, 2385 KiB

Open AccessReview

Progress in Targeted Alpha-Particle Therapy. What We Learned about Recoils Release from In Vivo Generators

by Ján Kozempel, Olga Mokhodoeva and Martin Vlk

Molecules 2018, 23(3), 581; https://doi.org/10.3390/molecules23030581 - 05 Mar 2018

Cited by 69 | Viewed by 13830

Abstract

This review summarizes recent progress and developments as well as the most important pitfalls in targeted alpha-particle therapy, covering single alpha-particle emitters as well as in vivo alpha-particle generators. It discusses the production of radionuclides like ²¹¹At, ²²³Ra, ²²⁵Ac/²¹³Bi, labelling and delivery employing various targeting vectors (small molecules, chelators for alpha-emitting nuclides and their biomolecular targets as well as nanocarriers), general radiopharmaceutical issues, preclinical studies, and clinical trials including the possibilities of therapy prognosis and follow-up imaging. Special attention is given to the nuclear recoil effect and its impacts on the possible use of alpha emitters for cancer treatment, proper dose estimation, and labelling chemistry. The most recent and important achievements in the development of alpha emitters carrying vectors for preclinical and clinical use are highlighted along with an outlook for future developments. Full article

(This article belongs to the Special Issue Current Aspects of Radiopharmaceutical Chemistry)

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27 pages, 7006 KiB

Open AccessReview

Advances in the Development of PET Ligands Targeting Histone Deacetylases for the Assessment of Neurodegenerative Diseases

by Tetsuro Tago and Jun Toyohara

Molecules 2018, 23(2), 300; https://doi.org/10.3390/molecules23020300 - 31 Jan 2018

Cited by 25 | Viewed by 5330

Abstract

Epigenetic alterations of gene expression have emerged as a key factor in several neurodegenerative diseases. In particular, inhibitors targeting histone deacetylases (HDACs), which are enzymes responsible for deacetylation of histones and other proteins, show therapeutic effects in animal neurodegenerative disease models. However, the details of the interaction between changes in HDAC levels in the brain and disease progression remain unknown. In this review, we focus on recent advances in development of radioligands for HDAC imaging in the brain with positron emission tomography (PET). We summarize the results of radiosynthesis and biological evaluation of the HDAC ligands to identify their successful results and challenges. Since 2006, several small molecules that are radiolabeled with a radioisotope such as carbon-11 or fluorine-18 have been developed and evaluated using various assays including in vitro HDAC binding assays and PET imaging in rodents and non-human primates. Although most compounds do not readily cross the blood-brain barrier, adamantane-conjugated radioligands tend to show good brain uptake. Until now, only one HDAC radioligand has been tested clinically in a brain PET study. Further PET imaging studies to clarify age-related and disease-related changes in HDACs in disease models and humans will increase our understanding of the roles of HDACs in neurodegenerative diseases. Full article

(This article belongs to the Special Issue Current Aspects of Radiopharmaceutical Chemistry)

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