[Nuclear medicine procedure guideline for sentinel lymph node localization]. / DGN-Handlungsempfehlung (S1-Leitlinie) ­ Version 3.

The authors present a procedure guideline for scintigraphic detection of sentinel lymph nodes in malignant melanoma, in breast cancer, in penile and vulva tumors, in head and neck cancer, and in prostate carcinoma. Important goals of sentinel lymph node scintigraphy comprise reduction of the extent of surgery, lower postoperative morbidity and optimization of histopathological examination focussing on relevant lymph nodes. Sentinel lymph node scintigraphy itself does not diagnose tumorous lymph node involvement and is not indicated when lymph node or distant metastases have been definitely diagnosed before sentinel lymph node scintigraphy. Procedures are compiled with the aim to reliably localise sentinel lymph nodes with a high detection rate typically in early tumour stages. New aspects in this guideline are new radiopharmaceuticals such as tilmanocept and Tc-99m-PSMA and SPECT/CT allowing an easier anatomical orientation. Initial dynamic lymphoscintigraphy in breast cancer is of little significance nowadays. Radiation exposure is low so that pregnancy is not a contraindication for sentinel lymph node scintigraphy. A one-day protocol should preferentially be used. Even with high volumes of scintigraphic sentinel lymph node procedures surgeons, theatre staff and pathologists receive a radiation exposure < 1 mSv/year so that they do not require occupational radiation surveillance. Aspects of quality control were included (scintigraphy, quality control of gamma probe, 6 h SLN course for surgeons, certified breast centers, medical surveillance center).

[What actually happens in hybrid imaging?] / Was passiert eigentlich in der Hybridbildgebung?

CLINICAL/METHODOLOGICAL ISSUE: The goal of this article is to shed light on innovations in perfusion imaging and the fields of application that have opened up in hybrid imaging of the heart. STANDARD RADIOLOGICAL METHODS: As before, the most commonly used modalities in hybrid imaging are single photon emission computed tomography (SPECT) and positron emission tomography/computed tomography (PET/CT). Perfusion tracers and the radioactively labeled glucose analog 18F­fluorodeoxyglucose (FDG) are commonly used for vitality imaging. METHODICAL INNOVATIONS: Use of PET/MRI (magnetic resonance imaging) is becoming increasingly widespread. In addition, FDG is also increasingly applied in imaging infectious and inflammatory myocardial diseases. Furthermore, novel tracers are used, such as the amyloid-specific tracers in cardiac amyloidosis. PERFORMANCE: Overall, this development has led to an increasing use of hybrid imaging techniques. These still include myocardial perfusion imaging, but are also used in inflammatory and infectious diseases such as endocarditis, myocarditis and sarcoidosis, as well as in underestimated diseases such as cardiac amyloidosis. The use of tracers has led to the creation of new fields of application in hybrid imaging. PRACTICAL RECOMMENDATIONS: Hybrid imaging combining myocardial perfusion and coronary visualization seems to be particularly advantageous in complex cases such as multivessel disease. In infectious and inflammatory myocardial diseases, FDG PET/CT or PET/MRI has clearly demonstrated its added value. New fields of application are very promising, but their significance has yet to be clearly demonstrated.

Maternal body mass index, smoking status and small for gestational age: an Australian retrospective cohort study.

OBJECTIVES: Both maternal body mass index (BMI) and smoking during pregnancy have been associated with a range of adverse maternal and infant birth outcomes. This study aimed to identify whether these independent variables had an interacting relationship with small for gestational age in an Australian obstetric cohort. STUDY DESIGN: A retrospective cohort design used data from the Birthing Outcomes System of a major tertiary hospital in Australia. METHODS: A total of 14,487 singleton births between January 2008 and December 2013 were included in the analysis. Chi-squared tests and one-way analysis of variance were used for the comparison of categorical and continuous variables, respectively. Adjusted odds ratios (AORs) were calculated to determine the association of smoking status with the outcome variable of interest, and these are reported for each maternal BMI category. RESULTS: Of the 14,487 women, 716 (4.9%) were underweight (BMI ≤18 kg/m2), 7268 (50.2%) had healthy weight (BMI = 19-24 kg/m2), 3658 (25.3%) were overweight (BMI = 25-29 kg/m2), 1558 (10.8%) had class I obesity (BMI = 30-34 kg/m2), 711 (4.9%) had class II obesity (BMI = 35-39 kg/m2) and 576 (3.9%) had class III obesity (BMI = 40+ kg/m2). Of all women, 10.8% reported being current smokers, 82.0% reported to have never smoked and 4.0% reported to have stopped smoking during or before pregnancy. Smokers with a BMI ≥40 kg/m2 were 4.5 (AOR = 4.508; 95% confidence interval: 2.068-9.828) times more likely to give birth to a small-for-gestational-age infant than non-smokers within the same BMI category. This increased risk was not observed in women who ceased smoking before or during pregnancy. CONCLUSIONS: Our study supports the efficacy of antismoking policies within maternal public health. In addition, greater support with respect to smoking cessation is indicated for women during pregnancy with an elevated BMI.

