Sean L. Kitson

Sean L. Kitson
Almac · Biocatalysis and Isotope Chemistry

BSc, PhD, MSc, PGDipMedPhys

About

64
Publications
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272
Citations
Introduction
My present position is an Investigator of Radiochemistry in the Department of Biocatalysis and Isotope Chemistry at Almac, Northern Ireland, UK. Before then Senior Radiochemist in the Custom Labelling Special Synthesis Team at GE Healthcare (formally Amersham). My research interests includes radiolabelling of biomolecules such as antibody drug conjugates (ADCs) and peptides including isotopic labelling of small molecules which can be utilized in ADME studies.
Additional affiliations
September 2008 - present
Almac
Position
  • Investigator of Radiochemistry
Description
  • Synthesis of carbon-14 Labelled API
September 2002 - August 2008
Cytiva
Position
  • Senior Radiochemist
Description
  • Synthesis of Carbon-14 Labelled Compounds
April 2002 - September 2002
Molecular Metaphors
Position
  • Managing Director
Description
  • A new approach to rational drug design using the principles of molecular metaphors

Publications

Publications (64)
Article
Full-text available
Molecular Metaphors is the application of squaryl building blocks towards creative functional group chemistry to produce lead compounds and imaging agents. This strategy is applied to rational drug design and to various imaging agents that would normally contain conventional functional group chemistry. These, include carboxylic acids, α-amino acids...
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Immunotherapies especially targeted towards oncology, based on antibody-drug conjugates (ADCs) have recently been boosted by the US Food and Drug Administration approval of Adcetris to treat Hodgkin’s lymphoma and Kadcyla for metastatic breast cancer. The emphasis of this article is to provide an overview of the design of ADCs in order to examine t...
Article
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Targeted alpha therapy (TAT) is an investigational procedure which utilises monoclonal antibodies (mAbs), peptide conjugates and/or other chemical compounds. These bio-vectors are able to transport a dose of alpha particles to destroy cancer cells. Radionuclide antibody-conjugates (RACs), labelled with beta emitters, have already been used in human...
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This paper will outline the mechanism of the Bischler–Napieralski cyclodehydration for the radiosynthesis of (R)-(-)-[6a-14C]apomorphine 1. The carbon-14 radiosynthesis of (R)-(-)-[6a-14C]apomorphine was first reported by Kitson and Knagg in May 2006. The Bischler–Napieralski cyclodehydration of 3,4-dimethoxy-2-nitrophenyl-N-phenethyl[carboxyl-14C]...
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Positron Emission Tomography (PET) is a diagnostic imaging procedure used regularly to acquire essential clinical information. The PET-CT hybrid, which consists of two scanning machines: PET scanner and an x-ray Computed Tomography (CT). At present these represent the technological hierarchy of Nuclear Medicine, occupying an important position in d...
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Preface The peer-reviewed journal 'Current Radiopharmaceuticals' builds on its success from the previous 13 issues. The journal offers a range of article formats, including research articles, reviews, communications, editorial letters and perspectives. The journal also compiles thematic 'Hot Topic' issues to generate the maximum impact of the publi...
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The first issue of 2020 contains thematic articles on the clinical and prognostic value of diagnostic imaging techniques in melanoma, with the main reference to the role of nuclear medicine, for which, the fields of actual application and perspectives are individuated. Therefore, starting from the clinical value of 18F-FDG-PET/CT in staging and res...
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Preface The peer-reviewed journal 'Current Radiopharmaceuticals' continues to build on its success from the previous eleven issues. The journal offers a range of article formats including research articles, reviews, communications, editorial letters and perspectives. The first issue of 2019 contains articles on PET imaging of small cell lung cancer...
Article
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Background Nephrotoxicity is a prevalentconsequence caused by cancer treatment using radiotherapy and chemotherapy, ortheir combination.There are two methods; histological and biochemical, to assess the kidney damage caused by toxic agents in animal studies. Although, these methods are used for the tryout of renoprotective factors, but these method...
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Carbon‐14 (14C) labelled active pharmaceutical ingredients (APIs) and investigational medicinal products (IMPs) are required for Phase 0/I to Phase III mass balance and micro‐dosing clinical trials. In some cases, this may involve the synthesis of 14C‐labelled peptides and the analysis can be performed by accelerated mass spectroscopy (AMS). The 14...
