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Aim: Microglial activation is increasingly recognised as a factor in the progression of Alzheimer’s disease (AD) and may be modified by systemic inflammatory signals including serum tumour necrosis factor (TNF)-α. The aim was to investigate whether blockade of peripheral TNF-α with peripheral inhibitors such as etanercept reduces microglial activation in prodromal AD. Methods: A one-year, multi-centre, phase 2, double-blind randomised placebo-controlled trial (RPCT) was performed, to assess the effect of weekly 50 mg s.c. etanercept in amyloid positive mild cognitive impaired participants on the change in microglial activation as measured by [11C](R)-PK11195 positron emission tomography (PET). Secondary objectives were to ascertain the change in cortical amyloid load on PET and the change in the Montreal Cognitive Assessment (MoCA). Results: Forty-four subjects consented to the study. Twenty-eight subjects failed screening including six subjects who were amyloid negative on visual read of the AmyvidTM PET scans. Thirteen of sixteen subjects with mild cognitive impairment (MCI) due to AD completed the baseline [11C](R)-PK11195 PET scan and were randomised to either placebo or etanercept. Three patients who consented were not able to complete screening due to early termination of the study following delays in study commencement. [11C](R)-PK11195 binding potential (BP) at baseline showed an almost global increase in MCI patients as compared to age-matched controls. Compliance to medication was high over the twelve-month trial period with etanercept being well tolerated. The study did not achieve statistical power to show a significant effect of etanercept over 52 weeks in the limited number of patients with MCI on microglial activation as measured by [11C](R)-PK11195 PET. Overall uptake of florbetapir in the follow up (FU) scans remained stable. The study was not powered to show statistical differences in psychometric ratings between groups. Conclusions: This study did not show evidence that treatment with etanercept over one year would modulate microglial activation in amyloid positive MCI patients (EudraCT identifier: 2015-002145-63, https://www.clinicaltrialsregister.eu; International Standard Randomised Controlled Trial Number identifier: ISRCTN12472821, https://www.isrctn.com).

The degradation of desiccants is important in designing natural gas conditioning processes.

Both affordability and stability are important for commercial-scale production and industrial applications of TiO2. In addition, the ability to tailor nanostructure and physicochemical properties can provide advantages for future applications. Herein a facile sol‒gel process was investigated by using titanyl sulfate as an inexpensive feedstock reacting with water in the media of acetic acid and isopropanol. An anatase phase was readily produced at 65 °C, followed by drying at 80 °C. The anatase was stable up to 800 °C due to the residual sulfate and nitrogen, where sulfate and ammonium slowly decomposed when heating beyond 400 °C. The monolithic TiO2 xerogels were composed of agglomerated TiO2 spherical particles with diameters of ca. 50 or 100 nm. The TiO2 spherical particles were built by anatase crystallites with a diameter of ca. 5 nm. As a result, the TiO2 exhibited both bimodal mesopores and macropores: Large mesopores (10‒30 nm) were present due to the void spaces between the TiO2 spherical particles, while the smaller mesopores (ca. 3 nm) were due to the void spaces between the anatase crystallites within each TiO2 particle. There were also larger macropores (a few micrometers), which were caused by gas bubbles generated during the sol‒gel reactions. From a mass transfer viewpoint, these large pores within TiO2 xerogels could have advantages in their potential applications for catalysis and/or filtration processes. Graphical Abstract

200 mg/kg gemcitabine affect growth of A549 xenografts.

Supplementary Table S1. Mean values [plus minus] standard deviations of different PET quantification approaches and number of samples analyzed. Supplementary Table S2. Mean values [plus minus] standard deviations of the figures presented in the results section and number of samples analyzed. Supplementary Table S3. Mean values [plus minus] standard deviation of peripheral blood counts measured at various time points after gemcitabine administration.

Gli36dEGFR cells were implanted. Thereafter, two imaging sequences were conducted: In sequence 1, T2w MRI and PET with [18F]DPA-714 was performed, while [18F]BR-351 PET and [18F]FET PET were conducted at day 13 and 14, respectively. In imaging sequence 2, T2w MRI and [18F]FET PET were conducted at day 12, followed by [18F]BR-351 and [18F]DPA-714 at day 13 and 14, respectively. After the last imaging experiment, mice were sacrificed and the brains immediately harvested for further analysis.