[PSMA-based theranostics for prostate cancer : From imaging to treatment]. / PSMA-basierte Theranostik beim Prostatakarzinom : Von der Bildgebung zur Therapie.

BACKGROUND: In recent years nuclear medicine theranostics using radiolabeled prostate-specific membrane antigen (PSMA) ligands have gained increasing importance in the management of prostate cancer. AIM: The aim of this work is to highlight the value of theranostic concepts using radiolabeled PSMA ligands for both the diagnostic work-up and treatment of advanced prostate cancer. MATERIAL AND METHODS: The currently available knowledge in the literature is summarized and presented. RESULTS: The use of PSMA in positron emission tomography-computed tomography (PET/CT) shows a high sensitivity and specificity for prostate cancer imaging, particularly in patients with biochemical recurrences. Furthermore, promising results are also reported for staging of primary prostate cancer and treatment monitoring. In addition, radioligand therapy using alpha and beta emitters is a promising third line treatment option in intensively pretreated patients with metastases. The reduction of side effects and optimization of the treatment sequence of radioligand therapy is of increasing importance. CONCLUSION: Nuclear medicine theranostics have an increasing clinical impact on the diagnostics and treatment of prostate cancer.

Effect of Suboccipital Release on Pain Perception and Autonomic Reflex Responses to Ischemic and Cold Pain.

OBJECTIVE/SUBJECTS: To determine the autonomic effects of suboccipital release (SOR) during experimentally induced pain, 16 healthy subjects (eight women, eight men) experienced ischemic (forearm postexercise muscle ischemia [PEMI]) and cold (cold pressor test [CPT]) pain. DESIGN: Beat-to-beat heart rate (electrocardiogram), mean arterial blood pressure (finger photoplethysmography), baroreflex sensitivity (transfer function analysis), and pain perception were measured. SOR or a sham (modified yaw; 30 cycles/min) was performed in minute 2 of pain. RESULTS: PEMI increased blood pressure by 23 ± 2 and 20 ± 2 mmHg; no differences occurred between SOR or yaw. PEMI modestly elevated heart rate during ischemia, followed by significant reduction from baseline with SOR (-3 ± 2 bpm) and yaw (-4 ± 2 bpm); no differences were observed between treatments. CPT increased blood pressure (SOR = 11 ± 1, yaw = 9 ± 2 mmHg) and heart rate (SOR = 10 ± 2, yaw = 8 ± 3 bpm) before SOR and yaw. Neither treatment nor sham blunted blood pressure increases (SOR = 25 ± 2, yaw = 22 ± 2 mmHg) during CPT; both decreased heart rate (SOR = -3 ± 2, yaw = -2 ± 2 bpm) from baseline. PEMI and CPT caused increased pain without treatment modulation. Following pain and manual intervention, SOR increased baroreflex sensitivity in the 0.15-0.35 Hz range and decreased R-R interval power spectral density in the 0.03-0.5 Hz range compared with yaw. To probe potential mechanisms and interactions between manual treatment and a prototypic analgesic, oral aspirin (967 mg) was given 60 minutes before testing to reduce prostaglandin synthesis. Aspirin slightly attenuated pain but neither altered cardiovascular changes to PEMI nor interacted with SOR or yaw. CONCLUSIONS: SOR has the capacity to modulate pain-induced autonomic control and regulation.

