The role of metabotropic glutamate receptor 5 in the pathogenesis of mood disorders and addiction: combining preclinical evidence with human Positron Emission Tomography (PET) studies.

In the present review, we deliver an overview of the involvement of metabotropic glutamate receptor 5 (mGluR5) activity and density in pathological anxiety, mood disorders and addiction. Specifically, we will describe mGluR5 studies in humans that employed Positron Emission Tomography (PET) and combined the findings with preclinical animal research. This combined view of different methodological approaches-from basic neurobiological approaches to human studies-might give a more comprehensive and clinically relevant view of mGluR5 function in mental health than the view on preclinical data alone. We will also review the current research data on mGluR5 along the Research Domain Criteria (RDoC). Firstly, we found evidence of abnormal glutamate activity related to the positive and negative valence systems, which would suggest that antagonistic mGluR5 intervention has prominent anti-addictive, anti-depressive and anxiolytic effects. Secondly, there is evidence that mGluR5 plays an important role in systems for social functioning and the response to social stress. Finally, mGluR5's important role in sleep homeostasis suggests that this glutamate receptor may play an important role in RDoC's arousal and modulatory systems domain. Glutamate was previously mostly investigated in non-human studies, however initial human clinical PET research now also supports the hypothesis that, by mediating brain excitability, neuroplasticity and social cognition, abnormal metabotropic glutamate activity might predispose individuals to a broad range of psychiatric problems.

Development and Test of a Neutron Imaging Setup at the PGAA Instrument at FRM II

We report on the developments of a neutron tomography setup at the instrument for prompt gamma-ray activation analysis (PGAA) at the Maier-Leibnitz Zentrum(MLZ). The recent developments are driven by the idea of combining the spatial information obtained with neutron tomography with the elemental information determined with PGAA, i.e. to further combine both techniques to an investigative technique called prompt gamma activation imaging (PGAI).At the PGAA instrument, a cold neutron flux of up to 6 x 1010 cm-2 s-1 (thermal equivalent) is available in the focus of an elliptically tapered neutron guide. In the reported experiments, the divergence of the neutron beam was investigated, the resolution of the installed detector system tested, and a proof-of-principle tomography experiment performed. In our study a formerly used camera box was upgraded with a better camera and an optical resolution of 8 line pairs/mm was achieved. The divergence of the neutron beam was measured by a systematic scan along the beam axis. Based on the acquired data, a neutron imaging setup with a L/D ratio of 200 was installed. The resolution of the setup was testedin combination with a gadolinium test target and different scintillator screens. The test target was irradiated at two positions to determine the maximum resolution and the resolution at the actual sample position. The performance of the installed tomography setup was demonstrated bya tomography experiment of an electric amplifier tube.

MEMLS3&a: Microwave Emission Model of Layered Snowpacks adapted to include backscattering

The Microwave Emission Model of Layered Snowpacks (MEMLS) was originally developed for microwave emissions of snowpacks in the frequency range 5–100 GHz. It is based on six-flux theory to describe radiative transfer in snow including absorption, multiple volume scattering, radiation trapping due to internal reflection and a combination of coherent and incoherent superposition of reflections between horizontal layer interfaces. Here we introduce MEMLS3&a, an extension of MEMLS, which includes a backscatter model for active microwave remote sensing of snow. The reflectivity is decomposed into diffuse and specular components. Slight undulations of the snow surface are taken into account. The treatment of like- and cross-polarization is accomplished by an empirical splitting parameter q. MEMLS3&a (as well as MEMLS) is set up in a way that snow input parameters can be derived by objective measurement methods which avoid fitting procedures of the scattering efficiency of snow, required by several other models. For the validation of the model we have used a combination of active and passive measurements from the NoSREx (Nordic Snow Radar Experiment) campaign in Sodankylä, Finland. We find a reasonable agreement between the measurements and simulations, subject to uncertainties in hitherto unmeasured input parameters of the backscatter model. The model is written in Matlab and the code is publicly available for download through the following website: http://www.iapmw.unibe.ch/research/projects/snowtools/memls.html.

