ANSTO :: Browsing by Author "Fraser, BH"

Browsing by Author "Fraser, BH"

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[18F]Ethenesulfonyl fluoride as a practical radiofluoride relay reagent
(John Wiley & Sons, Inc, 2019-04-11) Zhang, B; Fraser, BH; Klenner, MA; Chen, Z; Liang, SH; Massi, M; Robinson, AJ; Pascali, G
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 [18F]ethenesulfonyl fluoride (ESF) as a novel radiofluoride relay reagent that allows radiofluorination reactions to be performed in minimally equipped satellite nuclear medicine centres. [18F]ESF has a simple and reliable production route and can be stored on inert cartridges. The cartridges can then be shipped remotely and the trapped [18F]ESF can be liberated by simple solvent elution. We have tested 18 radiolabelling precursors, inclusive of model and clinically used structures, and most precursors have demonstrated comparable radiofluorination efficiencies to those obtained using a conventionally dried [18F]fluoride source. © 2019 Wiley-VCH Verlag GmbH & Co.
Ascertaining the suitability of aryl sulfonyl fluorides for [18F]radiochemistry applications: a systematic investigation using microfluidics
(American Chemical Society, 2013-10-18) Matesic, L; Wyatt, NA; Fraser, BH; Roberts, MP; Pham, TQ; Greguric, I
Optimization of [18F]radiolabeling conditions and subsequent stability analysis in mobile phase, PBS buffer, and rat serum of 12 aryl sulfonyl chloride precursors with various substituents (electron-withdrawing groups, electron-donating groups, increased steric bulk, heterocyclic) were performed using an Advion NanoTek Microfluidic Synthesis System. A comparison of radiochemical yields and reaction times for a microfluidics device versus a conventional reaction vessel is reported. [18F]Radiolabeling of sulfonyl chlorides in the presence of competing nucleophiles, H-bond donors, and water was also assessed and demonstrated the versatility and potential utility of [18F]sulfonyl fluorides as synthons for indirect radiolabeling. © 2013 American Chemical Society
Astrocytic TSPO upregulation appears before microglial TSPO in Alzheimer’s disease
(IOS Press, 2020-06-30) Tournier, BB; Tsartsalis, S; Ceyzériat, K; Fraser, BH; Grégoire, MC; Kövari, E; Millet, P
Background: In vivo PET/SPECT imaging of neuroinflammation is primarily based on the estimation of the 18 kDa-rranslocator-protein (TSPO). However, TSPO is expressed by different cell types which complicates the interpretation. Objective: The present study evaluates the cellular origin of TSPO alterations in Alzheimer’s disease (AD). Methods: The TSPO cell origin was evaluated by combining radioactive imaging approaches using the TSPO radiotracer [125I]CLINDE and fluorescence-activated cell sorting, in a rat model of AD (TgF344-AD) and in AD subjects. Results: In the hippocampus of TgF344-AD rats, TSPO overexpression not only concerns glial cells but the increase is visible at 12 and 24 months in astrocytes and only at 24 months in microglia. In the temporal cortex of AD subjects, TSPO upregulation involved only glial cells. However, the mechanism of this upregulation appears different with an increase in the number of TSPO binding sites per cell without cell proliferation in the rat, and a microglial cell population expansion with a constant number of binding sites per cell in human AD. Conclusion: These data indicate an earlier astrocyte intervention than microglia and that TSPO in AD probably is an exclusive marker of glial activity without interference from other TSPO-expressing cells. This observation indicates that the interpretation of TSPO imaging depends on the stage of the pathology, and highlights the particular role of astrocytes. © 2020 IOS Press and the authors. Open Access CC BY-NC 4.0
Comparative analysis of novel decynium-22 analogs to inhibit transport by the low-affinity, high-capacity monoamine transporters, organic cation transporters 2 and 3, and plasma membrane monoamine transporter
(Elsevier B. V., 2019-01) Fraser-Spears, R; Krause-Heuer, AM; Basiouny, M; Mayer, FP; Manishimwe, M; Wyatt, NA; Dobrowolski, JC; Roberts, MP; Greguric, I; Kumar, N; Koek, W; Sitte, HH; Callaghan, PD; Fraser, BH; Daws, LC