Piezoelectric 3-D Fibrous Poly(3-hydroxybutyrate)-Based Scaffolds Ultrasound-Mineralized with Calcium Carbonate for Bone Tissue Engineering: Inorganic Phase Formation, Osteoblast Cell Adhesion, and Proliferation.

Elaboration of novel biocomposites providing simultaneously both biodegradability and stimulated bone tissue repair is essential for regenerative medicine. In particular, piezoelectric biocomposites are attractive because of a possibility to electrically stimulate cell response. In the present study, novel CaCO3-mineralized piezoelectric biodegradable scaffolds based on two polymers, poly[( R)3-hydroxybutyrate] (PHB) and poly[3-hydroxybutyrate- co-3-hydroxyvalerate] (PHBV), are presented. Mineralization of the scaffold surface is carried out by the in situ synthesis of CaCO3 in the vaterite and calcite polymorphs using ultrasound (U/S). Comparative characterization of PHB and PHBV scaffolds demonstrated an impact of the porosity and surface charge on the mineralization in a dynamic mechanical system, as no essential distinction was observed in wettability, structure, and surface chemical compositions. A significantly higher (4.3 times) piezoelectric charge and a higher porosity (∼15%) lead to a more homogenous CaCO3 growth in 3-D fibrous structures and result in a two times higher relative mass increase for PHB scaffolds compared to that for PHBV. This also increases the local ion concentration incurred upon mineralization under U/S-generated dynamic mechanical conditions. The modification of the wettability for PHB and PHBV scaffolds from hydrophobic (nonmineralized fibers) to superhydrophilic (mineralized fibers) led to a pronounced apatite-forming behavior of scaffolds in a simulated body fluid. In turn, this results in the formation of a dense monolayer of well-distributed and proliferated osteoblast cells along the fibers. CaCO3-mineralized PHBV surfaces had a higher osteoblast cell adhesion and proliferation assigned to a higher amount of CaCO3 on the surface compared to that on PHB scaffolds, as incurred from micro-computed tomography (µCT). Importantly, a cell viability study confirmed biocompatibility of all the scaffolds. Thus, hybrid biocomposites based on the piezoelectric PHB polymers represent an effective scaffold platform functionalized by an inorganic phase and stimulating the growth of the bone tissue.

[18F]-florbetaben PET/CT Imaging in the Alzheimer's Disease Mouse Model APPswe/PS1dE9.

BACKGROUND: Positron-emission-tomography (PET) using 18F labeled florbetaben allows noninvasive in vivo-assessment of amyloid-beta (Aß), a pathological hallmark of Alzheimer's disease (AD). In preclinical research, [18F]-florbetaben-PET has already been used to test the amyloid-lowering potential of new drugs, both in humans and in transgenic models of cerebral amyloidosis. The aim of this study was to characterize the spatial pattern of cerebral uptake of [18F]-florbetaben in the APPswe/ PS1dE9 mouse model of AD in comparison to histologically determined number and size of cerebral Aß plaques. METHODS: Both, APPswe/PS1dE9 and wild type mice at an age of 12 months were investigated by smallanimal PET/CT after intravenous injection of [18F]-florbetaben. High-resolution magnetic resonance imaging data were used for quantification of the PET data by volume of interest analysis. The standardized uptake values (SUVs) of [18F]-florbetaben in vivo as well as post mortem cerebral Aß plaque load in cortex, hippocampus and cerebellum were analyzed. RESULTS: Visual inspection and SUVs revealed an increased cerebral uptake of [18F]-florbetaben in APPswe/ PS1dE9 mice compared with wild type mice especially in the cortex, the hippocampus and the cerebellum. However, SUV ratios (SUVRs) relative to cerebellum revealed only significant differences in the hippocampus between the APPswe/PS1dE9 and wild type mice but not in cortex; this differential effect may reflect the lower plaque area in the cortex than in the hippocampus as found in the histological analysis. CONCLUSION: The findings suggest that histopathological characteristics of Aß plaque size and spatial distribution can be depicted in vivo using [18F]-florbetaben in the APPswe/PS1dE9 mouse model.

Altered stimulus representation in rat auditory cortex is not causal for loss of consciousness under general anaesthesia.