PET and CT images were co-registered using three CT-detectable, molecular sieve spheres (# 1-3) rinsed in radiotracer solution. After segmentation of spheres in the CT image (arrows), PET and CT images were superimposed by using the automated "Landmark tool" provided by the Vinci software. The "Magic tool" was applied for minor corrections of co-registrations. The resulting resliced PET image was saved for further processing. In a second step, MR and CT images were superimposed using the "Fusion- and Magic tool". For illustration MR is pseudocolored in red, while the CT was inverted in color (black). The CT contour was further superimposed to demonstrate co-registration accuracy. Selected bone structures were used as additional quality measures of image registration. The resliced CT image was saved with the new transformation matrix. In a last step, the before mentioned transformation of the CT (CTMR) was transferred to the PET, resulting in co-registration of PET/MR/CT. This workflow was repeated for every PET scan per mouse.

Immunohistochemical analysis of bone marrow tissue from the femur showed that proliferation was severely impaired within hours of gemcitabine therapy, whereas recovery could be noted thereafter.

Legends for supplementary figures.

Mean and standard deviation, as well as number of samples analyzed (in brackets), of other PET image quantification approaches.

(A) T/B ratios, (B-D) tracer volumes, (E-J) areas of unique tracer uptake and overlapping regions. No significant effect on volumetric data was observed based on the order of imaging experiments.

[18F]FLT accumulation in hematopoietic organs could also be noted after paclitaxel therapy.

Gemcitabine induces increased apoptosis in H1975 tumors on d5.

Ki67 immunohistochemical staining.

Supplementary Figure Legends 1-5

Preliminary analysis of other thymidine metabolism proteins did not indicate their involvement in changes in [18F]FLT in hematopoietic compartments after gemcitabine therapy.

Molecular imaging with the PET tracer 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) allows assessment of the proliferative state of organs in vivo. Although used primarily in the oncology clinic, it can also shed light on the proliferation of other tissues, as demonstrated here for monitoring hematopoietic organs that recover after myelosuppressive chemotherapy. In the NMRI nude mouse model, we observed up to a 4.5-fold increase in [18F]FLT uptake in bone marrow and spleen on days 2, 3, and 5 after treatment with gemcitabine, a chemotherapeutic agent that is powerfully myelosuppressive in the model. Specifically, we observed (i) a reduced spleen weight; (ii) reduced bone marrow cell counts and proliferation (BrdUrd flow cytometry, spleen IHC; 6 hours/day 1); and (iii) reduced leukocytes in peripheral blood (day 5). In conclusion, our results show how [18F]FLT PET can provide a powerful tool to noninvasively visualize the proliferative status of hematopoietic organs after myelosuppressive therapy. Cancer Res; 76(24); 7089–95. ©2016 AACR.

Outline of the experimental schedule pursued.

TS and hENT1 expression are not altered 6 h after gemcitabine.

(A) An elliptical VOI (yellow) was drawn in the striatum. (B) Another elliptical VOI (green) was placed over the affected hemisphere. (C) After application of a thresholding based on the control VOI. The same original VOIs (left and middle) were used for all animals for individual thresholding.

Mean and standard deviation, as well as number of samples analyzed (in brackets), of the data presented in this article.