Growing evidence supports involvement of low-affinity/high-capacity organic cation transporters (OCTs) and plasma membrane monoamine transporter (PMAT) in regulating clearance of monoamines. Currently decynium-22 (D22) is the best pharmacological tool to study these transporters, however it does not readily discriminate among them, underscoring a need to develop compounds with greater selectivity for each of these transporters. We developed seven D22 analogs, and previously reported that some have lower affinity for α1-adrenoceptors than D22 and showed antidepressant-like activity in mice. Here, we extend these findings to determine the affinity of these analogs for OCT2, OCT3 and PMAT, as well as serotonin, norepinephrine and dopamine transporters (SERT, NET and DAT) using a combination of uptake competition with [3H]methyl-4-phenylpyridinium acetate in overexpressed HEK cells and [3H]citalopram, [3H]nisoxetine and [3H]WIN 35428 displacement binding in mouse hippocampal and striatal preparations. Like D22, all analogs showed greater binding affinities for OCT3 than OCT2 and PMAT. However, unlike D22, some analogs also showed modest affinity for SERT and DAT. Dual OCT3/SERT and/or OCT3/DAT actions of certain analogs may help explain their ability to produce antidepressant-like effects in mice and help account for our previous findings that D22 lacks antidepressant-like effects unless SERT function is either genetically or pharmacologically compromised. Though these analogs are not superior than D22 in discriminating among OCTs/PMAT, our findings point to development of compounds with combined ability to inhibit both low-affinity/high-capacity transporters, such as OCT3, and high-affinity/low-capacity transporters, such as SERT, as therapeutics with potentially improved efficacy for treatment of psychiatric disorders. © 2021 Elsevier B.V.
Cutting edge rare earth radiometals: prospects for cancer theranostics
(Springer Nature, 2022-08-26) Sadler, AWE; Hogan, L; Fraser, BH; Rendina, LM
With recent advances in novel approaches to cancer therapy and imaging, the application of theranostic techniques in personalised medicine has emerged as a very promising avenue of research inquiry in recent years. Interest has been directed towards the theranostic potential of Rare Earth radiometals due to their closely related chemical properties which allow for their facile and interchangeable incorporation into identical bifunctional chelators or targeting biomolecules for use in a diverse range of cancer imaging and therapeutic applications without additional modification, i.e. a “one-size-fits-all” approach. This review will focus on recent progress and innovations in the area of Rare Earth radionuclides for theranostic applications by providing a detailed snapshot of their current state of production by means of nuclear reactions, subsequent promising theranostic capabilities in the clinic, as well as a discussion of factors that have impacted upon their progress through the theranostic drug development pipeline. In light of this interest, a great deal of research has also been focussed towards certain under-utilised Rare Earth radionuclides with diverse and favourable decay characteristics which span the broad spectrum of most cancer imaging and therapeutic applications, with potential nuclides suitable for α-therapy (149Tb), β−-therapy (47Sc, 161Tb, 166Ho, 153Sm, 169Er, 149Pm, 143Pr, 170Tm), Auger electron (AE) therapy (161Tb, 135La, 165Er), positron emission tomography (43Sc, 44Sc, 149Tb, 152Tb, 132La, 133La), and single photon emission computed tomography (47Sc, 155Tb, 152Tb, 161Tb, 166Ho, 153Sm, 149Pm, 170Tm). For a number of the aforementioned radionuclides, their progression from ‘bench to bedside’ has been hamstrung by lack of availability due to production and purification methods requiring further optimisation. Conclusions In order to exploit the potential of these radionuclides, reliable and economical production and purification methods that provide the desired radionuclides in high yield and purity are required. With more reactors around the world being decommissioned in future, solutions to radionuclide production issues will likely be found in a greater focus on linear accelerator and cyclotron infrastructure and production methods, as well as mass separation methods. Recent progress towards the optimisation of these and other radionuclide production and purification methods has increased the feasibility of utilising Rare Earth radiometals in both preclinical and clinical settings, thereby placing them at the forefront of radiometals research for cancer theranostics. © 2022 The Author(s) . Open Access under a Creative Commons Attribution 4.0 International License.