BACKGROUND: Current concepts suggest that impaired representation of information in cortical networks contributes to loss of consciousness under anaesthesia. We tested this idea in rat auditory cortex using information theory analysis of multiunit responses recorded under three anaesthetic agents with different molecular targets: isoflurane, propofol, and dexmedetomidine. We reasoned that if changes in the representation of sensory stimuli are causal for loss of consciousness, they should occur regardless of the specific anaesthetic agent. METHODS: Spiking responses were recorded with chronically implanted microwire arrays in response to acoustic stimuli incorporating varied temporal and spectral dynamics. Experiments consisted of four drug conditions: awake (pre-drug), sedation (i.e. intact righting reflex), loss of consciousness (a dose just sufficient to cause loss of righting reflex), and recovery. Measures of firing rate, spike timing, and mutual information were analysed as a function of drug condition. RESULTS: All three drugs decreased spontaneous and evoked spiking activity and modulated spike timing. However, changes in mutual information were inconsistent with altered stimulus representation being causal for loss of consciousness. First, direction of change in mutual information was agent-specific, increasing under dexmedetomidine and decreasing under isoflurane and propofol. Second, mutual information did not decrease at the transition between sedation and LOC for any agent. Changes in mutual information under anaesthesia correlated strongly with changes in precision and reliability of spike timing, consistent with the importance of temporal stimulus features in driving auditory cortical activity. CONCLUSIONS: The primary sensory cortex is not the locus for changes in representation of information causal for loss of consciousness under anaesthesia.

Decitabine demonstrates antileukemic activity in B cell precursor acute lymphoblastic leukemia with MLL rearrangements.

BACKGROUND: Promotor hypermethylation of CpG islands is common in B cell precursor acute lymphoblastic leukemia (BCP-ALL) with mixed lineage leukemia (MLL) gene rearrangements. Hypomethylating agents (HMA) such as azacitidine (AZA) and decitabine (DEC) reduce DNA hypermethylation by incorporation into DNA and were successfully introduced into the clinic for the treatment of myeloid neoplasias. METHODS: Here, we investigated whether HMA induce comparable biological effects in MLL-positive BCP-ALL. Further, efficacy of HMA and concomitant application of cytostatic drugs (cytarabine and doxorubicin) were evaluated on established SEM and RS4;11 cell lines. In addition, promising approaches were studied on BCP-ALL cell line- and patient-derived xenograft models. RESULTS: In general, DEC effects were stronger compared to AZA on MLL-positive BCP-ALL cells. DEC significantly reduced proliferation by induction of cell cycle arrest in G0/G1 phase and apoptosis. Most sensitive to HMA were SEM cells which are characterized by a fast cell doubling time. The combination of low-dose HMA and conventional cytostatic agents revealed a heterogeneous response pattern. The strongest antiproliferative effects were observed when ALL cells were simultaneously exposed to HMA and cytostatic drugs. Most potent synergistic effects of HMA were induced with cytarabine. Finally, the therapeutic potential of DEC was evaluated on BCP-ALL xenograft models. DEC significantly delayed leukemic proliferation in xenograft models as demonstrated longitudinally by non-invasive bioluminescence as well as 18F-FDG-PET/CT imaging. Unexpectedly, in vivo concomitant application of DEC and cytarabine did not enhance the antiproliferative effect compared to DEC monotherapy. CONCLUSIONS: Our data reveal that DEC is active in MLL-positive BCP-ALL and warrant clinical evaluation.

External radiation exposure, excretion, and effective half-life in 177Lu-PSMA-targeted therapies.

