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Ground ice distribution and abundance have wide-ranging effects on periglacial environments and possible impacts on climate change scenarios. In contrast, very few studies measure ground ice in the High Arctic, especially in polar deserts and where coarse surficial material complicates coring operations. Ground ice volumes and cryostructures were determined for eight sites in a polar desert, near Resolute Bay, Nunavut, chosen for their hydrogeomorphic classification. Dry, unvegetated polar desert sites exhibited ice content close to soil porosity, with a

In formerly glaciated permafrost regions, extensive areas are still underlain by a considerable amount of glacier ice buried by glacigenic sediments. It is expected that large parts of glacier ice buried in the permafrost will melt in the near future, although the intensity and timing will depend on local terrain conditions and the magnitude and rate of future climate trends in different Arctic regions. The impact of these ice bodies on landscape evolution remains uncertain since the extent and volume of undisturbed relict glacier ice are unknown. These remnants of glacier ice buried and preserved in the permafrost contribute to the high spatial variability in ground ice condition of these landscapes, leading to the formation of lakes with diverse origins and morphometric and limnological properties. This study focuses on thermokarst lake initiation and development in response to varying ground ice conditions in a glacial valley on Bylot Island (Nunavut). We studied a lake-rich area using lake sediment cores, detailed bathymetric data, remotely sensed data and observations of buried glacier ice exposures. Our results suggest that initiation of thermokarst lakes in the valley was triggered from the melting of either buried glacier ice or intrasedimental ice and ice wedges. Over time, all lakes enlarged through thermal and mechanical shoreline erosion, as well as vertically through thaw consolidation and subsidence. Some of them coalesced with neighbouring water bodies to develop larger lakes. These glacial thermokarst lakes formed in buried glacier ice now evolve as “classic” thermokarst lakes that expand in area and volume as a result of the melting of intrasedimental ground ice in the surrounding material and the underlying glaciofluvial and till material. It is expected that the deepening of thaw bulbs (taliks) and the enlargement of Arctic lakes in response to global warming will reach undisturbed buried glacier ice where it is still present, which in turn will substantially alter lake bathymetry, geochemistry and greenhouse gas emissions from Arctic lowlands.

Arctic permafrost is degrading and is thus releasing nutrients, solutes, sediment and water into soils and freshwater ecosystems. The impacts of this degradation depends on the geochemical characteristics and in large part on the spatial distribution of ground ice and solutes, which is not well-known in the High Arctic polar desert ecosystems. This research links ground ice and solute concentrations, to establish a framework for identifying locations vulnerable to permafrost degradation. It builds on landscape classifications and cryostratigraphic interpretations of permafrost history. Well-vegetated wetland sites with syngenetic permafrost aggradation show a different geochemical signature from polar desert and epigenetic sites. In wetlands, where ground ice contents were high (+ and Cl− ions, reflecting a post-glacial marine inundation during permafrost formation. Dissolved organic carbon and total dissolved nitrogen concentrations usually increased at the top of permafrost and could not be as clearly associated with permafrost history. The research shows that the geochemistry of polar desert permafrost is highly dependent on permafrost history, and it can be estimated using hydrogeomorphological terrain classifications. The lower ice content of polar desert sites indicates that these areas are more vulnerable to thaw relative to the ice-rich wetland sites, and the elevated solute concentrations indicate that these areas could mobilise substantial solutes to downstream environments, should they become hydrologically connected with future warming.