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The peer-reviewed journal ‘Current Radiopharmaceuticals’ continues to build on its success from the previous ten issues. The journal offers a range of article formats including research articles, reviews, communications, editorial letters and perspectives. The first issue of 2018 contained articles on PET/CT imaging of prostate cancer using the rad...
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Background: Para-18F-fluorohippuric acid (18F-PFH) and ortho-124I-iodohippuric acid (124IOIH) were recently identified as potential radiotracers suitable for conducting renography using positron emission tomography (PET). The aim of this work was to estimate preliminary human-equivalent internal radiation dose of 18F-PFH and 124I-OIH using the bio...
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In the ever-changing, technology-driven pharmaceutical industry, carbon-14 labeling remains “hot” and is still the first-choice technology for labeling active pharmaceutical ingredients (APIs) and their metabolites. Labeling is a critical technology for APIs and allows quantitative information to be gathered on adsorption, distribution, metabolism...
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Full-text available
The peer-reviewed journal ‘Current Radiopharmaceuticals’ continues to build on its success from previous years. The journal offers a range of article formats including research articles, reviews, communications, editorial letters and perspectives. The 2016 issues contained articles on the use of radiopharmaceuticals in imaging to drug discovery and...
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Radionuclide antibody conjugates (RACs) and antibody-drug conjugates (ADCs) can function as biotherapeutic missiles in order to target cancer cells and destroy them. The advent of new technology platforms consisting of imaging modalities, drug design and radiochemistry will facilitate the personalised approach for cancer patient treatment programme...
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Radionuclide antibody conjugates (RACs) and antibody-drug conjugates (ADCs) can function as biotherapeutic missiles in order to target cancer cells and destroy them. The advent of new technology platforms consisting of imaging modalities, drug design and radiochemistry will facilitate the personalised approach for cancer patient treatment programme...
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This manuscript is a complementary article to an accompanying paper, published in a forthcoming issue, which will give an overview on the central role of chelation in labelling radiocompounds; either for imaging and/or for radionuclide therapy. In order to facilitate a better understanding of the importance of Chelator-Based Imaging & Therapy, we w...
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The automated radiosynthesis of [18F]fluorocholine was carried out using a modified reactor design in the GE TracerLab FX(FDG) module. This PET imaging tracer was synthesized in two steps and involved the generation of nucleophilic [18F]fluoride using Kryptofix 2.2.2 technology. The first step was the synthesis of [18F]fluorobromomethane by the rea...
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The success of a drug candidate to reach the market requires a rigorous investigation into its toxicological profile. Therefore, ADME (Absorption, Distribution, Metabolism and Excretion) studies must be executed at an early stage in the clinical development of the investigational drug. The data obtained from these metabolism studies will enable a d...
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Since the conception of the journal Current Radiopharmaceuticals in January 2008, we have been inundated with a variety of research articles ranging from discussions on the use of radiopharmaceuticals in imaging to drug discovery and targeted therapies. All these articles have been peer reviewed by members of editorial board including guest editors...
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Radionuclide therapy and antibody-drug conjugates are used to locate and kill cancer cells by the utilisation of monoclonal antibodies. These bio-vectors are able to transport a cytotoxic drug payload and/or radiation in the form of alpha or beta particles to bind onto antigen specific cancer cells initiating apoptosis. This inaugural article aims...
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Positron Emission Tomography (PET) is a powerful imaging technique exploring in vivo brain functions. Today PET is becoming an essential tool in specialist clinical neurology settings particularly for diagnosing Alzheimer’s, Parkinson’s and epilepsy disease states. This inaugural article aims to deliver a brief insight into PET techniques in the di...
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Abstract Guided by a specific monoclonal antibody (mAb), antibody drug conjugates or ADC are a new, emerging, class of drugs able to deliver a drug payload directly to an intended target. This approach has recently been boosted by the U.S. Food and Drug Administration approval of brentuximab vedotin (Adcetris®; Seattle Genetics) to treat Hodgkin’s...
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Isotopic labelling of APIs is becoming more challenging, particularly for complex targeted therapies. The application of biocatalytic tools can introduce complex functionality in a single step and reduce the cost of developing labelled biomolecules and chiral compounds.