BACKGROUND: Prostate-specific membrane antigen (PSMA)-targeted therapy with 177Lu-PSMA-617 is a therapeutic option for patients with metastatic castration-resistant prostate cancer (mCRPC). To optimize the therapy procedure, it is necessary to determine relevant parameters to define radiation protection and safety necessities. Therefore, this study aimed at estimating the ambient radiation exposure received by the patient. Moreover, the excreted activity was quantified. RESULTS: In total, 50 patients with mCRPC and treated with 177Lu-PSMA-617 (mean administered activity 6.3 ± 0.5 GBq) were retrospectively included in a bi-centric study. Whole-body dose rates were measured at a distance of 2 m at various time points after application of 177Lu-PSMA-617, and effective half-lives for different time points were calculated and compared. Radiation exposure to the public was approximated using the dose integral. For the estimation of the excreted activity, whole body measurements of 25 patients were performed at 7 time points. Unbound 177Lu-PSMA-617 was rapidly cleared from the body. After 4 h, approximately 50% and, after 12 h, approximately 70% of the administered activity were excreted, primarily via urine. The mean dose rates were the following: 3.6 ± 0.7 µSv/h at 2 h p. i., 1.6 ± 0.6 µSv/h at 24 h, 1.1 ± 0.5 µSv/h at 48 h, and 0.7 ± 0.4 µSv/h at 72 h. The mean effective half-life of the cohort was 40.5 ± 9.6 h (min 21.7 h; max 85.7 h). The maximum dose to individual members of the public per treatment cycle was ~ 250 ± 55 µSv when the patient was discharged from the clinic after 48 h and ~ 190 ± 36 µSv when the patient was discharged after 72 h. CONCLUSIONS: In terms of the radiation exposure to the public, 177Lu-PSMA is a safe option of radionuclide therapy. As usually four (sometimes more) cycles of the therapy are performed, it must be conducted in a way that ensures that applicable legal requirements can be followed. In other words, the radiation exposure to the public and the concentration of activity in wastewater must be sub-marginal. Therefore, in certain countries, hospitalization of these patients is mandatory.

[Somatostatin receptor PET/CT (SSTR-PET/CT)]. / Somatostatinrezeptor-PET/CT.

The present guideline is focused on quality assurance of somatostatin receptor PET/CT (SSTR-PET/CT) in oncology patients. The document has been developed by a multidisciplinary board of specialists providing consensus of definitions, prerequisites, methodology, operating procedures, assessment, and standardized reporting. In particular, imaging procedures for the two most commonly used radioligands of human SSTR, i. e. 68Ga-DOTATOC and 68Ga-DOTATATE are presented. Overall, SSTR-PET/CT requires close interdisciplinary communication and cooperation of referring and executing medical disciplines, taking into account existing guidelines and recommendations of the European and German medical societies, including the European Association of Nuclear Medicine (EANM), German Society for Endocrinology (DGE), German Society for Nuclear Medicine (DGN) and German Society for Radiology (DRG).

Characterization of aluminum, aluminum oxide and titanium dioxide nanomaterials using a combination of methods for particle surface and size analysis.

The application of appropriate analytical techniques is essential for nanomaterial (NM) characterization. In this study, we compared different analytical techniques for NM analysis. Regarding possible adverse health effects, ionic and particulate NM effects have to be taken into account. As NMs behave quite differently in physiological media, special attention was paid to techniques which are able to determine the biosolubility and complexation behavior of NMs. Representative NMs of similar size were selected: aluminum (Al0) and aluminum oxide (Al2O3), to compare the behavior of metal and metal oxides. In addition, titanium dioxide (TiO2) was investigated. Characterization techniques such as dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) were evaluated with respect to their suitability for fast characterization of nanoparticle dispersions regarding a particle's hydrodynamic diameter and size distribution. By application of inductively coupled plasma mass spectrometry in the single particle mode (SP-ICP-MS), individual nanoparticles were quantified and characterized regarding their size. SP-ICP-MS measurements were correlated with the information gained using other characterization techniques, i.e. transmission electron microscopy (TEM) and small angle X-ray scattering (SAXS). The particle surface as an important descriptor of NMs was analyzed by X-ray diffraction (XRD). NM impurities and their co-localization with biomolecules were determined by ion beam microscopy (IBM) and confocal Raman microscopy (CRM). We conclude advantages and disadvantages of the different techniques applied and suggest options for their complementation. Thus, this paper may serve as a practical guide to particle characterization techniques.

Correction to: 18F-NaF PET/CT: EANM procedure guidelines for bone imaging.

The original version of this article unfortunately contained an error. The name and affiliation of "Frédéric Paycha" needs to be corrected. Given in this article is the correct author name and affiliation.

Disruption of cortical network activity by the general anaesthetic isoflurane.

