Therapeutic Radiometals: Global Trends Analysis of Scientific Literature (2008 -2018)

Background-aim: Academic journals have published a large number of papers in the therapeutic NM research field in the last 10 years. Despite this, a literature analysis has never been made before to point out the research interest in therapeutic radionuclides (RNs). For this reason, the present study has the aim to specifically analyze the research output on therapeutic radiometals from 2008 (January) to 2018 (October) with the aim to quantify and identify the global trend of scientific literature and emphasize the interdisciplinary nature of this research field. Methods: The data search has been targeted on conventional (I-131, Y-90, Lu-177, Re-188, Re-186, Sm-153, Sr-89, Er-186) and emergent (Cu-67, Sc-47, Ra-223, Ho-166, Tb-161, Tb-149, Pb-212/Bi-212, Ac225, Bi-213, At-211, Sn-117) RNs. Authors, starting from this time frame data, have been quantitatively first, and qualitatively after, analyzed and interpreted the scientific trend of this topic. Bibliometric data have been exported from Scopus database and elaborated with Excel. The number of article, article in press, note, short survey, review and letter, have been divided per year and RN with the aim to make perceptible the trend of the last decade. Data have been categorized also in terms of Journal Subject Areas in order to bring out the multidisciplinary nature of the research in this field. Finally, for each publication, authors country provenience have been extrapolated and elaborated to map the global researcher interest and involvement of human and financial resources. Results: A total of 12.717 publications have been analyzed. 81.3% of the publications regards conventional RNs while 18.7% regards emergent RNs. The most investigated therapeutic RNs are I-131, Y-90, Lu-177 among conventional, Ra-223, followed by Sn-117, Bi213 and Ac-225 among emergent RNs. From the analysis, it is evident the multidisciplinary contribution to this field but in particular, as expected, in the case of conventional RN most publications comes from preclinical and clinical fields while for the emergents the contribution is unbalanced for Physics, Engineering, Material Science fields mainly focused on emergent RNs production studies. From the geographical point of view we can see how almost half of the total works have been published by European in both conventional and Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S127 123 emergent RNs categories. It is also evident the high collaboration grade between countries characteristics in line with the multidisciplinarity of this medical sector. Moreover, we extrapolated a countries top 20 for each category. On the podium for the conventional RNs are USA, Germany and China, while for emergent RNs are USA, Germany, United Kingdom. And much more. Conclusions: From this analysis arise that the success of NM has been intimately linked to the availability of new RNs and the radiopharmaceuticals field is constantly evolving thanks to the contribution of specialists coming from different disciplines and the collaboration between countries. In recent years the focus of the research shifted on the field of emergent therapeutic radioisotope production and application, such as Cu-67, Sc-47, for the interest in new treatment strategies such as the theranostics personalized approach. Alpha emitters, in particular Ra-223 and Ac-225 are also gaining attention in particular in USA and Germany. Instead, among conventional radionuclides the research on Lu-177 is constantly growing

Field effect enhancement in buffered quantum nanowire networks

III-V semiconductor nanowires have shown great potential in various quantum transport experiments. However, realizing a scalable high-quality nanowire-based platform that could lead to quantum information applications has been challenging. Here, we study the potential of selective area growth by molecular beam epitaxy of InAs nanowire networks grown on GaAs-based buffer layers. The buffered geometry allows for substantial elastic strain relaxation and a strong enhancement of field effect mobility. We show that the networks possess strong spin-orbit interaction and long phase coherence lengths with a temperature dependence indicating ballistic transport. With these findings, and the compatibility of the growth method with hybrid epitaxy, we conclude that the material platform fulfills the requirements for a wide range of quantum experiments and applications

Radioisotopic purity and imaging properties of cyclotron-produced 99mTc using direct 100Mo(p,2n) reaction