Derivatives of imidazotriazine and pyrrolotriazine C-nucleosides as potential new anti-HCV agents
(Elsevier B.V., 2014-11-01) Draffan, AG; Frey, B; Fraser, BH; Pool, B; Gannon, C; Tyndall, EM; Cianci, J; Harding, M; Lilly, M; Hufton, R; Halim, R; Jahangiri, S; Bond, S; Jeynes, TP; Nguyen, VTT; Wirth, V; Luttick, A; Tilmanis, D; Pryor, M; Porter, K; Morton, CJ; Lin, B; Duan, J; Bethell, RC; Kukojl, G; Simoneau, B; Tucker, SP
Previous investigations identified 2′-C-Me-branched ribo-C-nucleoside adenosine analogues, 1, which contains a pyrrolo[2,1-f][1,2,4]triazin-4-amine heterocyclic base, and 2, which contains an imidazo[2,1-f][1,2,4]triazin-4-amine heterocyclic base as two compounds with promising anti-HCV in vitro activity. This Letter describes the synthesis and evaluation of a series of novel analogues of these compounds substituted at the 2-, 7-, and 8-positions of the heterocyclic bases. A number of active new HCV inhibitors were identified but most compounds also demonstrated unacceptable cytotoxicity. However, the 7-fluoro analogue of 1 displayed good potency with a promising cytotherapeutic margin. © 2014 Elsevier Ltd.
Developing national capability for the production and use of radiometal based radiopharmaceuticals
(John Wiley & Sons, Inc, 2013-04-11) Lengkeek, NA; Pellegrini, PA; Oehlke, E; Fraser, BH; Greguric, I
Radiometals remain key radioisotopes for radio-medicine; the mainstay diagnostic medical imaging isotope, 99mTc, and important radioisotopes for radiotherapy, 90Y and 153Sm. However, the worldwide growth in PET centres, driven by the wildly successful [18F]-FDG, has provided a yet to be seized opportunity to deliver radiometal-based radiopharmaceuticals with clinical relevance to researchers. An ever growing set of radiometals is becoming available in Australia covering a wide range of half-lives, nuclear and chemical properties, these include 64Cu, 68Ga, 86Y, 89Zr, and looking into the near future, 44Sc, 45Ti and 90Nb. ANSTO's Lifesciences division is working to provide the Australian academic and clinical communities access to the following key areas. Radioisotope supply Two in-house 68Ge/68Ga generators; one solely for research and a larger generator for pre-clinical trials, provide access to this key radioisotope. ANSTO has provided financial and technical support to numerous cyclotron centres around Australia for development of solid targetry facilities, ensuring supply of 124I, 64Cu, 86Y and 89Zr in the short-term and 44Sc, 45Ti and 90Nb later. In coming years the OPAL reactor will begin producing pharmaceutical grade 177Lu as part of the Australian government's investment in nuclear medicine. Radiometal Labelling Research and Development In addition to our programs developing new ligands, tracers and improved radiometal labelling procedures, Lifesciences is supporting the development of new biomolecule treatments by providing researchers access to laboratories, procedures and expertise tailored specifically for functionalising biomolecules for radiometal labelling. Preclinical Radiometal Tracer Development We are working to deliver novel radiometal-based diagnostic tracers to the Australian research and clinical community by accessing the pre-clinical programs of our key international partnerships at Memorial Sloan Kettering Cancer Centre and Massachusetts General Hospital. Our initial objective is to supply the antibodies, i.e. [ 89 Zr]-J591. As our supply radiometals is diversified we will expand into proteins, peptides and other biomolecules. © 2013 John Wiley & Sons, Inc.
Development of novel ligands for emerging radiometal isotopes
(John Wiley & Sons, Inc., 2013-04-11) Ashford, ME; Burgess, L; Cheah, WC; Krause-Heuer, AM; Fraser, BH; Greguric, I; Lengkeek, NA
Background: The use of radiometals (non-Tc, non-Re) in targeted diagnosis and radiotherapy of different disease states has increased significantly over the last 15 years. ANSTO LifeSciences radiometals program seeks to provide a suite of radiometal tools for use in PET imaging and therapeutic modalities to improve upon the existing technologies which are currently dominated by 99mTc. This will enable researchers and clinicians to study and diagnose diseases with a greater efficacy and efficiency. Method: Many of the ligands currently available for radiometals have numerous drawbacks , including unfavourable in vivo properties such as thermodynamic and kinetic stability and poor lipophilicity. We are developing new ligand systems to have improved radiometal specificity while including design flexibility allowing us to manipulate properties such as biodistribution patterns, excretion rates, pharmacokinetics, thermodynamics and in vivo stability. The synthesis should be straightforward and cost effective and have the potential for bioconjugation in the initial design. Complexation studies are performed in