The tumor microenvironment is highly heterogeneous. For gliomas, the tumor-associated inflammatory response is pivotal to support growth and invasion. Factors of glioma growth, inflammation, and invasion, such as the translocator protein (TSPO) and matrix metalloproteinases (MMP), may serve as specific imaging biomarkers of the glioma microenvironment. In this study, noninvasive imaging by PET with [18F]DPA-714 (TSPO) and [18F]BR-351 (MMP) was used for the assessment of localization and quantification of the expression of TSPO and MMP. Imaging was performed in addition to established clinical imaging biomarker of active tumor volume ([18F]FET) in conjunction with MRI. We hypothesized that each imaging biomarker revealed distinct areas of the heterogeneous glioma tissue in a mouse model of human glioma. Tracers were found to be increased 1.4- to 1.7-fold, with [18F]FET showing the biggest volume as depicted by a thresholding-based, volumes of interest analysis. Tumor areas, which could not be detected by a single tracer and/or MRI parameter alone, were measured. Specific compartments of [18F]DPA-714 (14%) and [18F]BR-351 (11%) volumes along the tumor rim could be identified. [18F]DPA-714 (TSPO) and [18F]BR-351 (MMP) matched with histology. Glioma-associated microglia/macrophages (GAM) were identified as TSPO and MMP sources. Multitracer and multimodal molecular imaging approaches may allow us to gain important insights into glioma-associated inflammation (GAM, MMP). Moreover, this noninvasive technique enables characterization of the glioma microenvironment with respect to the disease-driving cellular compartments at the various disease stages. Cancer Res; 77(8); 1831–41. ©2017 AACR.

Legends for Supplementary Figures S1-S5

3′-Deoxy-3′-[18F]fluorothymidine positron emission tomography ([18F]FLT-PET) and diffusion-weighted MRI (DW-MRI) are promising approaches to monitor tumor therapy response. Here, we employed these two imaging modalities to evaluate the response of lung carcinoma xenografts in mice after gemcitabine therapy. Caliper measurements revealed that H1975 xenografts responded to gemcitabine treatment, whereas A549 growth was not affected. In both tumor models, uptake of [18F]FLT was significantly reduced 6 hours after drug administration. On the basis of the gemcitabine concentration and [18F]FLT excretion measured, this was presumably related to a direct competition of gemcitabine with the radiotracer for cellular uptake. On day 1 after therapy, [18F]FLT uptake was increased in both models, which was correlated with thymidine kinase 1 (TK1) expression. Two and 3 days after drug administration, [18F]FLT uptake as well as TK1 and Ki67 expression were unchanged. A reduction in [18F]FLT in the responsive H1975 xenografts could only be noted on day 5 of therapy. Changes in ADCmean in A549 xenografts 1 or 2 days after gemcitabine did not seem to be of therapy-related biological relevance as they were not related to cell death (assessed by caspase-3 IHC and cellular density) or tumor therapy response. Taken together, in these models, early changes of [18F]FLT uptake in tumors reflected mechanisms, such as competing gemcitabine uptake or gemcitabine-induced thymidylate synthase inhibition, and only reflected growth-inhibitory effects at a later time point. Hence, the time point for [18F]FLT-PET imaging of tumor response to gemcitabine is of crucial importance. Cancer Res; 76(24); 7096–105. ©2016 AACR.

An exemplary subset of n=6 mice were randomly assessed for intra-rater reproducibility. (A-E) [18F]DPA-714 and [18F]FET images were on two consecutive days repeatedly co-registered. Volumetry was performed twice (coreg 2 and coreg 3) and compared to the data reported in the main text (coreg 1). Dotted lines represent the overall mean for all n=20 animals reported in the main text. No significant changes for all parameters, except for the "percentage of [18F]DPA-714 only" between coreg 1 and 3, was found over the three different time points of co-registration.

Outline of the experimental schedule pursued.

Mean and standard deviation, as well as number of samples analyzed (in brackets), of [18F]FLT uptake in organs other than the tumor 6 h after gemcitabine (%IDmax/mL)

Zusammenfassung Anamnese und klinischer Befund Der folgende Case Report berichtet über die Aufnahme eines Patienten mit einem akut auf chronischen Nierenversagen unter BCG-(Bacillus-Calmette-Guérin)-Erhaltungstherapie bei bekanntem Blasenkarzinom mit sonografisch dargestelltem Harnstau II.–III. Grades ohne Restharn. Die zystoskopisch nachweisbare beidseitige intramurale Engstelle kann im Rahmen der BCG-Therapie gedeutet werden. Therapie und Verlauf Es folgte die Anlage einer Doppel-J-Schiene, worunter sich die Nierenretentions-Parameter schnell besserten. Folgerung Ein postrenales Nierenversagen ist mit 5 % eher selten, wobei in der differenzialdiagnostischen Überlegung neben anderen Ursachen auch eine medikamentös-induzierte Ursache (z. B. BCG) einzubeziehen ist.