A retrospective analysis was performed of preclinical and clinical data acquired during the evaluation of the estrogen receptor (ER) PET tracer 4-fluoro-11β-methoxy-16α-[18F]-fluoroestradiol (4FMFES) and its comparison with 16α-[18F]-fluoroestradiol (FES) in mice, rats, and humans with a focus on the brain uptake. Breast cancer tumor-bearing female BALB/c mice from a previous study and female Sprague-Dawley rats (control and ovariectomized) were imaged by 4FMFES or FES-PET imaging. Immediately after, low-dose CT was performed in the same bed position. Semi-quantitative analysis was conducted to extract %ID/g data. Small cohorts of mice and rats were imaged with 4FMFES in an ultra-high-resolution small animal PET scanner prototype (LabPET II). Rat brains were dissected and imaged separately with both PET and autoradiography. In parallel, 31 breast cancer patients were enrolled in a clinical phase II study to compare 4FMFES with FES for oncological assessment. Since the head was included in the field of view, brain uptake of discernable foci was measured and reported as SUVMax. Regardless of the species studied, 4FMFES and FES uptake were relatively uniform in most regions of the brain, except for bilateral foci at the base of the skull, at the midsection of the brain. Anatomical localization of the PET signal using CT image fusion indicates that the signal origins from the pituitary in all studied species. 4FMFES yielded lower pituitary uptake than FES in patients, but an inverse trend was observed in rodents. 4FMFES pituitary contrast was higher than FES in all assessed groups. High-resolution small animal imaging of the brain of rats and mice revealed a supplemental signal anterior to the pituitary, which is likely to be the medial preoptic area. Dissection data further confirmed those findings and revealed additional signals corresponding to the arcuate and ventromedial nuclei, along with the medial and cortical amygdala. 4FMFES allowed visualization of ER expression in the pituitary in humans and two different rodent species with better contrast than FES. Improvement in clinical spatial resolution might allow visualization and analysis of other ER-rich brain areas in humans. Further work is now possible to link 4FMFES pituitary uptake to cognitive functions.

Haptic technologies are widely used in multimedia entertainment to psychophysiologically enhance user experience. Psychometric-based research regarding vibrokinetic stimulation during multimedia viewing supports this notion. However, scant neurophysiological evidence exists to verify this effect. Using a between groups design with source-localized electroencephalography, the present study analyzed the effect of high fidelity vibrokinetic (HFVK) stimulation during passive multimedia interaction (i.e. watching a haptically enhanced movie) on self-reported emotional state and intercortical theta coherence. Results indicate that HFVK increases emotional reactivity in association with increased interhemispheric coherence between the right inferiortemporal gyrus and the left insular cortex, thereby conferring neurophysiological support for the efficaciousness of HFVK to enhance emotional response during movie watching.

PURPOSE: A retrospective analysis was performed of preclinical and clinical data acquired during the evaluation of the estrogen receptor (ER) PET tracer 4-fluoro-11β-methoxy-16α-[(18)F]-fluoroestradiol (4FMFES) and its comparison with 16α-[(18)F]-fluoroestradiol (FES) in mice, rats and humans with a focus on the brain uptake. PROCEDURES: Breast cancer tumor-bearing female BALB/c mice from a previous study and female Sprague-Dawley rats (control and ovariectomized) were imaged by 4FMFES or FES-PET imaging. Immediately after, low-dose CT was performed in the same bed position. Semi-quantitative analysis was conducted to extract %ID/g data. Small cohorts of mice and rats were imaged with 4FMFES in an ultra-high-resolution small animal PET scanner prototype (LabPET II). Rat brains were dissected and imaged separately with both PET and autoradiography. In parallel, 31 breast cancer patients were enrolled in a clinical phase II study to compare 4FMFES with FES for oncological assessment. Since the head was included in the field-of-view, brain uptake of discernable foci was measured and reported as SUV(Max). RESULTS: Regardless of the species studied, 4FMFES and FES uptake was relatively uniform in most regions of the brain, except for bilateral foci at the base of the skull, at the midsection of the brain. Anatomical localization of the PET signal using CT image fusion indicates that the signal origins from the pituitary in all studied species. 4FMFES yielded lower pituitary uptake than FES in patients, but an inverse trend was observed in rodents. 4FMFES pituitary contrast was higher than FES in all assessed groups. High-resolution small animal imaging of the brain of rats and mice revealed a supplemental signal anterior to the pituitary, which is likely to be the medial preoptic area. Dissection data further confirmed those findings and revealed additional signals corresponding to the arcuate and ventromedial nuclei, along with the medial and cortical amygdala. CONCLUSION: 4FMFES allowed visualization of ER expression in the pituitary in humans and two different rodent species with better contrast than FES. Improvement in clinical spatial resolution might allow visualization and analysis of other ER-rich brain areas in humans. Further work is now possible to link 4FMFES pituitary uptake to cognitive functions.