vitro to assess the ligands suitability. Results: We are developing ligand systems for 68Ga, 89Zr, 64Cu, 90Y and 177Lu. We have prepared a novel analogue of the ubiquitous ligand NOTA (Figure 1, b); our system replaces the biologically labile carboxylic acid with a corresponding, biologically inert isotere, a tetrazole. This manipulation should provide additional stability and increased complex lipophilicity. Our studies have shown that a tetrazole analogue of NOTA (Figure 1, b) forms stable cold-metal complexes with potential PET metals of interest such as Ga3+. Conclusion: ANSTO LifeSciences provides a complete synthetic ligand and metal complex program, complementing its broader Radiometals Program. The aim of which is to provide an array of clinically relevant ligands that can be used in multiple applications for specific metal radiopharmaceuticals for improved patient outcomes. © 2013 John Wiley & Sons
Differential activity of decynium-22 analogs: novel targets for probing low-affinity/high-capacity biogenic amine transporters
(Federation of American Societies for Experimental Biology (FASEB), 2015-04-01) Fraser, R; Owens, A; Wyatt, NA; Krause-Heuer, AM; Greguric, I; Callaghan, PD; Fraser, BH; Daws, LC
We study neurotransmitter clearance by low-affinity, high-capacity uptake-2 transporters. This family includes plasma membrane monoamine transporter (PMAT) and three organic cation transporter isoforms (OCT1-3). We have shown uptake-2 transporters limit the effectiveness of the selective serotonin reuptake inhibitor (SSRI) fluvoxamine. Discerning the transporter type(s) involved is restricted by the lack of highly selective ligands. This project examines the pharmacological characteristics of novel uptake-2 compounds. Activity of ANSTO analogs, structurally based on the non-selective inhibitor decynium 22 (D22), was tested in human OCT3-HEK cells. Ligand competitions of [3H]MPP+ uptake were measured in whole, attached cells. Compared to D22, dose-responses of ANSTO compounds shifted 1- or 2 log-rightward, indicating reduced potency to inhibit OCT3 mediated [3H]MPP+ uptake. ANSTO analogs displayed similar potencies to corticosterone and may have higher selectivity at alternate uptake 2 subtypes. © 2015 Federation of American Societies for Experimental Biology (FASEB)
Effect of rhenium(i) complexation on aza-Michael additions to 5-amino-1,10-phenanthroline with [18F]ethenesulfonyl fluoride towards PET optical tracer development
(CSIRO Publishing, 2019-01-14) Klenner, MA; Pascali, G; Zhang, B; Ciancaleoni, G; Massi, M; Fraser, BH
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. © CSIRO 1996-2021
Efficient access to chromeno[4,3-b]quinolines related to dependensin
(© Georg Thieme Verlag Stuttgart, 2017-08-08) Dobrowolski, JC; Fraser, BH; Bhadbhade, MM; Black, DS; Kumar, N
We report a robust synthesis of novel chromeno[4,3-b]quinoline derivatives structurally similar to the natural product dependensin. The target compounds are accessed through the acid-catalysed condensation of 2-aminoacetophenones or 2-aminochalcones with substituted flavanones, which are in turn obtained from 2-hydroxyacetophenones and benzaldehydes. © 2017 Georg Thieme Verlag Stuttgart
Evaluation of the antidepressant therapeutic potential of isocyanine and pseudoisocyanine analogues of the organic cation decynium-22
(Elsevier B. V., 2017-09-08) Krause-Heuer, AM; Fraser-Spears, R; Dobrowolski, JC; Ashford, ME; Wyatt, NA; Roberts, MP; Gould, GG; Cheah, WC; Ng, CKL; Bhadbhade, MM; Zhang, B; Greguric, I; Wheate, NJ; Kumar, N; Koek, W; Callaghan, PD; Daws, LC; Fraser, BH
Antidepressant-like activity Herein we describe the synthesis and evaluation of antidepressant properties of seven analogues (1–7) of the low affinity/high capacity transporter blocker decynium-22 (D-22). All analogues (1–7) were synthesized via base promoted coupling reactions between N-alkylated-2-methylquinolinium iodides or N-alkylated-4-methylquinolinium iodides and electrophilic N-alkylated-2-iodoquinolinium iodides. All final compounds were purified by re-crystallization or preparative HPLC and initial evaluation studies included; 1) screening for in vitro α1-adrenoceptor activity (a property that can lead to unwanted side-effects), 2) measuring antidepressant-like activity in a mouse tail suspension test (TST), and 3) measuring effects upon mouse locomotion. The results showed some analogues have lower affinities at α1-adrenoceptors compared to D-22 and showed antidepressant-like activity without the need for co-administration of SSRIs. Additionally, many analogues did not affect mouse locomotion to the same extent as D-22. Plans for additional evaluations of these promising analogues, including measurement of antidepressant-like activity with co-administration of selective serotonin re-uptake inhibitors (SSRIs), are outlined. © 2017 Elsevier B.V.