Article
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Immunotherapies especially targeted towards oncology, based on antibody-drug conjugates (ADCs) have recently been boosted by the US Food and Drug Administration approval of Adcetris to treat Hodgkin's lymphoma and Kadcyla for metastatic breast cancer. The emphasis of this article is to provide an overview of the design of ADCs in order to examine t...
Article
Full-text available
The next blockbuster drug revenue streams are likely to come from a class of targeted therapies geared towards the treatment and management of chronic human disease states—especially cancer—and involve the use of antibody-drug conjugates (ADCs).1 A wide range of monoclonal antibodies (mAb) have already been approved by the FDA and includes six engi...
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The authors explain how the synergy between peptide and protein technology and radiolabeling groups can enable the manufacture of carbon-14 labeled peptides and antibody-drug conjugates.
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drug entering the body undergoes a series of biotransformations via phase I and phase II metabolic pathways. During phase I, enzymatic processes in the liver and other tissues introduce reactive or polar (e.g. hydroxyl, thiol, amino, and carboxylic acid) groups, changing the compound’s chemical structure. These biotransformations make the drug more...
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Carbon-14 labelled API and IMP requirements for Phase 0/I to Phase III mass balance, and micro-dosing clinical trials can be met by contract manufacturing in compliance with MHRA and FDA Phase I cGMP guidelines. The short supply and escalating price of carbon-14 labelled building blocks has emphasised the demand for robust synthetic methodologies t...
Article
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Carbon-14 labelled API and IMP requirements for Phase 0/1 to Phase III mass balance and micro-dosing clinical trials can be met by contract manufacturing in compliance with MHRA and FDA Phase I cGMP guidelines. The short supply and escalating price of carbon-14 labelled building blocks has emphasised the demand for robust synthetic methodologies to...
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A drug entering the human body will undergo a series of biotransformations to render it more water-soluble, but the metabolites produced by these processes may be more pharmacologically active at the therapeutic receptor sites than the parent drug. Safety assessments rely primarily on data generated during animal studies, but the metabolite profile...
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Elucidation of the mechanism of formation of two major impurities in the synthetic route towards key intermediate ethyl 5-cyano-2-methyl-6-oxo-1,6-dihydropyridine-3-carboxylate 1, led directly to the development of a route with significant process improvements in terms of yield, purity, and operability. The overall process yield increased from 15%...
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Radiolabelling using 14C is used for assessing the ADME profile of new peptide-based active pharmaceutical ingredients. The label is placed within the core of the drug, avoiding the risk of wash out or the need for a modified structure. The limitation of its modest maximum specific activity can be overcome through the use of Accelerated Mass Spectr...
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The 20th annual symposium of the International Isotope Society's United Kingdom Group took place at the Wellcome Genome Campus, Hinxton, Cambridge, UK on Tuesday 18 October 2011. The meeting was attended by around 70 delegates from academia and industry, the life sciences, chemical, radiochemical and scientific instrument suppliers. Delegates were...
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A method has been developed for the synthesis of two isotopically labelled forms of a pro-drug of the acetylcholinesterase inhibitor (À)-huperzine A. These labelled compounds, [ 14 C]ZT-1 (Debio-9902) and [d 3 ]ZT-1, were used in clinical studies to evaluate a potential treatment for Alzheimer's disease. The pro-drug [ 14 C]ZT-1 was isolated with a...
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Biocatalysis in the pharmaceutical and fine chemical industries continues to grow as it moves from the domain of specialised technology to mainstream methodology, a move that has been facilitated by the increasing commercial "off-the-shelf" availability of biocatalysts at large scale. For example, nitrilase (NIT) biocatalysts have found numerous ap...
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The 19th annual symposium of the International Isotope Society's United Kingdom Group took place at the Wellcome Genome Campus, Hinxton, Cambridge, UK on Thursday 14th October 2010. The meeting was attended by around 80 delegates from academia and industry, the life sciences, chemical, radiochemical and scientific instrument suppliers. Delegates we...
Article
