ORCID Profile
0000-0003-0099-4984
Current Organisation
Liverpool Hospital
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Publisher: Wiley
Date: 09-11-2021
Publisher: Wiley
Date: 13-01-2021
Publisher: Elsevier BV
Date: 05-2021
DOI: 10.1016/J.NUCMEDBIO.2021.03.011
Abstract: The deuterium labelling of pharmaceuticals is a useful strategy for altering pharmacokinetic properties, particularly for improving metabolic resistance. The pharmacological effects of such metabolites are often assumed to be negligible during standard drug discovery and are factored in later at the clinical phases of development, where the risks and benefits of the treatment and side-effects can be wholly assessed. This paradigm does not translate to the discovery of radiopharmaceuticals, however, as the confounding effects of radiometabolites can inevitably show in preliminary positron emission tomography (PET) scans and thus complicate interpretation. Consequently, the formation of radiometabolites is crucial to take into consideration, compared to non-radioactive metabolites, and the application of deuterium labelling is a particularly attractive approach to minimise radiometabolite formation. Herein, we provide a comprehensive overview of the deuterated carbon-11 and fluorine-18 radiopharmaceuticals employed in PET imaging experiments. Specifically, we explore six categories of deuterated radiopharmaceuticals used to investigate the activities of monoamine oxygenase (MAO), choline, translocator protein (TSPO), vesicular monoamine transporter 2 (VMAT2), neurotransmission and the diagnosis of Alzheimer's disease from which we derive four prominent deuteration strategies giving rise to a kinetic isotope effect (KIE) for reducing the rate of metabolism. Synthetic approaches for over thirty of these deuterated radiopharmaceuticals are discussed from the perspective of deuterium and radioisotope incorporation, alongside an evaluation of the deuterium labelling and radiolabelling efficacies across these independent studies. Clinical and manufacturing implications are also discussed to provide a more comprehensive overview of how deuterated radiopharmaceuticals may be introduced to routine practice.
Publisher: Wiley
Date: 09-05-2019
Abstract: Fluorine-18 is the most utilized radioisotope in positron emission tomography (PET), but the wide application of fluorine-18 radiopharmaceuticals is hindered by its challenging labelling conditions. As such, many potentially important radiotracers remain underutilized. Herein, we describe the use of [
Publisher: CSIRO Publishing
Date: 2019
DOI: 10.1071/CH18512
Abstract: Conjugations with the recently developed [18F]ethenesulfonyl fluoride ([18F]ESF) were performed on 5-amino-1,10-phenanthroline, in its free form and coordinated to a rhenium(i) tricarbonyl complex, as a means of radiosynthesizing dual-modal optical and positron emission tomography (PET) tracers. The Michael-donating ability of the aromatic amine was noticeably perturbed on coordination with the rhenium(i) centre, resulting in decreased radiochemical yields from 34%, in the case of the free ligand, to 1%. We attribute the decreased nucleophilicity of the amine to metal deactivation from the electron-withdrawing feature of the rhenium(i) tricarbonyl centre, based on spectroscopic and computational evidence, thus highlighting this effect as a crucial parameter in designing late-stage metal coordination methods employing related aza-Michael additions. Photophysical analyses were also performed on the ESF-conjugated rhenium(i) complex, exhibiting a longer decay lifetime from the triplet metal-to-ligand charge transfer excited state when compared with the non-conjugated analogue.
Publisher: Wiley
Date: 24-09-2020
Publisher: Wiley
Date: 12-07-2018
DOI: 10.1002/JLCR.3667
Abstract: Fluorine-18 labelled prosthetic groups (PGs) are often necessary for radiolabelling sensitive biological molecules such as peptides and proteins. Several shortcomings, however, often diminish the final yield of radiotracer. In an attempt to provide higher yielding and operationally efficient tools for radiolabelling biological molecules, we describe herein the first radiochemical synthesis of [
Publisher: Wiley
Date: 11-04-2017
Abstract: Azeotropic distillation is typically required to achieve fluorine-18 radiolabeling during the production of positron emission tomography (PET) imaging agents. However, this time-consuming process also limits fluorine-18 incorporation, due to radioactive decay of the isotope and its adsorption to the drying vessel. In addressing these limitations, the fluorine-18 radiolabeling of one model rhenium(I) complex is reported here, which is significantly improved under conditions that do not require azeotropic drying. This work could open a route towards the investigation of a simplified metal-mediated late-stage radiofluorination method, which would expand upon the accessibility of new PET and PET-optical probes.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0RA00318B
Abstract: A novel fluorine-18 radiolabelling method employing rhenium( i ) mediation is described herein. In less than 1 minute, fluorine-18 labelled complexes and ligands were synthesised in greater than 80% and 60% radiochemical yields (RCY), respectively.
Publisher: American Chemical Society (ACS)
Date: 19-06-2020
Publisher: Bentham Science Publishers Ltd.
Date: 12-2023
DOI: 10.2174/1874471016666230502140224
Abstract: During the development of novel Re-188 radiopharmaceuticals, it was discovered that no calibration settings were published to calibrate Re-188 on the Capintec CRC-25PET dose calibrator. Sodium [188Re]perrhenate was eluted from an OncoBeta 188W/188Re generator to measure activity on a Capintec CRC-25R dose calibrator using established dose calibrator settings provided by the manufacturer. The eluent was then used to tune the calibra on settings on a Capintec CRC-25PET dose calibrator, accounting for geometry. Radionuclidic purity of the [188Re]perrhenate source was verified via gamma spectroscopy. The calibrator number for Re-188 was determined to be 469 x 10 for the Capintec CRC-25PET dose calibrator, which differed from the manufacturer provided calibra on number of 496 x 10 for the Capintec CRC-25R dose calibra on model. W-188 breakthrough was characterised as 0.01%. This previously unreported calibration number can be used to determine the activity of Re- 188 labelled radiopharmaceuticals using the Capintec CRC-25PET dose calibrator model.
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0PY00690D
Abstract: Decagram scale syntheses of deuterated mineral oil (d-MO) and poly(1-decene) (d-PD) were achieved by direct catalytic hydrothermal H/D exchange reaction in D 2 O.
Location: Australia
No related grants have been discovered for Mitchell Klenner.