Special Issue "New Challenges in Radiochemistry"

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (31 August 2016).

Special Issue Editor

Dr. Michel Monclus
E-Mail Website
Guest Editor
PET/Biomedical Cyclotron Unit and Department of Nuclear Medicine, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
Interests: organic synthesis; medicinal chemistry; radiochemistry; automated synthesis

Special Issue Information

Dear Colleagues,

It was in 1930 that E.O. Lawrence developed the first particle accelerator and revolutionized the scientific world.  Since then, this technology has allowed science to make considerable progress in the understanding of matter and the universe (LHC, CERN).

The use of a cyclotron provides access to a variety of synthetic radioisotopes. These were first used for therapeutic applications in medicine. Then, the chemistry of metal–ligand complexes has allowed the development of imaging in nuclear medicine. Finally, more recently, the use of positron emitting radionuclides in relation with the coming of Positron Emission Tomography (PET). The use of compounds labeled with dedicated radioactive tracers made it possible to explore another dimension of nuclear medicine imaging: That of the observation of the functioning of organs in living beings dynamically, non-invasively and without physiological effects. All this would not have been possible without all the dramatic improvements in chemical synthesis strategies acquired these past thirty years.

The aim of this Special Issue of Pharmaceuticals is to report a review of the state of the art of radiochemistry. What are the impacts on new drugs, medical diagnoses, and treatment monitoring of diseases?

Dr. Michel Monclus
Guest Editor

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 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
  • positron
  • imaging
  • radiolabelling
  • automated synthesis
  • radiopharmaceutic

Published Papers (3 papers)