Contains fulltext : 283280.pdf (Publisher’s version ) (Open Access)

Purpose Multimodal molecular imaging allows a direct coregistration of different images, facilitating analysis of the spatial relation of various imaging parameters. Here, we further explored the relation of proliferation, as measured by [18F]FLT PET, and water diffusion, as an indicator of cellular density and cell death, as measured by diffusion-weighted (DW) MRI, in preclinical tumor models. We expected these parameters to be negatively related, as highly proliferative tissue should have a higher density of cells, hampering free water diffusion. Procedures Nude mice subcutaneously inoculated with either lung cancer cells (n = 11 A549 tumors, n = 20 H1975 tumors) or colorectal cancer cells (n = 13 Colo205 tumors) were imaged with [18F]FLT PET and DW-MRI using a multimodal bed, which was transferred from one instrument to the other within the same imaging session. Fiducial markers allowed coregistration of the images. An automatic post-processing was developed in MATLAB handling the spatial registration of DW-MRI (measured as apparent diffusion coefficient, ADC) and [18F]FLT image data and subsequent voxel-wise analysis of regions of interest (ROIs) in the tumor. Results Analyses were conducted on a total of 76 datasets, comprising a median of 2890 data points (ranging from 81 to 13,597). Scatterplots showing [18F]FLT vs. ADC values displayed various grades of relations (Pearson correlation coefficient (PCC) varied from − 0.58 to 0.49, median: -0.07). When relating PCC to tumor volume (median: 46 mm3, range: 3 mm3 to 584 mm3), lung tumors tended to have a more pronounced negative spatial relation of [18F]FLT and ADC with increasing tumor size. However, due to the low number of large tumors (> ~ 200 mm3), this conclusion has to be treated with caution. Conclusions A spatial relation of water diffusion, as measured by DW-MRI, and cellular proliferation, as measured by [18F]FLT PET, cannot be detected in the experimental datasets investigated in this study.

Evaluation of adsorbent integrity over thousands of cycles is necessary to establish the service time and sustainability of adsorbents employed in industrial dehydration. Herein, an adsorption apparatus for rapidly cycling multiple adsorbents through a thermal swing adsorption process is introduced with results for 2000 cycles. This apparatus has eight sample cells arranged in parallel, which are embedded in an aluminum block for rapid heating and cooling. At the outlet of each cell, the water content and temperatures are measured using capacitance relative humidity sensors, which incorporate resistance thermometers. The analysis of the breakthrough curves generated for each adsorbent gives inference into the change in water uptake capacity over continuous cycling. To handle the large sets of data generated by this instrument, an automated analysis program was implemented. To demonstrate the functionality of the instrument, zeolites 4A and 13X were cycled in a thermal swing process over 2000 cycles and the change in the uptake capacity was monitored by the analysis of the breakthrough plots for each cycle. Furthermore, the results of the breakthrough analyses were verified with the thermogravimetric analysis of the adsorbents. From these experiments, zeolites 4A and 13X were observed to lose 7 ± 3 and 19 ± 7% of the adsorption capacity, respectively.