International audience; An increased interest in Arctic environments, mainly due to climate change, has changed the conditions for permafrost research in recent years. This change has been accompanied by a global increase in scientific publications, as well as a trend towards open access publications. We have analyzed abstracts, titles and keywords for publications on permafrost from 1998 to 2017 to identify developments (topics, impact and collaboration) in the field of permafrost research in light of these changes. Furthermore, to understand how scientists build on and are inspired by each other's work, we have (a) developed citation networks from scientific publications on permafrost and (b) conducted an online survey on inspiration in permafrost science. Our results show an almost 400% increase in publications containing the word permafrost in the title, keywords or abstract over the study period, and a strong increase in climate-change-related research in terms of publications and citations. Survey respondents (n = 122) find inspiration not only in scientific journal publications, but to a large extent in books and public outreach materials. We argue that this increase in global-scope issues (i.e., climate change) complementing core permafrost research has provided new incentives for international collaborations and wider communication efforts.

Introduction Gastrin releasing peptide receptors (GRPRs) are significantly over-expressed on a large proportion of prostate cancers making them prime candidates for receptor-mediated nuclear imaging by PET. Recently, we synthesized a novel bifunctional chelator (BFC) bearing hydroxamic acid arms (DOTHA 2 ). Here we investigated the potential of a novel DOTHA 2 -conjugated, 64 Cu-radiolabeled GRPR peptide antagonist, [D-Phe 6 -Sta 13 -Leu 14 -NH 2 ]bombesin(6-14) (DOTHA 2 -PEG-RM26) to visualize prostate tumors by PET imaging. Methods DOTHA 2 -PEG-RM26 was conveniently and efficiently assembled on solid support. The compound was radiolabeled with 64 Cu and its affinity, stability, cellular uptake on PC3 prostate cancer cells were evaluated. The in vitro and in vivo behavior of [ 64 Cu]DOTHA 2 -PEG-RM26 was examined by PET imaging using human PC3 prostate cancer xenografts and its behavior was compared to that of the analogous [ 64 Cu]NOTA-PEG-RM26. Results The inhibition constant of nat Cu-DOTHA 2 -PEG-RM26 was in the low nanomolar range (0.68 ± 0.19 nM). The [ 64 Cu]DOTHA 2 -PEG-RM26 conjugate was prepared with a labeling yield > 95% and molar activity of 56 ± 3 GBq/μmol after a 5-min room temperature labeling. [ 64 Cu]-DOTHA 2 -PEG-RM26 demonstrated rapid blood and renal clearance as well as a high tumor uptake. Small animal PET images confirmed high and specific uptake in PC3 tumor. Both [ 64 Cu]-DOTHA 2 -PEG-RM26 and [ 64 Cu]-NOTA-PEG-RM26 displayed similar tumor and normal tissue uptakes at early time point post injection. Conclusions [ 64 Cu]-DOTHA 2 -PEG-RM26 allows visualization of prostate tumors by PET imaging. DOTHA 2 enables fast 64 Cu chelation under mild condition, and as such could be used advantageously for the development of other 64 Cu-labeled peptide-derived PET tracers.

