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An EU legal analysis of the European Central Bank's Pandemic Emergency Purchase Programme (PEPP), originally published in March 2020 in EULawLive, updated to include more references to the ECB's pandemic responses (prudential, monetary policy) and the EU's NextGenerationEU Recovery and Resilience Facility, and to the Bundesverfassungsgericht's decision on the Public Sector Purchasing Programme (PSPP) and the Court of Justice of the European Union's judgment on the subject (Weiss).

Whether α4β2 nicotinic acetylcholine receptor (α4β2-nAChR) expression is reduced in early Alzheimer’s disease is controversial. Using (-)-[18F]Flubatine PET, Sabri, Meyer et al. report α4β2-nAChR deficiency in mild Alzheimer’s dementia, especially within the basal forebrain-cortical and septohippocampal cholinergic projections. Reduced α4β2-nAChR availability correlates with impaired episodic memory and executive function/working memory., In early Alzheimer’s dementia, there is a need for PET biomarkers of disease progression with close associations to cognitive dysfunction that may aid to predict further cognitive decline and neurodegeneration. Amyloid biomarkers are not suitable for that purpose. The α4β2 nicotinic acetylcholine receptors (α4β2-nAChRs) are widely abundant in the human brain. As neuromodulators they play an important role in cognitive functions such as attention, learning and memory. Post-mortem studies reported lower expression of α4β2-nAChRs in more advanced Alzheimer’s dementia. However, there is ongoing controversy whether α4β2-nAChRs are reduced in early Alzheimer’s dementia. Therefore, using the recently developed α4β2-nAChR-specific radioligand (−)-18F-flubatine and PET, we aimed to quantify the α4β2-nAChR availability and its relationship to specific cognitive dysfunction in mild Alzheimer’s dementia. Fourteen non-smoking patients with mild Alzheimer’s dementia, drug-naïve for cholinesterase therapy, were compared with 15 non-smoking healthy controls matched for age, sex and education by applying (−)-18F-flubatine PET together with a neuropsychological test battery. The one-tissue compartment model and Logan plot method with arterial input function were used for kinetic analysis to obtain the total distribution volume (VT) as the primary, and the specific binding part of the distribution volume (VS) as the secondary quantitative outcome measure of α4β2-nAChR availability. VS was determined by using a pseudo-reference region. Correlations between VT within relevant brain regions and Z-scores of five cognitive functions (episodic memory, executive function/working memory, attention, language, visuospatial function) were calculated. VT (and VS) were applied for between-group comparisons. Volume of interest and statistical parametric mapping analyses were carried out. Analyses revealed that in patients with mild Alzheimer’s dementia compared to healthy controls, there was significantly lower VT, especially within the hippocampus, fronto-temporal cortices, and basal forebrain, which was similar to comparisons of VS. VT decline in Alzheimer’s dementia was associated with distinct domains of impaired cognitive functioning, especially episodic memory and executive function/working memory. Using (−)-18F-flubatine PET in patients with mild Alzheimer’s dementia, we show for the first time a cholinergic α4β2-nAChR deficiency mainly present within the basal forebrain-cortical and septohippocampal cholinergic projections and a relationship between lower α4β2-nAChR availability and impairment of distinct cognitive domains, notably episodic memory and executive function/working memory. This shows the potential of (−)-18F-flubatine as PET biomarker of cholinergic α4β2-nAChR dysfunction and specific cognitive decline. Thus, if validated by longitudinal PET studies, (−)-18F-flubatine might become a PET biomarker of progression of neurodegeneration in Alzheimer’s dementia.

Recent case law on the scope of professional secrecy for the supervisory authorities in the financial sector and on the measure of openness of their files highlights the lack of coordination among the silos of supervision and the absence of clear and uniform professional secrecy rules across the financial sector. The introduction of the Single Supervisory Mechanism (SSM) makes this situation more acute: notwithstanding a centralised system of banking supervision, different approaches may exist in respect of access to files, even when based on EU legislation. This contribution addresses the accountability of supervisory authorities and, notably the European Central Bank (ECB), from the perspective of access to supervisory files, as a prelude to possible follow-up proceedings for failing supervision. Recent judgments in the Altmann, Baumeister, Buccioni, and UBS Europe cases slowly move the case law on supervisory secrecy towards more openness, long after Hillegom/Hillenius (1984). The judgments lead us to wonder whether the absence of legislative coordination and questionable drafting is being remedied by the judiciary. The variety of legislative provisions and relevant recent case law form the backdrop of our proposal to adopt a Regulation on professional secrecy for supervisory authorities in the financial sector, which would institute a single standard that is directly applicable across Member States and supervisory authorities.