Positron emission mammography in the diagnosis of breast cancer. Is maximum PEM uptake value a valuable threshold for malignant breast cancer detection?

AIM To evaluate the diagnostic value (sensitivity, specificity) of positron emission mammography (PEM) in a single site non-interventional study using the maximum PEM uptake value (PUVmax). PATIENTS, METHODS In a singlesite, non-interventional study, 108 patients (107 women, 1 man) with a total of 151 suspected lesions were scanned with a PEM Flex Solo II (Naviscan) at 90 min p.i. with 3.5 MBq 18F-FDG per kg of body weight. In this ROI(region of interest)-based analysis, maximum PEM uptake value (PUV) was determined in lesions, tumours (PUVmaxtumour), benign lesions (PUVmaxnormal breast) and also in healthy tissues on the contralateral side (PUVmaxcontralateral breast). These values were compared and contrasted. In addition, the ratios of PUVmaxtumour / PUVmaxcontralateral breast and PUVmaxnormal breast / PUVmaxcontralateral breast were compared. The image data were interpreted independently by two experienced nuclear medicine physicians and compared with histology in cases of suspected carcinoma. RESULTS Based on a criteria of PUV>1.9, 31 out of 151 lesions in the patient cohort were found to be malignant (21%). A mean PUVmaxtumour of 3.78 ± 2.47 was identified in malignant tumours, while a mean PUVmaxnormal breast of 1.17 ± 0.37 was reported in the glandular tissue of the healthy breast, with the difference being statistically significant (p < 0.001). Similarly, the mean ratio between tumour and healthy glandular tissue in breast cancer patients (3.15 ± 1.58) was found to be significantly higher than the ratio for benign lesions (1.17 ± 0.41, p < 0.001). CONCLUSION PEM is capable of differentiating breast tumours from benign lesions with 100% sensitivity along with a high specificity of 96%, when a threshold of PUVmax >1.9 is applied.

Final Results of a Prospective Evaluation of the Predictive Value of Interim Positron Emission Tomography in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP-14 (SAKK 38/07)

PURPOSE Our main objective was to prospectively determine the prognostic value of [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) after two cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone given every 14 days (R-CHOP-14) under standardized treatment and PET evaluation criteria. PATIENTS AND METHODS Patients with any stage of diffuse large B-cell lymphoma were treated with six cycles of R-CHOP-14 followed by two cycles of rituximab. PET/CT examinations were performed at baseline, after two cycles (and after four cycles if the patient was PET-positive after two cycles), and at the end of treatment. PET/CT examinations were evaluated locally and by central review. The primary end point was event-free survival at 2 years (2-year EFS). RESULTS Median age of the 138 evaluable patients was 58.5 years with a WHO performance status of 0, 1, or 2 in 56%, 36%, or 8% of the patients, respectively. By local assessment, 83 PET/CT scans (60%) were reported as positive and 55 (40%) as negative after two cycles of R-CHOP-14. Two-year EFS was significantly shorter for PET-positive compared with PET-negative patients (48% v 74%; P = .004). Overall survival at 2 years was not significantly different, with 88% for PET-positive versus 91% for PET-negative patients (P = .46). By using central review and the Deauville criteria, 2-year EFS was 41% versus 76% (P < .001) for patients who had interim PET/CT scans after two cycles of R-CHOP-14 and 24% versus 72% (P < .001) for patients who had PET/CT scans at the end of treatment. CONCLUSION Our results confirmed that an interim PET/CT scan has limited prognostic value in patients with diffuse large B-cell lymphoma homogeneously treated with six cycles of R-CHOP-14 in a large prospective trial. At this point, interim PET/CT scanning is not ready for clinical use to guide treatment decisions in individual patients.