In this study, the preliminary results of a phase II clinical trial investigating the use of the Estrogen Receptor (ER) targeting PET tracer 4-fluoro-11β-methoxy-16α-[18F]fluoroestradiol (18F-4FMFES) and [18F]-fluorodeoxyglucose (18F-FDG)-PET in endometrial cancers will be accounted. In parallel, non-invasive interventions will be attempted to slow down progression of 18F-4FMFES metabolites in the intestines to reduce abdominal background. Methods: In an ongoing study, 25 patients that received prior pathological confirmation of an ER+ endometrial cancer or endometrial intraepithelial neoplasia agreed to participate to the ongoing clinical trial. Patients were scheduled for 18F-FDG and 18F-4FMFES PET/CT imaging in random order and within 2 weeks. Patients were administered either 4 mg loperamide per os before 18F-4FMFES tracer injection or repeated intravenous injection of 20 mg hyoscine N-butylbromide during 18F-4FMFES-PET/CT. Regions-of-interest (ROIs) covering the whole abdomen and excluding the liver, bladder and uterus were drawn for the 18F-4FMFES-PET images, and a threshold of SUV > 4 was applied. The volume of the resulting region was compared between the different interventions to estimate the extent of the intestinal background. Results: Repeated injection of hyoscine N-butylbromide substantially reduced the intestinal background volume, whereas loperamide had a significant but moderate effect. 18F-4FMFES tumor uptake ranged between SUVmax 3.0 and 14.4 (9.4 ± 3.2), whereas 18F-FDG uptake spreaded between SUVmax 0 and 22.0 (7.5 ± 5.1). Tumor-to-background ratio were significantly higher for 18F-4FMFES (16.4 ± 5.4) than for 18F-FDG (7.4 ± 4.6). Significant differences were observed between grade 1 and higher-grade tumors concerning 18F-4FMFES uptake and contrast. 18F-FDG uptake, and the 18F-FDG/18F-4FMFES uptake ratio. Conclusion: It is possible to improve 18F-4FMFES abdominal background using hyoscine N-butylbromide. Both 18F-FDG and 18F-4FMFES-PET are suitable for detection of ER+ endometrial cancers, although 18F-4FMFES yielded a better tumor contrast than 18F-FDG.

After encouraging preclinical and human dosimetry results for the novel estrogen receptor (ER) PET radiotracer 4-fluoro-11β-methoxy-16α-18F-fluoroestradiol (18F-4FMFES), a phase II clinical trial was initiated to compare the PET imaging diagnostic potential of 18F-4FMFES with that of 16α-18F-fluoroestradiol (18F-FES) in ER-positive (ER+) breast cancer patients. Methods: Patients diagnosed with ER+ breast cancer (n = 31) were recruited for this study, including 6 who underwent mastectomy or axillary node dissection. For each patient, 18F-FES and 18F-4FMFES PET/CT scans were done sequentially (within a week) and in random order. One hour after injection of either radiotracer, a head-to-thigh static scan with a 2-min acquisition per bed position was obtained. Blood samples were taken at different times after injection to assess each tracer metabolism by reverse-phase thin-layer chromatography. The SUVmean of nonspecific tissues and the SUVmax of the tumor were evaluated for each detected lesion, and tumor-to-nonspecific organ ratios were calculated. Results: Blood metabolite analysis 60 min after injection of the tracer showed a 2.5-fold increase in metabolic stability of 18F-4FMFES over 18F-FES. Although for most foci 18F-4FMFES PET had an SUVmax similar to that of 18F-FES PET, tumor contrast improved substantially in all cases. Lower uptake was consistently observed in nonspecific tissues for 18F-4FMFES, notably a 4-fold decrease in blood-pool activity as compared with 18F-FES. Consequently, image quality was considerably improved using 18F-4FMFES, with lower overall background activity. As a result, 18F-4FMFES successfully identified 9 more lesions than 18F-FES. Conclusion: This phase II study with ER+ breast cancer patients showed that 18F-4FMFES PET achieves a lower nonspecific signal and better tumor contrast than 18F-FES PET, resulting in improved diagnostic confidence and lower false-negative diagnoses.

