Introduction to the National Cancer Imaging Translational Accelerator (NCITA): a UK-wide infrastructure for multicentre clinical translation of cancer imaging biomarkers

Summary: The National Cancer Imaging Translational Accelerator (NCITA) is creating a UK national coordinated infrastructure for accelerated translation of imaging biomarkers for clinical use. Through the development of standardised protocols, data integration tools and ongoing training programmes, NCITA provides a unique scalable infrastructure for imaging biomarker qualification using multicentre clinical studies

Diet selection and live-weight changes of two breeds of goats grazing on heathlands

Diet selection, live-weight changes and productivity per hectare of two breeds of goats (Cashmere and local Celtiberic) managed in natural vegetation dominated by heather, and the effect of stocking rate (high or low) in the Cashmere breed, were studied during four grazing seasons. Breed had a significant (P , 0.01) effect on the available biomass and its components over the experimental period as a consequence of the differences in dietary components selected by the animals. Local goats produced a greater reduction in short and tall heather and in the percentage of leaves in the tall heather. Live-weight changes were significantly (P , 0.001) different between breeds. Over all experimental years Cashmere goats maintained weight under both low and high stocking rate (4 and 21 g/day respectively), while local Celtiberic goats lost 30 g/day. Across all grazing seasons and experimental years stocking rate did not significantly affect individual live-weight changes of Cashmere goats. Productivity per hectare did not differ significantly (P . 0.05) between high (20.6 kg/ha) and low stocking rate treatments (4.1 kg/ha). However it was significantly (P , 0.001) worse for the local breed treatment (251 kg/ha). As a consequence, in these vegetation communities with low abundance and poor quality of herbaceous plants it will be impossible to develop sustainable systems from the animal production point of view, and their management would need to be integrated during the grazing season by alternating with vegetation communities with better quality

An overview of nuclear medicine research in the UK and the landscape for clinical adoption

Background and objectives Nuclear medicine contributes greatly to the clinical management of patients and experimental medicine. This report aims to (1) outline the current landscape of nuclear medicine research in the UK, including current facilities and recent or ongoing clinical studies and (2) provide information about the available pathways for clinical adoption and NHS funding (commissioning) of radiopharmaceuticals. Methods Evidence was obtained through database searches for UK-based nuclear medicine clinical studies and by conducting a questionnaire-based survey of UK radiopharmaceutical production facilities. A recent history of clinical commissioning, either through recommendations from the National Institute for Health and Care Excellence (NICE) or through NHS specialised services commissioning, was compiled from publicly available documents and policies. Results The collected data highlighted the UK’s active nuclear medicine research community and recent investment in new facilities and upgrades. All commissioning routes favour radiopharmaceuticals that have marketing authorisation and since 2017 there has been a requirement to demonstrate both clinical and cost-effectiveness. Whilst radiopharmaceuticals for molecular radiotherapy are well suited to these commissioning pathways, diagnostic radiotracers have not historically been assessed in this manner. Conclusions We hope that by collating this information we will provide stimulus for future discussion and consensus statements around this topic

Radiation dosimetry and biodistribution in non-human primates of the sodium/iodide PET ligand [¹⁸F]-tetrafluoroborate

Background: [F-18]-tetrafluoroborate is a PET radiotracer taken up by the sodium/iodide symporter (NIS). Albeit the in vivo behavior in rodents is similar to the (99)mTc-pertechnetate, no studies exist in primates or in humans. The aims of this study were to evaluate the biodistribution of [F-18]-tetrafluoroborate in non-human primates with PET and to estimate the absorbed dose in organs. Methods: Whole-body PET imaging was done in a Siemens ECAT HR+ scanner in two male Macaca fascicularis monkeys. After an i.v. injection of 24.93 +/- 0.05 MBq/kg of [F-18]-tetrafluoroborate, prepared by isotopic exchange of sodium tetrafluoroborate with [F-18]-fluoride under acidic conditions, eight sequential images from the head to the thigh (five beds) were collected for a total duration of 132 min. The whole-body emission scan was reconstructed applying attenuation and scatter corrections. After image reconstruction, three-dimensional volumes of interest (VOIs) were hand-drawn on the PET transaxial or coronal slices of the frame where the organ was most conspicuous. Time-activity curves for each VOI were obtained, and the organ residence times were calculated by integration of the time-activity curves. Human absorbed doses were estimated using the OLINDA/EXM software and the standard human model. Results: [F-18]-tetrafluoroborate was able to discriminate clearly the thyroid gland with an excellent signal-to-noise ratio. Most of the radiotracers (residence time) are localised in the organs that express NIS (stomach wall, salivary glands, thyroid, olfactory mucosa), are involved in excretion (kidneys and bladder), or reflect the vascular phase (heart and lungs). Considering the OLINDA source organs, the critical organs were the stomach wall, thyroid and bladder wall, with absorbed doses lower than 0.078 mGy/MBq. The effective dose was 0.025 mSv/MBq. Conclusions: [F-18]-tetrafluoroborate is a very useful radiotracer for PET thyroid imaging in primates, with a characteristic biodistribution in organs expressing NIS. It delivers an effective dose slightly higher than the dose produced by (99)mTc-pertechnetate but much lower than that produced by radioiodine in the form of (INa)-I-131, (INa)-I-123, or (INa)-I-124.MJO acknowledges support from the EPSRC (Life Sciences Interface Fellowship).S