ZusammenfassungSchwerwiegend verlaufende COVID-19-Erkrankungen betreffen vorwiegend die ältere Bevölkerung. Die Mortalität der hospitalisierten COVID-19-Patienten im Alter über 80 Jahre liegt international bei bis zu 54 %. Daher ist ein Blick auf die Erkrankung aus geriatrischer Perspektive erforderlich. Diagnostik und Therapie der COVID-19-Erkrankung unterscheiden sich bei den älteren Patienten nicht grundsätzlich von der bei jüngeren Patienten. Allerdings ist bei Patienten im hohen Alter gehäuft mit einer atypischen Symptomatik zu rechnen. Der Rehabilitationsbedarf nach durchgemachter Infektion ist bei älteren COVID-19-Patienten deutlich höher als bei jüngeren Patienten. Paradoxerweise steht der Notwendigkeit vermehrter Rehabilitationsleistungen jedoch ein sinkendes Angebot geriatrischer Rehabilitationsmöglichkeiten gegenüber, da viele Abteilungen entweder geschlossen oder deren Behandlungskapazitäten reduziert wurden. Generell sollten Quarantäne- und Isolationsmaßnahmen in der älteren Bevölkerung verstärkt auf ihre Verhältnismäßigkeit überprüft werden, da die gesundheitlichen und emotionalen Auswirkungen gravierend sein können. Angesichts der ungünstigen Prognose bei hochaltrigen COVID-19-Patienten kommt der Berücksichtigung des Patientenwillens eine besondere Bedeutung zu. Daher sollten Angehörige und Ärzte sich frühzeitig, d. h. möglichst bereits vor dem Auftreten einer Infektion, bemühen, diesen zu eruieren und angemessen zu dokumentieren. Erfreulicherweise lassen die bisherigen Daten hoffen, dass die Impfung mit den in Deutschland zugelassenen mRNA-Impfstoffen gegen SARS-CoV‑2 auch im hohen Alter gut wirksam ist.

Rationale: The heterogeneous nature of gliomas makes the development and application of novel treatments challenging. In particular, infiltrating myeloid cells play a role in tumor progression and therapy resistance. Hence, a detailed understanding of the dynamic interplay of tumor cells and immune cells in vivo is necessary. To investigate the complex interaction between tumor progression and therapy-induced changes in the myeloid immune component of the tumor microenvironment, we used a combination of [18F]FET (amino acid metabolism) and [18F]DPA-714 (TSPO, GAMMs, tumor cells, astrocytes, endothelial cells) PET/MRI together with immune-phenotyping. The aim of the study was to monitor temozolomide (TMZ) treatment response and therapy-induced changes in the inflammatory tumor microenvironment (TME). Methods: Eighteen NMRInu/nu mice orthotopically implanted with Gli36dEGFR cells underwent MRI and PET/CT scans before and after treatment with TMZ or DMSO (vehicle). Tumor-to-background (striatum) uptake ratios were calculated and areas of unique tracer uptake (FET vs. DPA) were determined using an atlas-based volumetric approach. Results: TMZ therapy significantly modified the spatial distribution and uptake of both tracers. [18F]FET uptake was significantly reduced after therapy (-53 ± 84%) accompanied by a significant decrease of tumor volume (-17 ± 6%). In contrast, a significant increase (61 ± 33%) of [18F]DPA-714 uptake was detected by TSPO imaging in specific areas of the tumor. Immunohistochemistry (IHC) validated the reduction in tumor volumes and further revealed the presence of reactive TSPO-expressing glioma-associated microglia/macrophages (GAMMs) in the TME. Conclusion: We confirm the efficiency of [18F]FET-PET for monitoring TMZ-treatment response and demonstrate that in vivo TSPO-PET performed with [18F]DPA-714 can be used to identify specific reactive areas of myeloid cell infiltration in the TME.

Background The aim of our prospective multicentre study is to evaluate the five-year follow-up outcomes of primary reverse shoulder replacement utilizing two different designs of glenoid baseplates. Methods There were 159 reverse shoulder replacements (91 cemented and 68 uncemented stems, 67 Trabecular Metal baseplates and 92 Anatomical Shoulder baseplates in 152 patients (99 women) with a mean age of 74.5 (58–90) years. The principal diagnosis was rotator cuff arthropathy in 108 shoulders. Results Clinical and functional results improved significantly overall; the adjusted Constant Murley score improved from 28.2 ± 13.3 pre-operatively to 75.5 ± 22.8 ( p Conclusions Reverse total shoulder arthroplasty restores the function in shoulder with significant improvements in function and moderate complications with minor differences between both designs of baseplates that were not reflected clinically.