Repeated freeze–thaw cycles on slopes trigger sorting and solifluction mass movements, while subsequent displacement of material modifies the geomorphology of slopes as well as permafrost dynamics. This study focuses on the geomorphology and the cryostratigraphy of a polar desert stone-banked solifluction lobe with the objective to clarify the impact of slow mass movements on ground ice aggradation. The morphology of the solifluction lobe was characterized by peripheral ridges of coarse gravel, partially surrounding a depression filled with finer sediments saturated with water and covered by organics. Cryostratigraphic analysis demonstrated that the solifluction lobe’s formation led to the development of a syngenetic layer of permafrost with an ice content that varied according to the location in the lobe. The ice-rich cryofacies formed in the central depression of the lobe should act as a buffer to potential active layer deepening, slowing down its thawing, whereas the ice-poor cryofacies formed under the ridges is expected to thaw faster than the central depression under climate warming scenarios. Thawing of the ice-rich zone in the future will result in differential thaw subsidence between the ridges and the central depression of solifluction lobes, along with increased drainage through the ridges and subsequent changes in hydrology.

Water tracks play a major role in the headwater basin hydrology of permafrost landscapes in Alaska and Antarctica, but less is known about these features in the High Arctic. We examined the physical and hydrological properties of water tracks on Ward Hunt Island, a polar desert site in the Canadian High Arctic, to evaluate their formation process and to compare with water tracks reported elsewhere. These High Arctic water tracks flowed through soils that possessed higher near-surface organic carbon concentrations, higher water content, and coarser material than the surrounding soils. The water track morphology suggested they were initiated by a combination of sorting, differential frost heaving, and eluviation. The resultant network of soil conduits, comparable to soil pipes, dominated the hydrology of the slope. The flow of cold water through these conduits slowed down the progression of the thawing front during summer, making the active layer consistently shallower relative to adjacent soils. Water tracks on Ward Hunt Island, and in polar desert catchments with these features elsewhere in the High Arctic, strongly influence slope hydrology and active-layer properties while also affecting vegetation distribution and the quality of runoff to the downstream lake.

In this study, we investigated for the first time the influence of 2-aminoethyl-piperazine-1-carboxylic acid (APCA) and amino-hexanedioic-1-acid (AHDA) on tumor uptake and elimination kinetics of [64Cu]-radiolabeled gastrin releasing peptide receptors (GRPR) antagonists. Three GRPR antagonists containing the RM26 sequence were synthesized and conjugated with NOTA via different linkers (LK): polyethylene glycol (PEG–neutral), APCA (dicationic) or AHDA (dianionic). The NOTA-LK-RM26 peptides were radiolabeled with 64Cu to assess their pharmacokinetic and positron emission tomography (PET) imaging properties using PC3 tumor-bearing athymic nude mice. The inhibition constants (Ki) of the 3 natCu/NOTA-LK-RM26 peptides bearing PEG, dicationic and dianionic linkers were 0.98 ± 0.48 nM, 0.95 ± 0.21 nM, and 17.97 ± 2.79 nM, respectively. The [64Cu] NOTA-LK-RM26 conjugates were prepared with labeling yields superior to 95% and specific activities of 67 to 77 TBq/mmol. The 3 radiopeptides were stable in vivo and showed GRPR-specific uptake in pancreas with a very fast washout of this tissue observed for [64Cu]-NOTA-AHDA-RM26 peptide. Results from imaging studies displayed specific PC3 tumor uptake for both [64Cu]-NOTA-APCA- and AHDA-RM26, similar kidney elimination and fast liver washout. Considering their adequate imaging characteristics, [64Cu]-NOTA-LK-RM26 bearing APCA- and AHDA-linkers are promising candidates for GRPR-targeted PET imaging prostate cancer.