Evaluation of the radioisotopic purity of technetium-99m (99mTc) produced in GBq amounts by proton bombardment of enriched molibdenum-100 (100Mo) metallic targets at low proton energies (i.e. within 15\u201320 MeV) is conducted. This energy range was chosen since it is easily achievable by many conventional medical cyclotrons already available in the nuclear medicine departments of hospitals. The main motivation for such a study is in the framework of the research activities at the international level that have been conducted over the last few years to develop alternative production routes for the most widespread radioisotope used in medical imaging. The analysis of technetium isotopes and isomeric states (9xTc) present in the pertechnetate saline Na99mTcO4 solutions, obtained after the extraction/purification procedure, reveals radionuclidic purity levels basically in compliance with the limits recently issued by European Pharmacopoeia 9.3 (2018 Sodium pertechnetate (99mTc) injection 4801\u20133). Moreover, the impact of 9xTc contaminant nuclides on the final image quality is thoroughly evaluated, analyzing the emitted high-energy gamma rays and their influence on the image quality. The spatial resolution of images from cyclotron-produced 99mTc acquired with a mini-gamma camera was determined and compared with that obtained using technetium-99m solutions eluted from standard 99Mo/99mTc generators. The effect of the increased image background contribution due to Compton-scattered higher-energy gamma rays (E \u3b3 \u2009\u2009>\u2009\u2009200\u2009keV), which could cause image-contrast deterioration, was also studied. It is concluded that, due to the high radionuclidic purity of cyclotron-produced 99mTc using 100Mo(p,2n)99mTc reaction at a proton beam energy in the range 15.7\u201319.4 MeV, the resulting image properties are well comparable with those from the generator-eluted 99mTc

Detrimental and protective action of microglial extracellular vesicles on myelin lesions: astrocyte involvement in remyelination failure

Microglia are highly plastic immune cells which exist in a continuum of activation states. By shaping the function of oligodendrocyte precursor cells (OPCs), the brain cells which differentiate to myelin-forming cells, microglia participate in both myelin injury and remyelination during multiple sclerosis. However, the mode(s) of action of microglia in supporting or inhibiting myelin repair is still largely unclear. Here, we analysed the effects of extracellular vesicles (EVs) produced in vitro by either pro-inflammatory or pro-regenerative microglia on OPCs at demyelinated lesions caused by lysolecithin injection in the mouse corpus callosum. Immunolabelling for myelin proteins and electron microscopy showed that EVs released by pro-inflammatory microglia blocked remyelination, whereas EVs produced by microglia co-cultured with immunosuppressive mesenchymal stem cells promoted OPC recruitment and myelin repair. The molecular mechanisms responsible for the harmful and beneficial EV actions were dissected in primary OPC cultures. By exposing OPCs, cultured either alone or with astrocytes, to inflammatory EVs, we observed a blockade of OPC maturation only in the presence of astrocytes, implicating these cells in remyelination failure. Biochemical fractionation revealed that astrocytes may be converted into harmful cells by the inflammatory EV cargo, as indicated by immunohistochemical and qPCR analyses, whereas surface lipid components of EVs promote OPC migration and/or differentiation, linking EV lipids to myelin repair. Although the mechanisms through which the lipid species enhance OPC maturation still remain to be fully defined, we provide the first demonstration that vesicular sphingosine 1 phosphate stimulates OPC migration, the first fundamental step in myelin repair. From this study, microglial EVs emerge as multimodal and multitarget signalling mediators able to influence both OPCs and astrocytes around myelin lesions, which may be exploited to develop novel approaches for myelin repair not only in multiple sclerosis, but also in neurological and neuropsychiatric diseases characterized by demyelination

A randomized, placebo-controlled phase 2 trial of laquinimod in primary progressive multiple sclerosis

OBJECTIVE: To evaluate efficacy, safety, and tolerability of laquinimod in patients with primary progressive multiple sclerosis (PPMS). METHODS: In the randomized, double-blind, placebo-controlled, phase 2 study ARPEGGIO (A Randomized Placebo-controlled trial Evaluating laquinimod in PPMS, Gauging Gradations In MRI and clinical Outcomes), eligible PPMS patients were randomized 1:1:1 to receive once-daily oral laquinimod 0.6 mg or 1.5 mg or matching placebo. Percentage brain volume change (PBVC; primary endpoint) from baseline to week 48 was assessed by MRI. Secondary and exploratory endpoints included clinical and MRI measures. Efficacy endpoints were evaluated using a predefined, hierarchical statistical testing procedure. Safety was monitored throughout the study. The laquinimod 1.5 mg dose arm was discontinued on January 1, 2016 due to findings of cardiovascular events. RESULTS: 374 patients were randomized to laquinimod 0.6 mg (n = 139) or 1.5 mg (n = 95) or placebo (n = 140). ARPEGGIO did not meet the primary endpoint of significant treatment effect with laquinimod 0.6 mg versus placebo on PBVC from baseline to week 48 (adjusted mean difference = 0.016%, p = 0.903). Laquinimod 0.6 mg reduced the number of new T2 brain lesions at week 48 (risk ratio = 0.4; 95% confidence interval, 0.26-0.69; p = 0.001). Incidence of adverse events was higher among patients treated with laquinimod 0.6 mg (83%) versus laquinimod 1.5 mg (66%) and placebo (78%). CONCLUSIONS: Laquinimod 0.6 mg did not demonstrate a statistically significant effect on brain volume loss in PPMS at week 48

