PET imaging of steroid hormone receptor expression

Steroid hormone receptor (SHR) expression and changes in SHR expression compared to basal levels, whether upregulated, down-regulated, or mutated, form a distinguishing feature of some breast, ovarian, and prostate cancers. These receptors act to induce tumor proliferation. In the imaging context, total expression together with modulation of expression can yield predictive and prognostic information. Currently, biopsy for histologic assessment of SHR expression is routine for breast and prostate cancer; however, the technique is not well suited to the heterogeneous tumor environment and can lead to incorrect receptor expression assignment, which precludes effective treatment. The development of positron emission tomography (PET) radioligands to image receptor expression may overcome the difficulties associated with tumor heterogeneity and facilitate the assessment of metastatic disease

What ‘incomparable Jewells Havens, and sure harbours are’: the remains of late 16th century Dover harbour and their wider significance

SUMMARY: During excavations undertaken for the Dover Western Dock Revival Scheme, Kent, UK, Archaeology South-East (ASE; UCL Institute of Archaeology) encountered substantial remains associated with the development of the port of Dover. Despite natural limitations, especially in the form of silting from the River Dour and longshore drift, Dover has historically been a strategic location in which to maintain a port. The remains presented here comprise a nationally significant waterfront revealed during the revival scheme; that is, the Tudor engineering commonly attributed to Sir Thomas Digges, overseen by the Privy Council and commissioned by Elizabeth I

Development of a fluorine-18 radiolabelled fluorescent chalcone: evaluated for detecting glycogen"

Background: Glycogen is a multibranched polysaccharide of glucose produced by cells to store energy and plays a key role in cancer. A previously reported fluorescent probe (CDg4) was shown to selectively bind glycogen in mouse embryonic stem cells, however the molecule was not evaluated in cancer cells. We report the synthesis and biological evaluation of a dual-modality imaging probe based on CDg4, for positron emission tomography (PET) and fluorescence microscopy. Results: A fluorine-18 radiolabelled derivative of CDg4, ([18F]5) for in vivo quantification of total glycogen levels in cancer cells was developed and synthesised in 170 min with a non-decay corrected radiochemical yield (RCY n.d.c) of 5.1 ± 0.9 % (n = 4) in >98% radiochemical purity. Compound 5 and [18F]5 were evaluated in vitro for their potential to bind glycogen, but only 5 showed accumulation by fluorescence microscopy. The accumulation of 5 was determined to be specific as fluorescent signal diminished upon the digestion of carbohydrate polymers with α-amylase. PET imaging in non-tumour bearing mice highlighted rapid hepato-biliary-intestinal elimination of [18F]5 and almost complete metabolic degradation after 60 min in the liver, plasma and urine, confirmed by radioactive metabolite analysis. Conclusions: Fluorescent compound 5 selectively accumulated in glycogen containing cancer cells, identified by fluorescence microscopy; however, rapid in vivo metabolic degradation precludes further investigation of [18F]5 as a PET radiopharmaceutical

Synthesis and pre-clinical evaluation of a [18F] fluoromethyl-tanaproget derivative for imaging of progesterone receptor expression

The estrogen receptor (ER) and progesterone receptor (PR) are over-expressed in ∼50% of breast cancer lesions, and used as biomarkers to stratify patients for endocrine therapy. Currently, immunohistochemical (IHC) assessment of these lesions from a core-needle biopsy in deep-sited metastases has limitations associated with sampling error and lack of standardization. An alternative solution is positron emission tomography (PET)-based probes, which are inherently quantitative and capable of imaging the entire tumor, including metastases. This work features the synthesis and biological evaluation of a novel fluorinated derivative of tanaproget, a high affinity non-steroidal PR ligand, as a candidate for imaging PR expression in vivo. Radiolabeling of the candidate was achieved in a 15% ± 4 radiochemical yield (non-decay corrected) in one step from [18F]fluoromethyltosylate in 30 min. Cell uptake studies showed a significant difference between the radioligand uptake in PR+ and PR- cell lines; however, in vivo imaging was confounded by defluorination hypothesized to occur via iminium salt formation. Investigation into high affinity, metabolically stable non-steroidal PR ligands is currently ongoing

A general [F-18]AlF radiochemistry procedure on two automated synthesis platforms

The first general [18F]AIF automated radiolabelling procedure developed on the GE Tracerlab FX FN (Left) and Trasis AllInOne (Right) platforms.</p

Advanced laser micro-structuring of super-large-area optical films

ABSTRACT A novel laser micro-machining technique to produce high density micro-structures called Synchronized Image Scanning (SIS) was introduced a couple of years ago. Over this period of time, the technique was refined in a major effort to meet the needs of various industries. There is an increasing demand for micro-structuring of large and super large area optical films, e.g. for Rear Projection TV, anti counterfeit packaging material and 3D displays. Especially in the display industry, where the screens are ever increasing in size, established micro-structuring methods like e-beam milling, diamond turning or the reflow technique struggle to keep up with the development. This paper explains how it is possible to direct laser etch hundreds of millions of lenses into a 2 m x 1.5 m substrate. It looks at the advances made in SIS in recent years regarding seam reduction, overall accuracy and precision when structuring super large area optical films, and it presents the tools and subsystems needed to generate the features in those films. Furthermore, the potential of this exciting laser micro-machining technique for rapid prototyping for all sorts of optical and non-optical structures is mapped out

Measuring Metacognition in Cancer: Validation of the Metacognitions Questionnaire 30 (MCQ-30)

Objective The Metacognitions Questionnaire 30 assesses metacognitive beliefs and processes which are central to the metacognitive model of emotional disorder. As recent studies have begun to explore the utility of this model for understanding emotional distress after cancer diagnosis, it is important also to assess the validity of the Metacognitions Questionnaire 30 for use in cancer populations. Methods 229 patients with primary breast or prostate cancer completed the Metacognitions Questionnaire 30 and the Hospital Anxiety and Depression Scale pre-treatment and again 12 months later. The structure and validity of the Metacognitions Questionnaire 30 were assessed using factor analyses and structural equation modelling. Results Confirmatory and exploratory factor analyses provided evidence supporting the validity of the previously published 5-factor structure of the Metacognitions Questionnaire 30. Specifically, both pre-treatment and 12 months later, this solution provided the best fit to the data and all items loaded on their expected factors. Structural equation modelling indicated that two dimensions of metacognition (positive and negative beliefs about worry) were significantly associated with anxiety and depression as predicted, providing further evidence of validity. Conclusions These findings provide initial evidence that the Metacognitions Questionnaire 30 is a valid measure for use in cancer populations

A practical guide to automating fluorine-18 PET radiochemistry using commercially available cassette-based platforms

The automation of positron emission tomography (PET) radiochemistry using cassette-based automated radiosynthesis platforms is an essential component of clinical translation for the vast majority of 18F-based radiopharmaceuticals. The technology is widely adopted by good manufacturing practice (GMP) compliant radiopharmaceutical production facilities and research institutions developing novel tracers for clinical studies. Despite automation being fundamental to clinical translation, educational resources which introduce this branch of radiochemistry to the uninitiated are limited. Publications featuring automation assume previous experience of using these platforms and therefore, the detail they provide may not be sufficient for a novice user. In this Tutorial Account, we aim to bridge this knowledge gap and provide a resource for efficient automation for radiochemists across all levels of experience