In vivo imaging of estrogen receptor (ER) densities in human breast cancer is a potential tool to stage disease, guide treatment protocols and follow-up on treatment outcome. Both positron emission tomography (PET) and fluorescence imaging have received ample attention to detect ligand-ER interaction. In this study we prepared BODIPY-estradiol conjugates using 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) as fluorescent probe and estradiol derivatives as ligand and established their relative binding affinity (RBA) for the ERα. The synthesis of the conjugates involves attachment of a BODIPY moiety to the C17α-position of estradiol using Sonogashira or click reactions of iodo-BODIPY or aza-BODIPY with various 17α-ethynylestradiol (EE2) derivatives. The highest RBA for the ERα was observed with the EE2-BODIPY conjugate (7) featuring a linear eight carbon spacer chain. Cell uptake studies and in vivo imaging experiments in an ER-positive mouse tumor model are in progress.

Thermokarst lakes are widespread and diverse across permafrost regions and they are considered significant contributors to global greenhouse gas emissions. Paleoenvironmental reconstructions documenting the inception and development of these ecologically important water bodies are generally limited to Pleistocene-age permafrost deposits (Yedoma) of Siberia, Alaska, and the western Canadian Arctic. Here we present the gradual transition from syngenetic ice-wedge polygon terrains to a thermokarst lake in the Eastern Canadian Arctic. We combine geomorphological surveys with paleolimnological reconstructions from sediment cores in an effort to characterize local landscape evolution from terrestrial to freshwater environment. Located on an ice-rich and organic-rich polygonal terrace, the studied lake is now evolving through active thermokarst, as revealed by subsiding and eroding shores, and was likely created by water pooling within a pre-existing topographic depression. Organic sedimentation in the valley started during the mid-Holocene, as documented by the oldest organic debris found at the base of one sediment core and dated at 4.8 kyr BP. Local sedimentation dynamics were initially controlled by fluctuations in wind activity, local moisture and vegetation growth/accumulation, as shown by alternating loess (silt) and peat layers. Fossil diatom assemblages were likewise influenced by local hydro-climatic conditions and reflect a broad range of substrates available in the past (both terrestrial and aquatic). Such conditions likely prevailed until ~ 2000 BP, when peat accumulation stopped as water ponded the surface of degrading ice-wedge polygons, and the basin progressively developed into a thermokarst lake. Interestingly, this happened in the middle of the Neoglacial cooling period, likely under wetter-than-average conditions. Thereafter, the lake continued to develop as evidenced by the dominance of aquatic (both benthic and planktonic) diatom taxa in organic-rich lacustrine muds. Based on these interpretations, we present a four-stage conceptual model of thermokarst lake development during the late Holocene, including some potential future trajectories. Such a model could be applied to other formerly glaciated syngenetic permafrost landscapes.

In the last decade, entertainment industries have been creating multi-sensory experiences using haptic stimulation delivered via vibro-kinetic (VK) seats that produce vibration and motion coincidental with audiovisual content. However, the effects of VK stimulation during purely auditory experiences remains unclarified. We addressed this scientific shortcoming by investigating the effects of high fidelity VK (HFVK) stimulation, on psychophysiological indices of emotional valence and arousal. The HFVK stimulation was delivered to 24 healthy participants through an HFVK enhanced seat during active music listening. Participants listened to six popular songs randomly chosen from a pool of 15 songs, with the songs presented randomly with or without HFVK stimulation. Psychological emotional valence and arousal were indexed based on two items of the Self-Assessment Manikin (SAM) scale. Physiological emotional valence and arousal were respectively indexed based on micro facial expressions and electrodermal activity. Our results revealed that psychological and physiological valence, and psychological arousal were higher with HFVK stimulation compared to a control condition where the chair was static. A post-experiment questionnaire further revealed greater subjective appreciation for the HFVK stimulation condition compared to the control condition. Overall, our results highlight the potential for HFVK technologies to enhance auditory listening experiences.