This article examines the administrative remedy provided by the Administrative Board of Review (ABoR) of the European Central Bank (ECB), as part of the broader issue of the right of defence of natural and legal persons vis-Ã -vis ECB supervisory decisions within the Single Supervisory Mechanism (SSM). After presenting an overview of the review panels established in the financial sector in the EU, the article describes the experience with the ABoR by analysing its composition, its mandate and scope of review, the main procedural aspects and the relationship with judicial proceedings before the European Court of Justice. Particular attention is given to the substantial issues dealt with by the ABoR in its Opinions and to some of the major challenges faced in the first 2Â years of practice. Among them is the assessment of the correct application of national laws implementing EU legislation by the ECB. The paper identifies two aspects giving particular cause for concern and requiring legislative reforms: (1) the assessment of the suitability of the members of management bodies (fit and proper assessment) and (2) the inclusion of bank holding companies within the scope of banking supervision.

Radiolabeled tracers targeting the prostate-specific membrane antigen (PSMA) have become important radiopharmaceuticals for the PET-imaging of prostate cancer. In this connection, we recently developed the fluorine-18-labelled PSMA-ligand [18F]PSMA-1007 as the next generation radiofluorinated Glu-ureido PSMA inhibitor after [18F]DCFPyL and [18F]DCFBC. Since radiosynthesis so far has been suffering from rather poor yields, novel procedures for the automated radiosyntheses of [18F]PSMA-1007 have been developed. We herein report on both the two-step and the novel one-step procedures, which have been performed on different commonly-used radiosynthesisers. Using the novel one-step procedure, the [18F]PSMA-1007 was produced in good radiochemical yields ranging from 25 to 80% and synthesis times of less than 55 min. Furthermore, upscaling to product activities up to 50 GBq per batch was successfully conducted. All batches passed quality control according to European Pharmacopoeia standards. Therefore, we were able to disclose a new, simple and, at the same time, high yielding production pathway for the next generation PSMA radioligand [18F]PSMA-1007. Actually, it turned out that the radiosynthesis is as easily realised as the well-known [18F]FDG synthesis and, thus, transferable to all currently-available radiosynthesisers. Using the new procedures, the clinical daily routine can be sustainably supported in-house even in larger hospitals by a single production batch.

This paper, a draft of which was presented at the Conference Judicial review in the Banking Union and in the EU financial architecture, jointly organized by the Banca d’Italia and the European Banking Institute in Rome on 21 November 2017, discusses the contours of administrative review of prudential decisions of the European Central Bank (ECB) and the main issues facing the Administrative Board of Review (ABoR) of the ECB, of which the author is an alternate member. The paper continues with a discussion of limited options to enhance transparency on review, both administrative and judicial, followed by a discussion of the main cases pending at the European Court of Justice in the area of banking union: the French banking industry against the ECB; Credit Mutuel Arkea against the ECB; and Credit Agricole against the ECB. The L-Bank Case (T-122/15) and the Order in the Trasta Case (T-698/16) are summarised. The paper concludes with a call for more transparency and a possible alignment of financial sector review mechanisms. A postscript added after the Conference discusses developments since: judgments of 13 December 2017 in the Arkea cases (Cases T-712/15 and Case T-52/16) and the appeals lodged against the Order in the Trasta case by the bank and its shareholders (Case C-669/17 P), by the ECB (Case C-663/17 P) and by the Commission (Case C-665/17 P), promising a landmark judgment on admissibility of bank shareholders acting against the withdrawal of a banking authorisation. Also, references to the list of banking union-related judicial cases at the website of the European Banking Institute were added.

Reflections on context, transparency, review and culture of the Single Supervisory Mechanism (SSM), the Euro Area system of prudential supervision of banks, three years after its start. The paper discusses the 'cascade' of banking regulation (from global standards through EU legislation and harmonising technical regulations of the Commission to national laws, central bank acts and guidance) and suggests five ways to strengthen the Single Rulebook in the financial sector. The paper further explores transparency in the SSM, inter alia, discussing the public availability of Memoranda of Understanding among supervisory authorities, the ECB's Banking Supervision Manual, and information on administrative and judicial review of ECB acts, suggesting minor steps forward on the latter. The paper concludes with considerations on the context of banking union, highlighting the incidence of the often forgotten cultural aspect of integration of Europe.