Charge carrier generation, relaxation, and recombination in polytypic GaAs nanowires studied by photoluminescence excitation spectroscopy

We report results of a study of polytypic GaAs nanowires using low-temperature photoluminescence excitation spectroscopy. The nanowire ensemble shows a strong absorption at 1.517 eV, as a result of resonant generation of heavy-hole excitons in the zinc-blende segments of the nanowires. Excitons then diffuse along the length of the nanowire and are trapped by the type-II quantum discs arising from the zinc-blende/ wurtzite crystal structure alternation and recombine radiatively. Finally, experiments on single nanowires demonstrate that the energy of the Gamma(7) conduction band to Gamma(9) valence band exciton of wurtzite GaAs is 1.521 eV at 4K. (C) 2013 AIP Publishing LLC

The visibility of IQHE at sharp edges: Experimental proposals based on interactions and edge electrostatics

The influence of the incompressible strips on the integer quantized Hall effect (IQHE) is investigated, considering a cleaved-edge overgrown (CEO) sample as an experimentally realizable sharp edge system. We propose a set of experiments to clarify the distinction between the large-sample limit when bulk disorder defines the IQHE plateau width and the small-sample limit smaller than the disorder correlation length, when self-consistent edge electrostatics define the IQHE plateau width. The large-sample or bulk QH regime is described by the usual localization picture, whereas the small-sample or edge regime is discussed within the compressible/incompressible strips picture, known as the screening theory of QH edges. Utilizing the unusually sharp edge profiles of the CEO samples, a Hall bar design is proposed to manipulate the edge potential profile from smooth to extremely sharp. By making use of a side-gate perpendicular to the two dimensional electron system, it is shown that the plateau widths can be changed or even eliminated altogether. Hence, the visibility of IQHE is strongly influenced when adjusting the edge potential profile and/or changing the dc current direction under high currents in the non-linear transport regime. As a second investigation, we consider two different types of ohmic contacts, namely highly transmitting (ideal) and highly reflecting (non-ideal) contacts. We show that if the injection contacts are non-ideal, however still ohmic, it is possible to measure directly the non-quantized transport taking place at the bulk of the CEO samples. The results of the experiments we propose will clarify the influence of the edge potential profile and the quality of the contacts, under quantized Hall conditions.Comment: Substantially revised version of manuscript arXiv:0906.3796v1, including new figures et

Impact of neoadjuvant therapy followed by laparoscopic radical gastrectomy with D2 lymph node dissection in Western population: A multi-institutional propensity score-matched study

Background and Objectives: In the setting of a minimally invasive approach, we aimed to compare short and long-term postoperative outcomes of patients treated with neoadjuvant therapy (NAT) + surgery or upfront surgery in Western population. Methods: All consecutive patients from six Italian and one Serbian center with locally advanced gastric cancer who had undergone laparoscopic gastrectomy with D2 lymph node dissection were selected between 2005 and 2019. After propensity score-matching, postoperative morbidity and oncologic outcomes were investigated. Results: After matching, 97 patients were allocated in each cohort with a mean age of 69.4 and 70.5 years. The two groups showed no difference in operative details except for a higher conversion rate in the NAT group (p = 0.038). The overall postoperative complications rate significantly differed between NAT + surgery (38.1%) and US (21.6%) group (p = 0.019). NAT was found to be related to a higher risk of postoperative morbidity in patients older than 60 years old (p = 0.013) but not in patients younger (p = 0.620). Conversely, no difference in overall survival (p = 0.41) and disease-free-survival (p = 0.34) was found between groups. Conclusions: NAT appears to be related to a higher postoperative complication rate and equivalent oncological outcomes when compared with surgery alone. However, poor short-term outcomes are more evident in patients over 60 years old receiving NAT