Radiation protection aspects for alpha therapies.

The use of alpha emitting radiotherapeutics is increasing, with further growth expected due to a number of clinical trials currently running involving new alpha emitters. However, literature concerning radiation safety aspects of alpha emitting radionuclides is limited and most of the available literature concerns 223Ra. In general, the occupational exposure from alpha emitting radionuclides is expected to be low, as are doses to the public from external exposure. However, care must be taken to avoid skin contamination, inhalation, and ingestion. Not all alpha emitting radionuclides are identical, they often have very different associated decay chains and emissions. The decay chains and the manufacturing process should be carefully examined to identify any long-lived progeny or impurities. These may have an impact on the radiation safety processes required to limit occupational exposure and for waste management. Doses to the public must also be assessed, either arising directly from exposure to patients treated with radiotherapeutics, or via waste streams. Risk assessments should be in place when starting a new service covering all aspects of the preparation and administration, as well as any foreseeable incidents such as skin contamination or patient death, and the appropriate steps to take in these instances. It is imperative that with the increase in the use of alpha emitting radiotherapeutics more literature is published on radiation safety aspects, especially for new alpha emitting radiotherapeutics which often have very different characteristics than the currently established ones.

The effect of carbohydrases or prebiotic oligosaccharides on growth performance, nutrient utilisation and development of small intestine and immune organs in broilers fed nutrient-adequate diets based on either wheat or barley.

BACKGROUND: Non-starch polysaccharides are large complex molecules and are found in cereal grains. This study was conducted to investigate the effect of carbohydrase enzymes or prebiotic oligosaccharides on growth performance, nutrient utilisation and weight of organs associated with the immune system in broilers fed wheat- or barley-based diets. RESULTS: In wheat-based diets, feed intake was lower (P < 0.05) following xylo-oligosaccharide supplementation, whereas in barley-based diets feed intake was greater (P < 0.05) following ß-glucanase supplementation. Gross energy digestibility was improved (P < 0.01) when either level of xylanase was added to wheat diets. Ileal digestible energy was greater (P < 0.01) in wheat diets including an additive compared with the control diet. In wheat diets, bursa weight was lower (P < 0.05) following xylo-oligosaccharide supplementation compared with the control treatment. CONCLUSIONS: The current study showed that supplemented carbohydrases or prebiotic oligosaccharides could alter the development of immune organs or small intestine without any significant effect on growth performance in broilers receiving nutrient-adequate diets. © 2018 The Authors. Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Effects of Respiratory Motion on Y-90 PET Dosimetry for SIRT.

Respiratory motion degrades the quantification accuracy of PET imaging by blurring the radioactivity distribution. In the case of post-SIRT PET-CT verification imaging, respiratory motion can lead to inaccuracies in dosimetric measures. Using an anthropomorphic phantom filled with 90Y at a range of clinically relevant activities, together with a respiratory motion platform performing realistic motions (10-15 mm amplitude), we assessed the impact of respiratory motion on PET-derived post-SIRT dosimetry. Two PET scanners at two sites were included in the assessment. The phantom experiments showed that device-driven quiescent period respiratory motion correction improved the accuracy of the quantification with statistically significant increases in both the mean contrast recovery (+5%, p = 0.003) and the threshold activities corresponding to the dose to 80% of the volume of interest (+6%, p < 0.001). Although quiescent period gating also reduces the number of counts and hence increases the noise in the PET image, its use is encouraged where accurate quantification of the above metrics is desired.

The internal dosimetry user group position statement on molecular radiotherapy.

The Internal Dosimetry User Group (IDUG) is an independent, non-profit group of medical professionals dedicated to the promotion of dosimetry in molecular radiotherapy (www.IDUG.org.uk). The Ionising Radiation (Medical Exposure) Regulations 2017, IR(ME)R, stipulate a requirement for optimisation and verification of molecular radiotherapy treatments, ensuring doses to non-target organs are as low as reasonably practicable. For many molecular radiotherapy treatments currently undertaken within the UK, this requirement is not being fully met. The growth of this field is such that we risk digressing further from IR(ME)R compliance potentially delivering suboptimal therapies that are not in the best interest of our patients. For this purpose, IDUG proposes ten points of action to aid in the successful implementation of this legislation. We urge stakeholders to support these proposals and ensure national provision is sufficient to meet the criteria necessary for compliance, and for the future advancement of molecular radiotherapy within the UK.

