Visualising children’s participation in research: Lego Duplo, rainbows and clouds and moodboards

This article was published in the International Journal of Social Research Methodology [© Taylor & Francis] and the definitive version is available at: http://dx.doi.org/10.1080/13645579.2012.649410This paper examines the use of visual methods during research encounters with children and young people when investigating their perspectives and feelings towards their home and school life. By revealing the advantages and constraints of three visual approaches, including Lego Duplo, rainbows and clouds and moodboards, the paper contributes to the range of techniques available when conducting research with children and young people. In conclusion, the paper highlights the depth of information which can be elicited from visual techniques as well as the oral data which can be obtained through the utilisation of visual methods

Molecular tracers for the PET and SPECT imaging of disease

The development of positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging continues to grow due to the ability of these techniques to allow the non-invasive in vivo visualisation of biological processes at the molecular and cellular levels. As well as finding application for the diagnosis of disease, these techniques have also been used in the drug discovery process. Crucial to the growth of these techniques is the continued development of molecular probes that can bind to the target biological receptor with high selectivity. This tutorial review describes the use of PET and SPECT for molecular imaging and highlights key strategies for the development of molecular probes for the imaging of both cancer and neurological diseases

Novel SPECT receptor ligands for the investigation of dementia.

Abstract not available

Radiotracer properties determined by high performance liquid chromatography: a potential tool for brain radiotracer discovery

Introduction Previously, development of novel brain radiotracers has largely relied on simple screening tools. Improved selection methods at the early stages of radiotracer discovery and an increased understanding of the relationships between in vitro physicochemical and in vivo radiotracer properties are needed. We investigated if high performance liquid chromatography (HPLC) methodologies could provide criteria for lead candidate selection by comparing HPLC measurements with radiotracer properties in humans. Methods Ten molecules, previously used as radiotracers in humans, were analysed to obtain the following measures: partition coefficient (Log P); permeability (Pm); percentage of plasma protein binding (%PPB); and membrane partition coefficient (Km). Relationships between brain entry measurements (Log P, Pm and %PPB) and in vivo brain percentage injected dose (%ID); and Km and specific binding in vivo (BPND) were investigated. Log P values obtained using in silico packages and flask methods were compared with Log P values obtained using HPLC. Results The modelled associations with %ID were stronger for %PPB (r2=0.65) and Pm (r2=0.77) than for Log P (r2=0.47) while 86% of BPND variance was explained by Km. Log P values were variable dependant on the methodology used. Conclusions Log P should not be relied upon as a predictor of blood-brain barrier penetration during brain radiotracer discovery. HPLC measurements of permeability, %PPB and membrane interactions may be potentially useful in predicting in vivo performance and hence allow evaluation and ranking of compound libraries for the selection of lead radiotracer candidates at early stages of radiotracer discover

Nickel-catalysed aromatic Finkelstein reaction of aryl and heteroaryl bromides

A fast and efficient nickel-catalysed iodination reaction of aryl and heteroaryl bromides has been developed. The transformation was found to be general for a wide range of substrates and was used for the synthesis of iodo-PK11195, an imaging agent of Alzheimer's disease and iniparib, a compound used in the treatment of breast cancer

Development of the radiosynthesis of high-specific-activity ¹²³I-NKJ64

<p><b>Introduction:</b> <sup>123</sup>I-NKJ64, a reboxetine analogue, is currently under development as a potential novel single photon emission computed tomography radiotracer for imaging the noradrenaline transporter in brain. This study describes the development of the radiosynthesis of <sup>123</sup>I-NKJ64, highlighting the advantages and disadvantages, pitfalls and solutions encountered while developing the final radiolabelling methodology.</p> <p><b>Methods:</b> The synthesis of <sup>123</sup>I-NKJ64 was evaluated using an electrophilic iododestannylation method, where a Boc-protected trimethylstannyl precursor was radioiodinated using peracetic acid as an oxidant and deprotection was investigated using either trifluoroacetic acid (TFA) or 2 M hydrochloric acid (HCl).</p> <p><b>Results:</b> Radioiodination of the Boc-protected trimethylstannyl precursor was achieved with an incorporation yield of 92±6%. Deprotection with 2 M HCl produced <sup>123</sup>I-NKJ64 with the highest radiochemical yield of 98.05±1.63% compared with 83.95±13.24% with TFA. However, the specific activity of the obtained <sup>123</sup>I-NKJ64 was lower when measured after using 2 M HCl (0.15±0.23 Ci/µmol) as the deprotecting agent in comparison to TFA (1.76±0.60 Ci/µmol). Further investigation of the 2 M HCl methodology found a by-product, identified as the deprotected proto-destannylated precursor, which co-eluted with <sup>123</sup>I-NKJ64 during the high-performance liquid chromatography (HPLC) purification.</p> <p><b>Conclusions:</b> The radiosynthesis of <sup>123</sup>I-NKJ64 was achieved with good isolated radiochemical yield of 68% and a high specific activity of 1.8 Ci/µmol. TFA was found to be the most suitable deprotecting agent, since 2 M HCl generated a by-product that could not be fully separated from <sup>123</sup>I-NKJ64 using the HPLC methodology investigated. This study highlights the importance of HPLC purification and accurate measurement of specific activity while developing new radiosynthesis methodologies.</p&gt

Structure–activity relationships of novel iodinated quinoline-2-carboxamides for targeting the translocator protein

In an effort to develop a new SPECT imaging agent for the translocator protein (TSPO), a series of novel iodinated quinoline-2-carboxamides have been synthesised and evaluated for binding affinity using rat brain homogenates. The outcome of the biological testing in combination with HPLC determination of the physicochemical properties of these compounds directed the design of new analogues resulting in 4-(2-iodophenyl)quinoline-2-N-diethylcarboxamide, a new TSPO ligand with higher affinity than the widely used clinical imaging agent PK11195

Experimental treatment of neuroblastoma using [131I]meta-iodobenzylguanidine and topotecan in combination

The radiopharmaceutical [I-131]meta-iodobenzylguanidine ([I-131]MIBG) and the topoisomerase I inhibitor topotecan are both effective as single-agent treatments of neuroblastoma. Our purpose was to assess the therapeutic potential of [I-131]MIBG and topotecan in combination using SK-N-BE(2c) neuroblastoma cells and UVW/NAT glioma cells expressing the noradrenaline transporter transgene. Topotecan treatment was given (i) before, (ii) after or (iii) simultaneously with [I-131]MIBG. DNA fragmentation was evaluated by comet assay and cell cycle redistribution was determined by fluorescence-activated cell sorting. Combination index analysis indicated that delivery schedules (ii) and (iii) were more effective than schedule (i) with respect to clonogenic cell kill. Similarly, significant DNA damage was observed following treatment schedules (ii) and (iii) (p <0.005), but not (i). Prior exposure to topotecan did not significantly enhance [I-131]MIBG uptake in athymic mice bearing tumour xenografts. We conclude that the enhancement of the efficacy of [I-131]MIBG by combining it with topotecan was the result of inhibition of DNA damage repair rather than an increase in expression of the noradrenaline transporter by tumour

New iodinated quinloine-2-varboxamides for SPECT imaging of the translocator protein

With the aim of developing new SPECT imaging agents for the translocator protein (TSPO), a small library of iodinated quinoline-2-carboxamides have been prepared and tested for binding affinity with TSPO. N,N-Diethyl-3-iodomethyl-4-phenylquinoline-2-carboxamide was found to have excellent affinity (Ki 12.0 nM), comparable to that of the widely used TSPO imaging agent PK11195