The 19th annual symposium of the International Isotope Society’s United Kingdom Group took place at the Wellcome Genome Campus, Hinxton, Cambridge, UK on Thursday 14th October 2010. The meeting was attended by around 80 delegates from academia and industry, the life sciences, chemical, radiochemical and scientific instrument suppliers. The Harrowve...
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Excellence can be achieved through synergies between synthetic organic chemistry, key technologies and cGMP, explains Sean L Kitson at Almac Pharma companies need to meet radiolabelling requirements in Phase I to Phase III clinical trials. Therefore, cGMP service providers must work closely to generate high quality carbon-14 labelled active pharma...
Article
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A method has been developed for the carbon-14 radiosynthesis of [14C]XEN-D0401, a 4-(2-hydroxyphenyl)quinolin-2(1H)-one derivative. The radiosynthetic route involves a series of ortho-lithiations directed by both 2-methoxymethyl (MOM) and pivaloyl protecting groups. This is demonstrated in the first key radiochemical step between the reaction of 5-...
Article
The protecting group di-(4-methoxyphenyl)methyl, removable by ceric ammonium nitrate on silica or 2,3-dichloro-5,6-dicyanoquinone, is shown to facilitate syntheses of urethanes (eg vinyl urethane, 1a) and uridine derivatives (eg 2-O-allyluridine, 8).
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The first article in this ‘hot topic’ issue of Current Radiopharmaceuticals (Kitson and Mansi et al.) presents a short review of the most important clinical applications of Positron Emission Tomography (PET) in Nuclear Medicine. In particular, emphasis is placed on the use of [18F]fluorodeoxyglucose (FDG) in tumor imaging as this tracer is predomin...
Article
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Serotonin (5-HT) receptors are part of the G protein-coupled and ligand-gated ion channel families. 5-HT exerts its diverse actions by binding to cell surface receptors which can be classified into seven distinct families (5-HT, to 5-HT gamma) according to their structural diversity and mode of action. Some of the 5-HT families are comprised of mul...
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I was invited by Professor John R. Jones (University of Surrey) to write a paper to celebrate 50 years of the Journal of Labelled Compounds and Radiopharmaceuticals. The aim of this paper is to outline briefly the history of radiochemistry from The Radiochemical Centre at Amersham in the 1940s to the acquisition by General Electric in 2004 and the...
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This paper outlines three methods for the incorporation of carbon-14 radiolabels into polymers. The first method discussed used the radiolabeled starting material, [1,6-14C]hexamethylenediamine 2. The reaction of 2 with sodium dicyanamide led to a carbon-14 polybiguanide 3 with a wide molecular weight distribution. An improvement to this reaction w...
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The carbon-14 radiolabels in [bisphosphinoethane-1,2-14C]tetrofosmin ligand were readily introduced by reacting 1,2-dibromo[U-14C]ethane with bis(2-ethoxyethyl)benzylphosphine (1). This was converted to the Myoview™ ligand in an overall yield of 45%. This radiosynthesis was important in obtaining marketing approval from the regulatory authorities a...
Article
Full-text available
Serotonin (5-HT) receptors are part of the G protein-coupled and ligand-gated ion channel families. 5-HT exerts its diverse actions by binding to cell surface receptors which can be classified into seven distinct families (5-HT1 to 5-HT7) according to their structural diversity and mode of action. Some of the 5-HT families are comprised of multiple...
Article
Full-text available
A method has been developed for the carbon-14 radiosynthesis of non-narcotic morphine derivative (R)-(-)-[6a-14C]apomorphine (1) from the starting material 3,4-dimethoxy-2-nitrophenyl-N-phenethyl[carboxyl-14C]acetamide (5). The key to this synthesis was the application of the Bischler–Napieralski cyclodehydration to 1-(3,4-dimethoxy-2-nitrobenzyl)d...
Article
Meeting ProgrammeDr Nigel Botting [University of St Andrews, UK] – Isotopic Labelling of Lignan Phytoestrogens.Prof. Frédéric Dollé [CEA PET Centre, Orsay, France] – Fluorine-18 Chemistry: A Selection of Recent Advances.Prof. Peter Scott [University of Warwick, UK] – Creating Chiral Metal Centres.Mr Laurent Brichard [WBIC, University of Cambridge,...
Article
Studies on the chromoprotein antibiotic neocarzinostatinThe ‘special effects’ of microwaving in radiochemistry.Stable isotopes and membrane transport proteins: chemical synthesis and biochemical analysis by solid state NMRSynthetic aspects of c-deuteriation of enolatesOpportunities for isotope labelling via solid phase synthesis with organogermaniu...
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Ethenyl carbamate was obtained by selenoxide fragmentation of 2-phenylselenylethyl carbamate. Base-catalysed exchange of ethyl phenylselenylacetate in methanol-OD gave methyl [2H2]phenylselenylacetate from which [2-2H2]ethenyl carbamate and [2-2H2]oxiranol carbamate were derived. Thermolysis of oxiranol carbamate in eg acetone gave 4-hydroxy-1,3-ox...
Article
Thesis (Ph. D.)--University of Newcastle upon Tyne, 1993.

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