Comparison of 90Y SIRT predicted and delivered absorbed doses using a PSF conversion method.

PURPOSE: The aims of this study were to develop and apply a method to correct for the differences in partial volume effects of pre-therapy Technetium-99 m (99mTc)-MAA SPECT and post-therapy Yttrium-90 (90Y) bremsstrahlung SPECT imaging in selective internal radiation therapy, and to use this method to improve quantitative comparison of predicted and delivered 90Y absorbed doses. METHODS: The spatial resolution of 99mTc SPECT data was converted to that of 90Y SPECT data using a function calculated from 99mTc and 90Y point spread functions. This resolution conversion method (RCM) was first applied to 99mTc and 90Y SPECT phantom data to validate the method, and then to clinical data to assess the power of 99mTc SPECT imaging to predict the therapeutic absorbed dose. RESULTS: The maximum difference between absorbed doses to phantom spheres was 178%. This was reduced to 27% after the RCM was applied. The clinical data demonstrated differences within 38% for mean absorbed doses delivered to the normal liver, which were reduced to 20% after application of the RCM. Analysis of clinical data showed that therapeutic absorbed doses delivered to tumours greater than 100 cm3 were predicted to within 52%, although there were differences of up to 210% for smaller tumours, even after the RCM was applied. CONCLUSIONS: The RCM was successfully verified using phantom data. Analysis of the clinical data established that the 99mTc pre-therapy imaging was predictive of the 90Y absorbed dose to the normal liver to within 20%, but had poor predictability for tumours smaller than 100 cm3.

The similarity of the effect of carbohydrase or prebiotic supplementation in broilers aged 21 days, fed mixed cereal diets and challenged with coccidiosis infection.

The aim of this study was to investigate the effect on growth performance and nutrient utilisation when supplementing diets deficient in energy and protein with carbohydrase enzymes or xylo-oligosaccharide in broilers challenged with coccidia. 960 Ross 308 broilers were used in this 21-day study. The treatments were arranged into a 2×4 factorial with 2 challenge states (challenged and non-challenged) and 4 different additive types (control, xylanase alone, xylanase and ß-glucanase mixture and xylo-oligosaccharide). On day 14, the challenged group received 12× the recommended dose of coccidiosis vaccine while the non-challenged group received a sham treatment of water only. The birds and feed were weighed on days 0, 14 and 21. On day 21, two birds per pen were euthanized, the caeca were removed and the contents collected for short chain fatty acid analysis. Six more birds per pen were euthanized and ileal digesta were collected and pooled per pen for nutrient digestibility analysis. Feed intake was greater (P < 0.05) on days 14 and 21 when xylo-oligosaccharide was included in the diet compared to the xylanase and ß-glucanase mixture in birds challenged with coccidiosis. Including xylo-oligosaccharide in the diet improved (P < 0.05) the digestibility of nitrogen and supplementing diets with the xylanase and ß-glucanase mixture improved (P < 0.05) the digestibility of several amino acids. The concentration of arabinose and xylose was (P < 0.001) greater when broiler diets were supplemented with carbohydrase enzymes or xylo-oligosaccharide compared to the control. Although there was an increase in short chain fatty acid production due to the addition of carbohydrase enzymes or xylo-oligosaccharide, there was no additive effect on the %G+C profile of caecal bacteria however there was a negative effect of coccidiosis. In conclusion, the similarity in the response to carbohydrase enzymes or xylo-oligosaccharide supplementation illustrates that the hydrolysis products from carbohydrase activity may have prebiotic like effects.

IPEM topical report: current molecular radiotherapy service provision and guidance on the implications of setting up a dosimetry service.

Despite a growth in molecular radiotherapy treatment (MRT) and an increase in interest, centres still rarely perform MRT dosimetry. The aims of this report were to assess the main reasons why centres are not performing MRT dosimetry and provide advice on the resources required to set-up such a service. A survey based in the United Kingdom was developed to establish how many centres provide an MRT dosimetry service and the main reasons why it is not commonly performed. Twenty-eight per cent of the centres who responded to the survey performed some form of dosimetry, with 88% of those centres performing internal dosimetry. The survey showed that a 'lack of clinical evidence', a 'lack of guidelines' and 'not current UK practice' were the largest obstacles to setting up an MRT dosimetry service. More practical considerations, such as 'lack of software' and 'lack of staff training/expertise', were considered to be of lower significance by the respondents. Following on from the survey, this report gives an overview of the current guidelines, and the evidence available demonstrating the benefits of performing MRT dosimetry. The resources required to perform such techniques are detailed with reference to guidelines, training resources and currently available software. It is hoped that the information presented in this report will allow MRT dosimetry to be performed more frequently and in more centres, both in routine clinical practice and in multicentre trials. Such trials are required to harmonise dosimetry techniques between centres, build on the current evidence base, and provide the data necessary to establish the dose-response relationship for MRT.