Investigations into the susceptibility of permafrost landscapes response to thermokarst can be performed using various approaches, depending on the scale of investigation. In many cases, point-based field measurements are extrapolated to larger scales and vice versa. The integration of scales often requires some form of ground control in addition to remote sensing surveys, which are at times exclusively conducted. As upscaling from discrete field measurements can provide spatial coverage and landscape-scale significance, downscaling from remote sensing can offer insight into processes and serve as calibration or verification. Here we present a multiple-scale evaluation of an area initially interpreted as a relict active layer detachment slide (before 1950) on Melville Island in the High Arctic, where differential interferometric synthetic aperture radar (DInSAR) showed subsidence between 2013 and 2015. Ground-based, cryostratigraphy measurements were combined with ground-penetrating radar (GPR) to investigate permafrost ice-content. The results indicate greater subsidence within the relict active layer detachment as detected by DInSAR. GPR surveys and permafrost coring indicated the presence of an ice-rich or massive ice layer near the base of the active layer in this area. In addition, cryostratigraphic evidences of thaw unconformity and of massive ice depth helped validate the interpretations of the geomorphology in the active layer detachment. This combination of methods indicated a localized and inherited landform-subsidence association, which brought further insight into the interpretation of DInSAR subsidence data. The framework presented in this study demonstrates the importance of site-specific investigations of thermokarst signal in order to understand the processes behind the remote sensing results.

Permafrost occupies 20 million square kilometres of Earth's high-latitude and high-altitudelandscapes. These regions are sensitive to climate change and human activities; hence,permafrost research is of considerable scientific and societal importance. However, the resultsof this research are generally not known by the general public. Communicating scientificconcepts is an increasingly important task in the research world. Different ways to engagelearners and incorporate narratives in teaching materials exist, yet they are generallyunderused. Here we report on an international scientific outreach project called “FrozenGround Cartoons”, which aims at making permafrost science accessible and fun for students,teachers, and parents through the creation of comic strips. We present the context in whichthe project was initiated, and recent education and outreach activities. The future phases ofthe project primarily involve a series of augmented reality materials, such as maps, photos,videos, and 3D drawings. With this project we aim to foster understanding of permafrostresearch among broader audiences, inspire future permafrost researchers, and raise publicand science community awareness of polar science, education, outreach, and engagement.

Field records, aerial photographs, and satellite imagery show that the perennial ice cover on Ward Hunt Lake at Canada's northern coast experienced rapid contraction and thinning after at least 50 years of relative stability. On all dates of sampling from 1953 to 2007, 3.5 to 4.3 m of perennial ice covered 65–85% of the lake surface in summer. The ice cover thinned from 2008 onward, and the lake became ice free in 2011, an event followed by 26 days of open water conditions in 2012. This rapid ice loss corresponded to a significant increase in melting degree days (MDD), from a mean (±SD) of 80.4 (±36.5) MDD (1996–2007) to 136.2 (±16.4) MDD (2008–2012). The shallow bathymetry combined with heat advection by warm inflows caused feedback effects that accelerated the ice decay. These observations show how changes across a critical threshold can result in the rapid disappearance of thick perennial ice.

After encouraging preclinical and human dosimetry results for the novel estrogen receptor (ER) PET radiotracer 4-fluoro-11β-methoxy-16α-(18)F-fluoroestradiol ((18)F-4FMFES), a phase II clinical trial was initiated to compare the PET imaging diagnostic potential of (18)F-4FMFES with that of 16α-(18)F-fluoroestradiol ((18)F-FES) in ER-positive (ER+) breast cancer patients. Methods: Patients diagnosed with ER+ breast cancer (n = 31) were recruited for this study, including 6 who underwent mastectomy or axillary node dissection. For each patient, (18)F-FES and (18)F-4FMFES PET/CT scans were done sequentially (within a week) and in random order. One hour after injection of either radiotracer, a head-to-thigh static scan with a 2-min acquisition per bed position was obtained. Blood samples were taken at different times after injection to assess each tracer metabolism by reverse-phase thin-layer chromatography. The SUV(mean) of nonspecific tissues and the SUV(max) of the tumor were evaluated for each detected lesion, and tumor-to-nonspecific organ ratios were calculated. Results: Blood metabolite analysis 60 min after injection of the tracer showed a 2.5-fold increase in metabolic stability of (18)F-4FMFES over (18)F-FES. Although for most foci (18)F-4FMFES PET had an SUV(max) similar to that of (18)F-FES PET, tumor contrast improved substantially in all cases. Lower uptake was consistently observed in nonspecific tissues for (18)F-4FMFES, notably a 4-fold decrease in blood-pool activity as compared with (18)F-FES. Consequently, image quality was considerably improved using (18)F-4FMFES, with lower overall background activity. As a result, (18)F-4FMFES successfully identified 9 more lesions than (18)F-FES. Conclusion: This phase II study with ER+ breast cancer patients showed that (18)F-4FMFES PET achieves a lower nonspecific signal and better tumor contrast than (18)F-FES PET, resulting in improved diagnostic confidence and lower false-negative diagnoses.