Fluorescence-activated cell sorting to reveal the cell origin of radioligand binding
(SAGE, 2019-06-19) Tournier, BB; Tsartsalis, S; Ceyzériat, K; Medina, Z; Fraser, BH; Grégoire, MC; Kövari, E; Millet, P
Many studies have explored the role of TSPO (18 kDa translocator protein) as a marker of neuroinflammation using single-photon emission computed tomography (SPECT) or positron emission tomography (PET). In vivo imaging does not allow to determine the cells in which TSPO is altered. We propose a methodology based on fluorescence-activated cell sorting to sort different cell types of radioligand-treated tissues. We compared left/right hippocampus of rats in response to a unilateral injection of lipopolysaccharide (LPS), ciliary neurotrophic factor (CNTF) or saline. We finally applied this methodology in human samples (Alzheimer's disease patients and controls). Our data show that the pattern of TSPO overexpression differs across animal models of acute neuroinflammation. LPS induces a microglial expansion and an increase in microglial TSPO binding. CNTF is associated with an increase in TSPO binding in microglia and astrocytes in association with an increase in the number of microglial binding sites per cell. In humans, we show that the increase in CLINDE binding in Alzheimer's disease concerns microglia and astrocytes in the presence of a microglial expansion. Thus, the cellular basis of TSPO overexpression is condition dependent, and alterations in TSPO binding found in PET/SPECT imaging studies cannot be attributed to particular cell types indiscriminately. © 2021 International Society for Cerebral Blood Flow and Metabolism
A fluorine-18 radiolabeling method enabled by rhenium(I) complexation circumvents the requirement of anhydrous conditions
(John Wiley & Sons, Inc, 2017-03-22) Klenner, MA; Pascali, G; Zhang, B; Sia, TR; Spare, LK; Krause-Heuer, AM; Aldrich-Wright, JR; Greguric, I; Guastella, AJ; Massi, M; Fraser, BH
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. © 2017 John Wiley & Sons, Inc
Fluorine-18 radiolabelling and in vitro / in vivo metabolism of [18F]D4-PBR111
(John Wiley & Sons, Inc, 2019-05-26) Wyatt, NA; Safavi-Naeini, M; Wotherspoon, ATL; Arthur, A; Nguyen, AP; Parmar, A; Hamze, H; Day, CM; Zahra, D; Matesic, L; Davis, E; Rahardjo, GL; Yepuri, NR; Shepherd, R; Murphy, RB; Pham, TQ; Nguyen, VH; Callaghan, PD; Holden, PJ; Grégoire, MC; Darwish, TA; Fraser, BH
Objectives The purinergic receptor P2X ligand-gated ion channel type 7 (P2X7R) is an adenosine triphosphate (ATP)-gated ion-channel, and P2X7R is a key player in inflammation. P2X7R is an emerging therapeutic target in central nervous system (CNS) diseases including Alzheimer's disease (AD) and Parkinson's disease (PD), because P2X7R also plays a pivotal role in neuroinflammation. P2X7R represents a potential molecular imaging target for neuroinflammation via biomedical imaging technique positron emission tomography (PET), and several radioligands targeting P2X7R have been developed and evaluated in animals. In our previous work, we have developed and characterized [11C]GSK1482160 as a P2X7R radioligand for neuroinflammation,2 clinical evaluation of [11C]GSK1482160 in healthy controls and patients is currently underway, and the estimation of radiation dosimetry for [11C]GSK1482160 in normal human subjects has been reported.3 Since the half-life (t1/2) of radionuclide carbon-11 is only 20.4 min, it is attractive for us to develop derivatives of [11C]GSK1482160, which can be labeled with the radionuclide fluorine-18 (t1/2, 109.7 min), and a fluorine-18 ligand would be ideal for widespread use.4 To this end, a series of [18F]fluoroalkyl including [18F]fluoromethyl (FM), [18F]fluoroethyl (FE), and [18F]fluoropropyl (FP) derivatives of GSK1482160 have been prepared and examined as new potential P2X7R radioligands. © 2019 The Authors
Gd-TPP-DOTA reduces cell viability in cancer cells via synchrotron radiotherapy
(Australian National University, 2021-08-24) Middleton, RJ; Howell, NR; Livio, E; Wyatt, NA; Chacon, A; Fraser, BH; Barnes, M; Cameron, M; Rendina, LM; Häusermann, D; Lerch, M; Safavi-Naeini, M