BACKGROUND: Actions of general anaesthetics on activity in the cortico-thalamic network likely contribute to loss of consciousness and disconnection from the environment. Previously, we showed that the general anaesthetic isoflurane preferentially suppresses cortically evoked synaptic responses compared with thalamically evoked synaptic responses, but how this differential sensitivity translates into changes in network activity is unclear. METHODS: We investigated isoflurane disruption of spontaneous and stimulus-induced cortical network activity using multichannel recordings in murine auditory thalamo-cortical brain slices. RESULTS: Under control conditions, afferent stimulation elicited short latency, presumably monosynaptically driven, spiking responses, as well as long latency network bursts that propagated horizontally through the cortex. Isoflurane (0.05-0.6 mM) suppressed spiking activity overall, but had a far greater effect on network bursts than on early spiking responses. At isoflurane concentrations >0.3 mM, network bursts were almost entirely blocked, even with increased stimulation intensity and in response to paired (thalamo-cortical + cortical layer 1) stimulation, while early spiking responses were <50% blocked. Isoflurane increased the threshold for eliciting bursts, decreased their propagation speed and prevented layer 1 afferents from facilitating burst induction by thalamo-cortical afferents. CONCLUSIONS: Disruption of horizontal activity spread and of layer 1 facilitation of thalamo-cortical responses likely contribute to the mechanism by which suppression of cortical feedback connections disrupts sensory awareness under anaesthesia.

Medial frontal GABA is lower in older schizophrenia: a MEGA-PRESS with macromolecule suppression study.

Gamma-butyric acid (GABA) dysfunction has been implicated in the pathophysiology of schizophrenia and its cognitive deficits. Proton magnetic resonance spectroscopy (MRS) was used to test the hypothesis that older participants with schizophrenia have lower anterior cingulate GABA levels compared with older control participants. One-hundred forty-five participants completed this study. For detection of GABA, spectra were acquired from the medial frontal/anterior cingulate cortex using a macromolecule-suppressed MEGA-PRESS sequence. Patients were evaluated for psychopathology and all participants completed neuropsychological tests of working memory, processing speed and functional capacity. GABA levels were significantly lower in the older participants with schizophrenia (n=31) compared with the older control (n=37) group (P=0.003) but not between the younger control (n=40) and schizophrenia (n=29) groups (P=0.994). Age strongly predicted GABA levels in the schizophrenia group accounting for 42% of the variance, but the effect of age was less in the control group accounting for 5.7% of the variance. GABA levels were specifically related to working memory but not processing speed performance, functional capacity, or positive or negative symptom severity. This is the largest MRS study of GABA in schizophrenia and the first to examine GABA without macromolecule contamination, a potentially significant issue in previous studies. GABA levels more rapidly declined with advancing age in the schizophrenia compared with the control group. Interventions targeted at halting the decline or increasing GABA levels may improve functional outcomes and quality of life as patients with schizophrenia age.

Pre-gestational overweight in guinea pig sows induces fetal vascular dysfunction and increased rate of large and small fetuses.

In humans, obesity before and during pregnancy is associated with both fetal macrosomia and growth restriction, and long-term cardiovascular risk in the offspring. We aimed to determine whether overweighted pregnant guinea pig sows results in an increased fetal weight at term and the effects on the vascular reactivity in fetal systemic and umbilical arteries. Pregnant guinea pigs were classified as control (n=4) or high weight (HWS, n=5) according to their pre-mating weight, and their fetuses extracted at 0.9 gestation (~60 days). Segments of fetal femoral and umbilical arteries were mounted in a wire myograph, where the contractile response to KCl (5-125 mM), and the relaxation to nitric oxide synthase-dependent agents (insulin, 10-10-10-7 and acetylcholine, 10-10-10-5) and nitric oxide [sodium nitroprusside (SNP), 10-10-10-5] were determined. Fetuses from HWS (HWSF) were grouped according to their body weight as low (85 g) fetal weight, based on the confidence interval (76.5-84.9 g) of the control group. No HWSF were observed in the normal range. Umbilical arteries from HWSF showed a lower response to KCl and insulin compared with controls, but a comparable response with SNP. Conversely, femoral arteries from HWSF showed an increased response to KCl and acetylcholine, along with a decreased sensitivity to SNP. These data show that overweight sows have altered fetal growth along gestation. Further, large and small fetuses from obese guinea pig sows showed altered vascular reactivity at umbilical and systemic vessels, which potentially associates with long-term cardiovascular risk.

(18)F-NaF PET/CT: EANM procedure guidelines for bone imaging.