[¹⁸F]tetrafluoroborate-PET/CT enables sensitive tumor and metastasis in vivo imaging in a sodium iodide symporter-expressing tumor model

Cancer cell metastasis is responsible for most cancer deaths. Non-invasive in vivo cancer cell tracking in spontaneously metastasizing tumor models still poses a challenge requiring highest sensitivity and excellent contrast. The goal of this study was to evaluate if the recently introduced PET radiotracer [(18)F]tetrafluoroborate ([(18)F]BF4(-)) is useful for sensitive and specific metastasis detection in an orthotopic xenograft breast cancer model expressing the human sodium iodide symporter (NIS) as a reporter. In vivo imaging was complemented by ex vivo fluorescence microscopy and γ-counting of harvested tissues. Radionuclide imaging with [(18)F]BF4(-) (PET/CT) was compared to the conventional tracer [(123)I]iodide (sequential SPECT/CT). We found that [(18)F]BF4(-) was superior due to better pharmacokinetics, i.e. faster tumor uptake and faster and more complete clearance from circulation. [(18)F]BF4(-)-PET was also highly specific as in all detected tissues cancer cell presence was confirmed microscopically. Undetected comparable tissues were similarly found to be free of metastasis. Metastasis detection by routine metabolic imaging with [(18)F]FDG-PET failed due to low standard uptake values and low contrast caused by adjacent metabolically active organs in this model. [(18)F]BF4(-)-PET combined with NIS expressing disease models is particularly useful whenever preclinical in vivo cell tracking is of interest

Clinical translation of quantitative magnetic resonance imaging biomarkers - An overview and gap analysis of current practice

PURPOSE: This overview of the current landscape of quantitative magnetic resonance imaging biomarkers (qMR IBs) aims to support the standardisation of academic IBs to assist their translation to clinical practice. METHODS: We used three complementary approaches to investigate qMR IB use and quality management practices within the UK: 1) a literature search of qMR and quality management terms during 2011-2015 and 2016-2020; 2) a database search for clinical research studies using qMR IBs during 2016-2020; and 3) a survey to ascertain the current availability and quality management practices for clinical MRI scanners and associated equipment at research institutions across the UK. RESULTS: The analysis showed increased use of all qMR methods between the periods 2011-2015 and 2016-2020 and diffusion-tensor MRI and volumetry to be popular methods. However, the "translation ratio" of journal articles to clinical research studies was higher for qMR methods that have evidence of clinical translation via a commercial route, such as fat fraction and T2 mapping. The number of journal articles citing quality management terms doubled between the periods 2011-2015 and 2016-2020; although, its proportion relative to all journal articles only increased by 3.0%. The survey suggested that quality assurance (QA) and quality control (QC) of data acquisition procedures are under-reported in the literature and that QA/QC of acquired data/data analysis are under-developed and lack consistency between institutions. CONCLUSIONS: We summarise current attempts to standardise and translate qMR IBs, and conclude by outlining the ideal quality management practices and providing a gap analysis between current practice and a metrological standard

Clinical Translation of Quantitative Magnetic Resonance Imaging Biomarkers – an Overview and Gap Analysis of Current Practice

PURPOSE: This overview of the current landscape of quantitative magnetic resonance imaging biomarkers (qMR IBs) aims to support the standardisation of academic IBs to assist their translation to clinical practice. METHODS: We used three complementary approaches to investigate qMR IB use and quality management practices within the UK: 1) a literature search of qMR and quality management terms during 2011-2015 and 2016-2020; 2) a database search for clinical research studies using qMR IBs during 2016-2020; and 3) a survey to ascertain the current availability and quality management practices for clinical MRI scanners and associated equipment at research institutions across the UK. RESULTS: The analysis showed increased use of all qMR methods between the periods 2011-2015 and 2016-2020 and diffusion-tensor MRI and volumetry to be popular methods. However, the "translation ratio" of journal articles to clinical research studies was higher for qMR methods that have evidence of clinical translation via a commercial route, such as fat fraction and T2 mapping. The number of journal articles citing quality management terms doubled between the periods 2011-2015 and 2016-2020; although, its proportion relative to all journal articles only increased by 3.0%. The survey suggested that quality assurance (QA) and quality control (QC) of data acquisition procedures are under-reported in the literature and that QA/QC of acquired data/data analysis are under-developed and lack consistency between institutions. CONCLUSIONS: We summarise current attempts to standardise and translate qMR IBs, and conclude by outlining the ideal quality management practices and providing a gap analysis between current practice and a metrological standard

Additional file 1: of Radiation dosimetry and biodistribution in non-human primates of the sodium/iodide PET ligand [18F]-tetrafluoroborate

3D video of dynamic [18F]-tetrafluoroborate biodistribution. (MOV 776 kb