Molecular-Based Magnetism in Bimetallic Two-Dimensional Oxalate-Bridged Networks. An X-ray and Neutron Diffraction Study

Bimetallic, oxalate-bridged compounds with bi- and trivalent transition metals comprise a class of layered materials which express a large variety in their molecular-based magnetic behavior. Because of this, the availability of the corresponding single-crystal structural data is essential to the successful interpretation of the experimental magnetic results. We report in this paper the crystal structure and magnetic properties of the ferromagnetic compound {[N(n-C3H7)4][MnIICrIII(C2O4)3]}n (1), the crystal structure of the antiferromagnetic compound {[N(n-C4H9)4][MnIIFeIII(C2O4)3]}n (2), and the results of a neutron diffraction study of a polycrystalline sample of the ferromagnetic compound {[P(C6D5)4][MnIICrIII(C2O4)3]}n (3). Crystal data:  1, rhombohedral, R3c, a = 9.363(3) Å, c = 49.207(27) Å, Z = 6; 2, hexagonal, P63, a = 9.482(2) Å, c = 17.827(8) Å, Z = 2. The structures consist of anionic, two-dimensional, honeycomb networks formed by the oxalate-bridged metal ions, interleaved by the templating cations. Single-crystal field dependent magnetization measurements as well as elastic neutron scattering experiments on the manganese(II)−chromium(III) samples show the existence of long-range ferromagnetic ordering behavior below Tc = 6 K. The magnetic structure corresponds to an alignment of the spins perpendicular to the network layers. In contrast, the manganese(II)−iron(III) compound expresses a two-dimensional antiferromagnetic ordering.

New Clinical Indications for (18)F/(11)C-choline, New Tracers for Positron Emission Tomography and a Promising Hybrid Device for Prostate Cancer Staging: A Systematic Review of the Literature

CONTEXT Radiolabelled choline positron emission tomography has changed the management of prostate cancer patients. However, new emerging radiopharmaceutical agents, like radiolabelled prostate specific membrane antigen, and new promising hybrid imaging will begin new challenges in the diagnostic field. OBJECTIVE The continuous evolution in nuclear medicine has led to the improvement in the detection of recurrent prostate cancer (PCa), particularly distant metastases. New horizons have been opened for radiolabelled choline positron emission tomography (PET)/computed tomography (CT) as a guide for salvage therapy or for the assessment of systemic therapies. In addition, new tracers and imaging tools have been recently tested, providing important information for the management of PCa patients. Herein we discuss: (1) the available evidence in literature on radiolabelled choline PET and their recent indications, (2) the role of alternative radiopharmaceutical agents, and (3) the advantages of a recent hybrid imaging device (PET/magnetic resonance imaging) in PCa. EVIDENCE ACQUISITION Data from recently published (2010-2015), original articles concerning the role of choline PET/CT, new emerging radiotracers, and a new imaging device are analysed. This review is reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. EVIDENCE SYNTHESIS In the restaging phase, the detection rate of choline PET varies between 4% and 97%, mainly depending on the site of recurrence and prostate-specific antigen levels. Both 68gallium (68Ga)-prostate specific membrane antigen and 18F-fluciclovine are shown to be more accurate in the detection of recurrent disease as compared with radiolabelled choline PET/CT. Particularly, Ga68-PSMA has a detection rate of 50% and 68%, respectively for prostate-specific antigen levels < 0.5ng/ml and 0.5-2ng/ml. Moreover, 68Ga- PSMA PET/magnetic resonance imaging demonstrated a particularly higher accuracy in detecting PCa than PET/CT. New tracers, such as radiolabelled bombesin or urokinase-type plasminogen activator receptor, are promising, but few data in clinical practice are available today. CONCLUSIONS Some limitations emerge from the published papers, both for radiolabelled choline PET/CT and also for new radiopharmaceutical agents. Efforts are still needed to enhance the impact of published data in the world of oncology, in particular when new radiopharmaceuticals are introduced into the clinical arena. PATIENT SUMMARY In the present review, the authors summarise the last evidences in clinical practice for the assessment of prostate cancer, by using nuclear medicine modalities, like positron emission tomography/computed tomography and positron emission tomography/magnetic resonance imaging.