High-Z elements have been proposed as radiosensitisers in X-ray photon radiotherapy due to their emission of multiple high-LET photo- and Auger electrons following X-ray irradiation. Gadolinium is a particularly attractive candidate radiosensitiser, since it can also be used as an MRI contrast agent. In this study, we report on the efficacy of Gd-triphenylphosphonium salt-DOTA (Gd(III)-TPP-DOTA) for synchrotron microbeam radiation therapy dose enhancement. The compound utilises the mitochondrial targeting moiety triphenylphosphonium (TPP) to accumulate Gd in the inner mitochondrial membrane. Experiments were conducted using the dynamic mode option at hutch 2B of the Imaging and Medical Beamline at the Australian Synchrotron. Human glioblastoma multiforme cells (T98G cell line) were cultured to 80-90% confluence in T12.5 flasks. Approximately 24 hours prior to irradiation, the cultures were either treated with a 500 μM solution of Gd(III)DOTA-TPP or a vehicle control. Spatial dose distribution of synchrotron broad beam (BB) and single/multiple microbeams were measured using a micron-scale X-Tream dosimetry system and Gafchromic films in air and at 2 cm depth in solid water (same depth as the monolayer of cells in T12.5 flasks). A total of 96 flasks were irradiated, with doses of 0, 1, 2, 3, 4, 5, 10 and 16 Gy delivered in valley (MRT) or uniformly (BB). Post irradiation, each flask was re-seeded into 7 x 96 well-plates to perform the resazurin cell proliferation assay up to 7 days after irradiation. Our preliminary analysis indicates that for cells irradiated by 3 Gy of BB or MRT radiation, the addition of Gd(III)DOTA-TPP results in a reduction in viable cell mass by 24.25% and 25.79%, respectively, compared with untreated flasks. © The Authors
A general and efficient synthesis of 5,6-dihydrodibenzo[b,h][1,6]naphthyridine derivatives
(Elsevier B. V., 2016-12-07) Dobrowolski, JC; Katen, A; Fraser, BH; Bhadbhade, MM; Black, DS; Kumar, N
A two-step procedure for the synthesis of dihydrodibenzonaphthyridine derivatives from benzaldehydes and 2-aminoacetophenones, proceeding through a substituted dihydroquinolone intermediate, is described. The synthetic protocol allows for a versatile and robust coupling method between a range of 2-aminoacetophenones or 2-aminobenzophenones and a selection of substituted dihydroquinolones. © 2016 Elsevier B.V.
A general synthesis of 7-Phenyl-7,13-dihydro-8H-benzo[6,7]azepino[3,2-c]quinolin-8-ones
(Thieme, 2019-02-13) Dobrowolski, JC; Nguyen, DHT; Fraser, BH; Bhadbhade, MM; Black, DS; Kumar, N
Complex benzazepinoquinolone scaffolds can be accessed from the reaction of 2-aminoacetophenones and oxindole derivatives and feature the seven-membered azepine ring moiety commonly found in a range of drug molecules. The described reaction is generally applicable and allows for rapid access to a diverse range of new structures with further potential to build more elaborate molecules. © 2021 Georg Thieme Verlag KG
A general synthesis of benzoazepinoindoles – a new class of heterocycles
(Thieme, 2019-10-09) Dobrowolski, JC; Nguyen, DHT; Fraser, BH; Bhadbhade, MM; Black, DS; Kumar, N
A new class of heterocyclic compounds, namely the benzoazepinoindolones, has been synthesised through a base-catalysed cyclisation reaction of 1,4-bis(2-aminophenyl)-2-phenylbutane-1,4-dione derivatives and features the prominent seven-membered azepine ring moiety. This synthesis has considerable scope for the rapid generation of more complex structures and is inexpensive and generally applicable. © 2019 Georg Thieme Verlag
In vivo evaluation of radiofluorinated caspase-3/7 inhibitors as radiotracers for apoptosis imaging and comparison with [18F]ML-10 in a stroke model in the rat
(Springer Nature, 2016-02-01) Médoc, M; Dhilly, M; Matesic, L; Toutain, J; Krause-Heuer, AM; Delamare, J; Fraser, BH; Touzani, O; Barré, L; Greguric, I; Sobrio, F
The first biological evaluation of two potent fluorine-18 radiolabelled inhibitors of caspase-3/7 was achieved in a cerebral stroke rat model to visualize apoptosis © 2016 Springer Nature

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