The introduction of gas warfare in World War One was impactful, as it both expanded the breadth of warfare and fueled the invention of techniques required to treat these new injuries. Gas injuries were responsible for 91,000 of 1.3 million deaths in World War One. Gassed soldiers had wounds which the world had never seen. They presented in large scale to medical tents and base hospitals across Europe. As gas casualties poured in, doctors and nurses had to treat these conditions in the best way they knew. Gas warfare changed how war was performed and how casualties of this attack were treated. The techniques learned from treating the multitudes of men with gas burns led to advances in the field of burn care, which have helped to improve mortality and reduce morbidity in hospitals across the world.

Glioblastoma is the most common primary brain tumor, highly aggressive by being proliferative, neovascularized and invasive, heavily infiltrated by immunosuppressive glioma-associated myeloid cells (GAMs), including glioma-associated microglia/macrophages (GAMM) and myeloid-derived suppressor cells (MDSCs). Quantifying GAMs by molecular imaging could support patient selection for GAMs-targeting immunotherapy, drug target engagement and further assessment of clinical response. Magnetic resonance imaging (MRI) and amino acid positron emission tomography (PET) are clinically established imaging methods informing on tumor size, localization and secondary phenomena but remain quite limited in defining tumor heterogeneity, a key feature of glioma resistance mechanisms. The combination of different imaging modalities improved the in vivo characterization of the tumor mass by defining functionally distinct tissues probably linked to tumor regression, progression and infiltration. In-depth image validation on tracer specificity, biological function and quantification is critical for clinical decision making. The current review provides a comprehensive overview of the relevant experimental and clinical data concerning the spatiotemporal relationship between tumor cells and GAMs using PET imaging, with a special interest in the combination of amino acid and translocator protein (TSPO) PET imaging to define heterogeneity and as therapy readouts.

Oxygen minimum zones (OMZs) play a critical role in global biogeochemical cycling and act as barriers to dispersal for marine organisms. OMZs are currently expanding and intensifying with climate change, however past distributions of OMZs are relatively unknown. Here we present evidence for widespread pelagic OMZs during the Pliocene (5.3-2.6 Ma), the most recent epoch with atmospheric CO2 analogous to modern (~400-450 ppm). The global distribution of OMZ-affiliated planktic foraminifer, Globorotaloides hexagonus, and Earth System and Species Distribution Models show that the Indian Ocean, Eastern Equatorial Pacific, eastern South Pacific, and eastern North Atlantic all supported OMZs in the Pliocene, as today. By contrast, low-oxygen waters were reduced in the North Pacific and expanded in the North Atlantic in the Pliocene. This spatially explicit perspective reveals that a warmer world can support both regionally expanded and contracted OMZs, with intermediate water circulation as a key driver.

To evaluate medication-related risks in older patients with cancer and their association with severe toxicity during antineoplastic therapy.This is a secondary analysis of two prospective, single-center observational studies which included patients ≥ 70 years with cancer. The patients' medication lists were investigated regarding possible risks: polymedication (defined as the use of ≥ 5 drugs), potentially inappropriate medication (PIM), and relevant potential drug-drug interactions (rPDDI). The risks were analyzed before and after start of cancer therapy. Severe toxicity during antineoplastic therapy was captured from medical records according to the Common Terminology Criteria for Adverse Events (CTCAE). The association between grade ≥ 3 toxicity and medication risks was evaluated by univariate as well as multivariate regression adjusted by ECOG and age.The study cohort comprised 136 patients (50% female, mean age 77 years, 42% hematological malignancies). Before the start of cancer therapy, patients took on average 5 drugs as long-term medication and 52% of patients were exposed to polymedication. More than half of patients used at least one PIM. Approximately one third of patients exhibited rPDDI. The prevalence of medication risks increased after start of cancer therapy. rPDDI were significantly associated with severe overall toxicity (OR, 5.07; p = 0.036; 95% Confidence Interval (CI) 1.11-23.14; toxicity in patients with rPDDI 94.1% (32/34) vs 75.9% (60/79) in patients without rPDDI) and hematological toxicity (OR, 3.95; p = 0.010; 95% CI 1.38-11.29; hematological toxicity in patients with rPDDI 85.3% (29/34) vs 59.5% (47/79) in patients without rPDDI). In the multivariate analysis adjusted by ECOG and age, only the association for rPDDI with hematological toxicity remained statistically significant (OR, 4.51; p = 0.007; 95% CI 1.52-13.38). These findings should be further investigated in larger studies.Medication risks are common in older patients with cancer and might be associated with toxicity. This raises the need for tailored interventions to ensure medication safety in this patient cohort.