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Research

Open AccessCommunication
Design and Prototype of an Automated Column-Switching HPLC System for Radiometabolite Analysis
Pharmaceuticals 2016, 9(3), 51; https://doi.org/10.3390/ph9030051 - 17 Aug 2016
Cited by 2
Abstract
Column-switching high performance liquid chromatography (HPLC) is extensively used for the critical analysis of radiolabeled ligands and their metabolites in plasma. However, the lack of streamlined apparatus and consequently varying protocols remain as a challenge among positron emission tomography laboratories. We report here [...] Read more.
Column-switching high performance liquid chromatography (HPLC) is extensively used for the critical analysis of radiolabeled ligands and their metabolites in plasma. However, the lack of streamlined apparatus and consequently varying protocols remain as a challenge among positron emission tomography laboratories. We report here the prototype apparatus and implementation of a fully automated and simplified column-switching procedure to allow for the easy and automated determination of radioligands and their metabolites in up to 5 mL of plasma. The system has been used with conventional UV and coincidence radiation detectors, as well as with a single quadrupole mass spectrometer. Full article
(This article belongs to the Special Issue New Challenges in Radiochemistry)
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Open AccessArticle
Feasibility of Multiple Examinations Using 68Ga-Labelled Collagelin Analogues: Organ Distribution in Rat for Extrapolation to Human Organ and Whole-Body Radiation Dosimetry
Pharmaceuticals 2016, 9(2), 31; https://doi.org/10.3390/ph9020031 - 06 Jun 2016
Cited by 5
Abstract
Objectives: Fibrosis is involved in many chronic diseases. It affects the functionality of vital organs, such as liver, lung, heart and kidney. Two novel imaging agents for positron emission tomography (PET) imaging of fibrosis have previously pre-clinically demonstrated promising target binding and [...] Read more.
Objectives: Fibrosis is involved in many chronic diseases. It affects the functionality of vital organs, such as liver, lung, heart and kidney. Two novel imaging agents for positron emission tomography (PET) imaging of fibrosis have previously pre-clinically demonstrated promising target binding and organ distribution characteristics. However, the relevant disease monitoring in the clinical setup would require multiple repetitive examinations per year. Thus, it is of paramount importance to investigate the absorbed doses and total effective doses and thus, the potential maximum number of examinations per year. Methods: Two cyclic peptide (c[CPGRVMHGLHLGDDEGPC]) analogues coupled via an ethylene glycol linker (EG2) to either 2-(4,7-bis(2-(tert-butoxy)-2-oxoethyl)-1,4,7-triazonan-1-yl)acetic acid (NO2A-Col) or 4-(4,7-bis(2-(tert-butoxy)-2-oxoethyl)-1,4,7-triazacyclononan-1-yl)-5-(tert-butoxy)-5-oxopentanoic acid (NODAGA-Col) were labelled with 68Ga. The resulting agents, [68Ga]Ga-NO2A-Col and [68Ga]Ga-NODAGA-Col, were administered in the tail vein of male and female Sprague–Dawley rats (N = 24). An ex vivo organ distribution study was performed at the 5-, 10-, 20-, 40-, 60- and 120-min time points. The resulting data were extrapolated for the estimation of human organ and total body absorbed and total effective doses using Organ Level Internal Dose Assessment Code software (OLINDA/EXM 1.1) assuming a similar organ distribution pattern between the species. Time-integrated radioactivity in each organ was calculated by trapezoidal integration followed by a single-exponential fit to the data points extrapolated to infinity. The resulting values were used for the residence time calculation. Results: Ex vivo organ distribution data revealed fast blood clearance and washout from most of the organs. Although the highest organ absorbed dose was found for kidneys (0.1 mGy/MBq), this organ was not the dose-limiting one and would allow for the administration of over 1460 MBq per year for both [68Ga]Ga-NO2A-Col and [68Ga]Ga-NODAGA-Col. The total effective dose was the limiting parameter with 0.0155/0.0156 (female/male) mSv/MBq and 0.0164/0.0158 (female/male) mSv/MBq, respectively, for [68Ga]Ga-NO2A-Col and [68Ga]Ga-NODAGA-Col. This corresponded to the total amount of radioactivity that could be administered per year of 643 and 621 MBq before reaching the annual limit of 10 mSv. Thus, up to six examinations would be possible. The residence time and organ absorbed doses in liver and spleen were higher for [68Ga]Ga-NODAGA-Col as compared to [68Ga]Ga-NO2A-Col. Conclusion: The limiting parameter for the administered dose was the total effective dose that would allow for at least six examinations per year that might be sufficient for adequate disease monitoring in longitudinal studies and a routine clinical setup. Full article
(This article belongs to the Special Issue New Challenges in Radiochemistry)
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Open AccessArticle
Development of a New Radiofluorinated Quinoline Analog for PET Imaging of Phosphodiesterase 5 (PDE5) in Brain
Pharmaceuticals 2016, 9(2), 22; https://doi.org/10.3390/ph9020022 - 21 Apr 2016
Cited by 7
Abstract
Phosphodiesterases (PDEs) are enzymes that play a major role in cell signalling by hydrolysing the secondary messengers cyclic adenosine monophosphate (cAMP) and/or cyclic guanosine monophosphate (cGMP) throughout the body and brain. Altered cyclic nucleotide-mediated signalling has been associated with a wide array of [...] Read more.
Phosphodiesterases (PDEs) are enzymes that play a major role in cell signalling by hydrolysing the secondary messengers cyclic adenosine monophosphate (cAMP) and/or cyclic guanosine monophosphate (cGMP) throughout the body and brain. Altered cyclic nucleotide-mediated signalling has been associated with a wide array of disorders, including neurodegenerative disorders. Recently, PDE5 has been shown to be involved in neurodegenerative disorders such as Alzheimer’s disease, but its precise role has not been elucidated yet. To visualize and quantify the expression of this enzyme in brain, we developed a radiotracer for specific PET imaging of PDE5. A quinoline-based lead compound has been structurally modified resulting in the fluoroethoxymethyl derivative ICF24027 with high inhibitory activity towards PDE5 (IC50 = 1.86 nM). Radiolabelling with fluorine-18 was performed by a one-step nucleophilic substitution reaction using a tosylate precursor (RCY(EOB) = 12.9% ± 1.8%; RCP > 99%; SA(EOS) = 70–126 GBq/μmol). In vitro autoradiographic studies of [18F]ICF24027 on different mouse tissue as well as on porcine brain slices demonstrated a moderate specific binding to PDE5. In vivo studies in mice revealed that [18F]ICF24027 was metabolized under formation of brain penetrable radiometabolites making the radiotracer unsuitable for PET imaging of PDE5 in brain. Full article
(This article belongs to the Special Issue New Challenges in Radiochemistry)
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