The aim of this guideline is to provide minimum standards for the performance and interpretation of (18)F-NaF PET/CT scans. Standard acquisition and interpretation of nuclear imaging modalities will help to provide consistent data acquisition and numeric values between different platforms and institutes and to promote the use of PET/CT modality as an established diagnostic modality in routine clinical practice. This will also improve the value of scientific work and its contribution to evidence-based medicine.

Oxidative stress as common trait of endothelial dysfunction in chorionic arteries from fetuses with IUGR and LGA.

INTRODUCTION: Fetal macrosomia and intrauterine growth restriction (IUGR) associate with increased morbidity in the neonate. Placental vascular relaxation is impaired in fetal macrosomia, as well as in IUGR, and this could result from increased oxidative stress present in both conditions. We determined the role of pro- and anti-oxidants on NOS dependent relaxation in placental chorionic arteries from pregnancies with LGA babies from overweight and/or obese mothers (LOOM) and IUGR fetuses from normal BMI women. METHODS: Chorionic arteries were mounted in a wire-myograph, where responses to the NOS-dependent agent CGRP in presence or absence of the antioxidant N-acetyl cysteine (NAC), the pro-oxidant SIN-1, the SOD inhibitor DDC, and the GPx inhibitor MS were determined. Additionally the presence of pro- and antioxidant enzymes (NOX-4, SOD-1, SOD-2 and GPx-1) and eNOS in chorionic and umbilical vessels were addressed by immunohistochemistry. RESULTS: Maximal CGRP-induced relaxation was comparable to controls but presented a reduced potency in chorionic arteries from LOOM placentae, whilst in IUGR vessels both maximal response and potency were reduced. NAC increased maximal relaxation in controls, IUGR and LOOM arteries, whilst SIN-1 completely abolished the CGRP-induced relaxation only in IUGR and LOOM samples, the later effect was paralleled by SOD or GPx inhibition. These responses associated with the presence of NOX-4, SOD-1 and GPx-1 in the endothelium and vascular wall of chorionic and umbilical arteries in the different groups studied. DISCUSSION: These data suggest that NOS dependent relaxation in placental vessels from IUGR and LOOM pregnancies present a higher sensitivity to oxidative stress.

[How to write a good clinical review?]. / Wie schreibe ich eine gute Übersichtsarbeit?

Clinical reviews are an important part of the medical literature offering the reader condensed information on a specific topic. In radiology and nuclear medicine most clinical reviews have a subjective character as they have been written in a rather narrative way. Based on their low level of evidence these narrative reviews are frequently not being considered for establishment of clinical guidelines. The aim of this paper is to aid the reader in writing a good clinical review by highlighting the different aspects of a systematic review.

[Peptide receptor radionuclide therapy for patients with somatostatin receptor expressing tumours. German Guideline (S1)]. / Peptidrezeptor-Radionuklidtherapie Somatostatinrezeptor-exprimierender Tumore. DGN-Leitlinie (S1).

This document describes the guideline for peptide receptor radionuclide therapy (PRRT) published by the German Society of Nuclear Medicine (DGN) and accepted by the Association of the Scientific Medical Societies in Germany (AWMF) to be included in the official AWMF Guideline Registry. These recommendations are a prerequisite for the quality management in the treatment of patients with somatostatin receptor expressing tumours using PRRT. They are aimed at guiding nuclear medicine specialists in selecting likely candidates to receive PRRT and to deliver the treatment in a safe and effective manner. The recommendations are based on an interdisciplinary consensus. The document contains background information and definitions and covers the rationale, indications and contraindications for PRRT. Essential topics are the requirements for institutions performing the therapy, e. g. presence of an expert for medical physics, intense cooperation with all colleagues involved in the treatment of a patient, and a certificate of instruction in radiochemical labelling and quality control are required. Furthermore, it is specified which patient data have to be available prior to performance of therapy and how treatment has to be carried out technically. Here, quality control and documentation of labelling are of great importance. After treatment, clinical quality control is mandatory (work-up of therapy data and follow-up of patients). Essential elements of follow-up are specified in detail. The complete treatment inclusive after-care has to be realised in close cooperation with the involved medical disciplines. Generally, the decision for PRRT should be undertaken within the framework of a multi-disciplinary tumour board.