Geriatric medicine is a rapidly evolving field that addresses diagnostic, therapeutic and care aspects of older adults. Some disabilities and disorders affecting cognition (e.g. dementia), motor function (e.g. stroke, Parkinson’s disease, neuropathies), mood (e.g. depression), behavior (e.g. delirium) and chronic pain disorders are particularly frequent in old subjects. As knowledge about these age-associated conditions and disabilities is steadily increasing, the integral implementation of neurogeriatric knowledge in geriatric medicine and specific neurogeriatric research is essential to develop the field. This article discusses how neurological know-how could be integrated in academic geriatric medicine to improve care of neurogeriatric patients, to foster neurogeriatric research and training concepts and to provide innovative care concepts for geriatric patients with predominant neurological conditions and disabilities.

Purpose Primary angiitis of the central nervous system (PACNS) is a heterogeneous, rare, and poorly understood inflammatory disease. We aimed at non-invasive imaging of activated microglia/macrophages in patients with PACNS by PET-MRI targeting the translocator protein (TSPO) with [18F]DPA-714 to potentially assist differential diagnosis, therapy monitoring, and biopsy planning. Methods In total, nine patients with ischemic stroke and diagnosed or suspected PACNS underwent [18F]DPA-714-PET-MRI. Dynamic PET scanning was performed for 60 min after injection of 233 ± 19 MBq [18F]DPA-714, and MRI was simultaneously acquired. Results In two PACNS patients, [18F]DPA-714 uptake patterns exceeded MRI correlates of infarction, whereas uptake was confined to the infarct in four patients where initial suspicion of PACNS could not be confirmed. About three patients with PACNS or cerebral predominant lymphocytic vasculitis showed no or only faintly increased uptake. Short-term [18F]DPA-714-PET follow-up in a patient with PACNS showed reduced lesional [18F]DPA-714 uptake after anti-inflammatory treatment. Biopsy in the same patient pinpointed the source of tracer uptake to TSPO-expressing immune cells. Conclusions [18F]DPA-714-PET imaging may facilitate the diagnosis and treatment monitoring of PACNS. Further studies are needed to fully understand the potential of TSPO-PET in deciphering the heterogeneity of the disease.

Vor Diagnosestellung einer malignen Erkrankung konnen neurologische Krankheitsbilder auftreten, die durch eine fehlgeleitete Immunreaktion gegen intrazellulare Antigene oder neuronale Oberflachenantigene ausgelost werden. Zu den haufigsten paraneoplastischen Erkrankungen gehort die subakute Kleinhirndegeneration. Die haufigsten beschriebenen paraneoplastischen Antikorper sind Anti Hu, CRMP5/CV2, Amphiphysin, Ma/Ta bei kleinzelligen Lungenkarzinomen, Mammakarzinomen und Lymphomen. Wir berichten uber einen 67jahrigen Patienten mit einer cerebellaren Symptomatik und ungewollter Gewichtsabnahme von 10 kg, bei dem im Verlauf der diagnostischen Aufarbeitung ein nichtkleinzelliges Bronchialkarzinom gefunden wurde. Serologisch gelang der Nachweis von erhohten Anti-Tr3-Antikorpern, welche typischerweise bei der subakuten Kleinhirndegeneration assoziiert mit einem Morbus Hodgkin, seltener bei Non-Hodgkin Lymphomen gefunden werden. Unter tumoradaptierter Therapie und intravenoser Immunglobulingabe verbesserten sich die neurologischen Kleinhirnsymptome. Im klinischen Verlauf wird sich zeigen, ob die Anti-Tr3 Antikorper tatsachlich im Rahmen des nicht kleinzelligen Bronchialkarzinoms aufgetreten sind oder der Patient noch ein Lymphom entwickeln wird.