EH 2_2015

Source:Shutterstock/TylerOlson EUROPEAN HOSPITAL Vol 24 Issue 2/15 12 LABORATORY Figure. A: Protein expression in U87. CD4 tumours as compared to U87.CD4. CXCR4 tumours, as evaluated by western blot (upper CXCR4 middle CD4 and lower β-actin). B: whole body T-2-weighted MR image of mouse after injection of 0.75 mg Fe/kg of pre-aggregated targeted nanoparticles directly into the tumour (tumour area highlighted in red). C & D: Whole body T-2-weighted images of a mouse before (C) and 4 h (D) after the injection of 7.5 mg Fe/Kg of targeted nanoparticles. Red arrows indicate signal loss in the liver and spleen due to accumulation of iron from the nanoparticles. Cancer diagnostics Human resources New nanoparticle could enhance MRI scanning A pathology workforce fit for the future Scientists in the UK have designed a new self-assembling nanoparticle that targets tumours and could lead to quicker diagnosis of cancer, Mark Nicholls reports Researchers at Imperial College London report that a new self- assembling nanoparticle can adhere to cancer cells, thus making them visible in MRI scans and possibly eliminate the need for invasive tis- sue biopsies. The nanoparticle increases the sensitivity and improves the effi- cacy of MRI scanning by ‘specifi- cally seeking out receptors found in cancerous cells’ – a breakthrough the research team suggests has the potential to alter anatomic pathol- ogy’s role in diagnosing cancer and improve doctor’s ability to detect cancerous cells at much earlier stag- es of development. Work is now under way to enhance the effectiveness of the newly designed nanoparticle as a tool to improve the sensitivity of MRI scanning, with a goal to test the design in a human trial within three to five years. Under the process, the nanopar- ticle is coated with a protein that Report: Mark Nicholls The UK pathology sector faces numerous challenges as it strives to create a future medical laboratory workforce. As in many divisions of the National Health Service (NHS), this area has an ageing population yet must evolve against a back- drop of fast-developing technolo- gies, emerging science, financial constraints and the challenge of working in tandem with the private sector. Neil Anderson, Clinical Director of Coventry and Warwickshire Pathology Services, highlighted how UK laboratory medicine is at a pivotal point. He is concerned that the ageing workforce profile could present a problem in the future. ‘Pathology,’ he explained, ‘has an age profile that is tending to show the greatest number of staff in the 40-60-year-old category with not enough staff coming in at the 20-30-year-old category.’ While work has been conduct- ed around workforce patterns, he suggested predictions were often flawed in the way they looked at simply replacing numbers, rather than analysing what type of work- force will be needed in the future. It is about putting the right peo- ple with relevant skills in the posts available and in the right numbers, Anderson said. His concerns centre on a potential de-skilling of the pathology workforce with recruit- ment of more medical laboratory assistants in lower grade pay bands at the expense or experienced staff. ‘That is not just due to budget pressures and cost improvement targets, but also to the fact that to run complex machinery actually requires a range of staff who have different roles. ‘Loading and unloading machines are perhaps jobs more suited to lower staff grade and that could be perceived as a down-skilling, when we desperately need to up-skill staff, especially around the clinical interface, assays selection, interpre- tation and user engagement. We haven’t created the roles we need to respond to future challenges.’ Anderson believes a critical step in meeting those challenges lies with pathology becoming an ‘inte- grated medical service’ rather than being regarded as a support service, and establishing links with commu- nity and acute pathology sectors as it strives to provide ‘more appropri- ate test selection and usage’. ‘In addition, pathology in the United Kingdom needs to become a more coherent business function, needing to understand its costs and have a pricing strategy, articulate visions and, if required, work with the private sector.’ He also feels public sector pathol- ogy needs to be good in areas in which the private sector excels, e.g. managing transition and change, and negotiating discounts with diag- nostic suppliers. One significant development is the 100,000 Genomes Project, which will sequence 100,000 whole genomes from NHS patients by 2017, set up a genomic medicine service for the NHS, enable new scientific discovery and medical insights and kick start the develop- ment of a UK genomics industry. ‘The staff needed to support that are very different to those currently in place within most pathology labora- tories,’ he pointed out. ‘It’s not just about working towards the 100,000 Genome Project, it’s what’s done with those data that emerge from the 100,000 genome project, identification of new companion diagnostic tests, whether in cancer services or endo- crinology and about developing those assays and turning those data into information. ‘The amount of data is rising exponentially and we’re going to work to assimilate that to create information of value to patient care.’ Coventry and Warwick, one of the largest pathology organisations within the UK, is leading the way as it invests in the adoption of digi- tal histopathology and molecular diagnostics to support cellular tech- nology and virology, and is part of an international trial looking at the verification of using digital histopa- thology in a routine setting. ‘We are aware of the implica- tions of the 100,000 genome pro- ject, the implications around rapid diagnostics through point of care testing and its applicability and we are engaged in transforming the way we deliver pathology,’ he said. ‘However, with increased demands on future staffing, we may have to look at alternative models, so that we can adopt new technologies more rapidly.’ Anderson also stressed that, to create a laboratory medicine work- force fit for the future, pathology needs to develop new service mod- els, integrate into clinical teams, embrace specialist working and ulti- mately ensure the appropriate use of pathology. looks for specific signals given off by tumours, and when a tumour is found it begins to interact with the cancerous cells. This interac- tion strips off the protein coating, causing the nanoparticle to self- assemble into a much larger particle so that it is more visible on the scan. For the study, the ICL team used cancer cells and mouse models to compare the effects of the self- assembling nanoparticle in MRI scanning against commonly used imaging agents and found that the nanoparticle produced a more pow- erful signal and created a clearer MRI image of the tumour. Professor Nicholas Long, at the Department of Chemistry at Imperial College London, said the results show real promise for better cancer diagnosis. ‘By improving the sensi- tivity of an MRI examination, our aim is to help doctors spot some- thing that might be cancerous much more quickly,’ he explained. ‘This would enable patients to receive effective treatment sooner, which would hopefully improve survival rates from cancer.’ ‘MRI scanners are found in nearly every hospital and are vital machines used every day to scan patients’ bodies and get to the bot- tom of what might be wrong; but we are aware that some doctors feel that, even though MRI scanners are effective at spotting large tumours, they are perhaps not as good at detecting smaller tumours in the early stages.’ The aim is to improve the design so that doctors can more easily spot a tumour and surgeons can then operate on it. Long: ‘We’re now try- ing to add an extra optical signal, so that the nanoparticle would light up with a luminescent probe once it had found its target, so combined with the better MRI signal this will make it even easier to identify tumours.’ The next research stage will endeavour to fine-tune the size of the final nanoparticle, to be even smaller but still produce an enhanced MRI image. However, researchers are aware that, if the nanoparticle is too small, the body will secrete it before imaging, but if too big it could be harmful. ‘Getting it just right is really important before moving to a human trial,’ added Dr Juan Gallo from the Department of Surgery and Cancer at ICL. * Research funding came from Cancer Research UK, Engineering and Physical Sciences Research Council (EPSRC), the Medical Research Council (MRC) and the Department of Health. Professor Nicholas Long is the Sir Edward Frankland BP Chair in Inorganic Chemistry and Head of the Catalysis, Sustainability and Applied Inorganics Research Section at Imperial College London. The Long Group has expertise in applied synthetic inorganic and organometallic chemistry and his research interests focus on transition metal and lanthanide chemistry for the synthesis of functional molecules, homogeneous catalysis and, in recent years, probe design and novel methodologies for biomedical imaging. He has published c. 150 papers, several high impact review articles and the critically acclaimed textbook, Metallocenes. He received the 2006 RSC Prize in Organometallic Chemistry, was a Leverhulme Trust Research Fellow 2009/10 and, in 2011, became a Fellow of the Royal Society of Chemistry. Neil Anderson is Clinical Director of Coventry and Warwickshire Pathology Services and a consultant clinical biochemist. He addressed the Frontiers in Laboratory Medicine conference earlier this year in the ‘Developing a laboratory medicine workforce fit for the future’ session, when he examined how, given new and emerging technologies, modernising science careers and an ageing workforce, the evolving laboratory workforce can be fit for purpose today and in future.

EH 2_2015

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