Characterisation of the transcriptome of male and female wild-type guppy brains with RNA-Seq and consequences of exposure to the pharmaceutical pollutant, 17α-ethinyl estradiol.

Waterways are increasingly being contaminated by chemical compounds that can disrupt the endocrinology of organisms. One such compound is 17α-ethinyl estradiol (EE2), a synthetic estrogen used in the contraceptive pill. Despite considerable research interest in the effects of EE2 on reproduction and gene expression, surprisingly, only a few studies have capitalised on technologies, such as next-generation sequencing (NGS), to uncover the molecular pathways related to EE2 exposure. Accordingly, using high-throughput sequencing technologies, the aim of our study was to explore the effects of EE2 on brain transcriptome in wild-type male and female guppy (Poecilia reticulata). We conducted two sets of experiments, where fish were exposed to EE2 (measured concentrations: 8ng/L and 38ng/L) in a flow-through system for 21days. The effects on the brain transcriptome on both males and females were assessed using Illumina sequencing (MiSeq and HiSeq) platform followed by bioinformatics analysis (edgeR, DESeq2). Here, we report that exposure to EE2 caused both up- and downregulation of specific transcript abundances, and affected transcript abundance in a sex-specific manner. Specifically, we found 773 transcripts, of which 60 were male-specific, 61 female-specific and 285 treatment-specific. EE2 affected expression of 165 transcripts in males, with 88 downregulated and 77 upregulated, while in females, 120 transcripts were affected with 62 downregulated and 58 upregulated. Finally, RT-qPCR validation demonstrated that expression of transcripts related to transposable elements, neuroserpin and heat shock protein were significantly affected by EE2-exposure. Our study is the first to report brain transcriptome libraries for guppies exposed to EE2. Not only does our study provide a valuable resource, it offers insights into the mechanisms underlying the feminizing effects on the brains of organisms exposed to environmentally realistic concentrations of EE2.

Abdo-Man: a 3D-printed anthropomorphic phantom for validating quantitative SIRT.

BACKGROUND: The use of selective internal radiation therapy (SIRT) is rapidly increasing, and the need for quantification and dosimetry is becoming more widespread to facilitate treatment planning and verification. The aim of this project was to develop an anthropomorphic phantom that can be used as a validation tool for post-SIRT imaging and its application to dosimetry. METHOD: The phantom design was based on anatomical data obtained from a T1-weighted volume-interpolated breath-hold examination (VIBE) on a Siemens Aera 1.5 T MRI scanner. The liver, lungs and abdominal trunk were segmented using the Hermes image processing workstation. Organ volumes were then uploaded to the Delft Visualization and Image processing Development Environment for smoothing and surface rendering. Triangular meshes defining the iso-surfaces were saved as stereo lithography (STL) files and imported into the Autodesk® Meshmixer software. Organ volumes were subtracted from the abdomen and a removable base designed to allow access to the liver cavity. Connection points for placing lesion inserts and filling holes were also included. The phantom was manufactured using a Stratasys Connex3 PolyJet 3D printer. The printer uses stereolithography technology combined with ink jet printing. Print material is a solid acrylic plastic, with similar properties to polymethylmethacrylate (PMMA). RESULTS: Measured Hounsfield units and calculated attenuation coefficients of the material were shown to also be similar to PMMA. Total print time for the phantom was approximately 5 days. Initial scans of the phantom have been performed with Y-90 bremsstrahlung SPECT/CT, Y-90 PET/CT and Tc-99m SPECT/CT. The CT component of these images compared well with the original anatomical reference, and measurements of volume agreed to within 9 %. Quantitative analysis of the phantom was performed using all three imaging techniques. Lesion and normal liver absorbed doses were calculated from the quantitative images in three dimensions using the local deposition method. CONCLUSIONS: 3D printing is a flexible and cost-efficient technology for manufacture of anthropomorphic phantom. Application of such phantoms will enable quantitative imaging and dosimetry methodologies to be evaluated, which with optimisation could help improve outcome for patients.