Background Both enantiomers of [18F]flubatine are new radioligands for neuroimaging of α4β2 nicotinic acetylcholine receptors with positron emission tomography (PET) exhibiting promising pharmacokinetics which makes them attractive for different clinical questions. In a previous preclinical study, the main advantage of (+)-[18F]flubatine compared to (−)-[18F]flubatine was its higher binding affinity suggesting that (+)-[18F]flubatine might be able to detect also slight reductions of α4β2 nAChRs and could be more sensitive than (−)-[18F]flubatine in early stages of Alzheimer’s disease. To support the clinical translation, we investigated a fully image-based internal dosimetry approach for (+)-[18F]flubatine, comparing mouse data collected on a preclinical PET/MRI system to piglet and first-in-human data acquired on a clinical PET/CT system. Time-activity curves (TACs) were obtained from the three species, the animal data extrapolated to human scale, exponentially fitted and the organ doses (OD), and effective dose (ED) calculated with OLINDA. Results The excreting organs (urinary bladder, kidneys, and liver) receive the highest organ doses in all species. Hence, a renal/hepatobiliary excretion pathway can be assumed. In addition, the ED conversion factors of 12.1 μSv/MBq (mice), 14.3 μSv/MBq (piglets), and 23.0 μSv/MBq (humans) were calculated which are well within the order of magnitude as known from other 18F-labeled radiotracers. Conclusions Although both enantiomers of [18F]flubatine exhibit different binding kinetics in the brain due to the respective affinities, the effective dose revealed no enantiomer-specific differences among the investigated species. The preclinical dosimetry and biodistribution of (+)-[18F]flubatine was shown and the feasibility of a dose assessment based on image data acquired on a small animal PET/MR and a clinical PET/CT was demonstrated. Additionally, the first-in-human study confirmed the tolerability of the radiation risk of (+)-[18F]flubatine imaging which is well within the range as caused by other 18F-labeled tracers. However, as shown in previous studies, the ED in humans is underestimated by up to 50 % using preclinical imaging for internal dosimetry. This fact needs to be considered when applying for first-in-human studies based on preclinical biokinetic data scaled to human anatomy. Electronic supplementary material The online version of this article (doi:10.1186/s40658-016-0160-5) contains supplementary material, which is available to authorized users.

(−)-18F-flubatine is a promising tracer for neuroimaging of nicotinic acetylcholine receptors (nAChRs), subtype α4β2, using PET. Radiation doses after intravenous administration of the tracer in mice and piglets were assessed to determine the organ doses (ODs) and the effective dose (ED) to humans. The results were compared with subsequent clinical investigations in human volunteers. Methods: Twenty-seven female CD1 mice (weight ± SD, 28.2 ± 2.1 g) received intravenous injection of 0.75 ± 0.33 MBq of (−)-18F-flubatine. Up to 240 min after injection, 3 animals per time point were sacrificed and the organs harvested, weighed, and counted in a γ counter to determine mass and activity, respectively. Furthermore, whole-body PET scans of 5 female piglets (age ± SD, 44 ± 3 d; weight ± SD, 13.7 ± 1.7 kg) and 3 humans (2 men and 1 woman; age ± SD, 59.6 ± 3.9 y; weight ± SD, 74.3 ± 3.1 kg) were obtained up to 236 min (piglets) and 355 min (humans) after injection of 186.6 ± 7.4 and 353.7 ± 10.2 MBq of (−)-18F-flubatine, respectively, using a PET/CT scanner. The CT was used for delineation of the organs. Exponential curves were fitted to the time–activity-data, and time and mass scales were adapted to the human anatomy. The ODs were calculated using OLINDA/EXM (version 1.0); EDs were calculated with the tissue-weighting factors of ICRP103. Results: After the injection of (−)-18F-flubatine, there were no adverse or clinically detectable pharmacologic effects in any of the subjects. The highest activities after injection were found in the kidneys, urinary bladder, and liver. The urinary bladder receives the highest OD in all investigated species, followed by the kidneys and the liver for animals and humans, respectively. On the basis of mouse, piglet, and human kinetic data, the projected human ED of (−)-18F-flubatine was estimated to be 12.5 μSv/MBq in mice, 14.7 ± 0.7 μSv/MBq in piglets, and 23.4 ± 0.4 μSv/MBq in humans. Conclusion: As has been demonstrated for other PET radiotracers, preclinical (i.e., animal-derived) dosimetry underestimates the ED to humans, in the current case of (−)-18F-flubatine by 34%–44%.