Gastrin releasing peptide receptors (GRPRs) are significantly over-expressed on a large proportion of prostate cancers making them prime candidates for receptor-mediated nuclear imaging by PET. Recently, we synthesized a novel bifunctional chelator (BFC) bearing hydroxamic acid arms (DOTHADOTHAThe inhibition constant of[

Purpose Trimebutine 3-thiocarbamoylbenzenesulfonate (GIC-1001) is a new drug intended to be used for the management of visceral pain in patients undergoing sedation-free, full colonoscopy. The objectives of this Phase I, single-center, randomized, double-blinded, placebo-controlled, integrated study were to evaluate the safety and pharmacokinetics of GIC-1001 after single ascending doses (SAD) and multiple ascending doses (MAD) and to evaluate the influence of food on the pharmacokinetics in healthy volunteers. Methods GIC-1001 or placebo was orally administered to 80 healthy male and female subjects (non- or ex-smokers) aged 18 to 50 years with a body mass index between 18.5 and 30 kg/m 2 . The SAD portion of the study consisted of 5 cohorts with dose levels of 125 to 1000 mg. The MAD portion included 4 cohorts in which subjects received TID doses of 125 to 500 mg over 7 days (19 consecutive doses). Subjects were randomized (6:2) to receive GIC-1001 or placebo. The third portion of the study included a single 375-mg dose of GIC-1001 in a randomized, 2-period, crossover design to assess the influence of food (n = 8 subjects). Safety was evaluated by using adverse events (AEs), vital signs, ECGs, physical examination, cardiac monitoring, and laboratory test results. The analytes were assayed by using validated HPLC-MS/MS methods. Pharmacokinetic parameters were evaluated by using a noncompartmental analysis, and regression models were used to assess dose linearity. To evaluate the effect of food, 90% CIs of the ratio of geometric least squares means from ln-transformed pharmacokinetic parameters were calculated. Findings The most frequently reported drug-related AEs were of nervous system and gastrointestinal origin. The most common AEs included headache, somnolence, and nausea. After single-dose administration, T max of trimebutine ranged from 1.0 to 1.5 hours. C max and AUC T were linear (nonlinearity P ≥ 0.05) and proportional ( P max and AUC of trimebutine; the ratio of geometric least squares means (90% CI) were 140% (84–234) and 174% (138–221), respectively. In the MAD study portion, the T max of trimebutine ranged from 0.5 to 2 hours and AUC τ increased from 38 to 170 ng · h/mL. AUC τ and C max were linear and proportional over the studied dose range. Implications GIC-1001 was well tolerated, and its safety profile was similar to that of placebo. Pharmacokinetics of GIC-1001 and its metabolites were mainly linear and proportional over the studied dose ranges. Steady state was generally considered to be reached after 3 days. Food consumption affected the pharmacokinetic profile of the analytes differently. (ClinicalTrials.gov identifier: NCT01738425.)

218 Objectives: Several studies have shown that liver tumor burden (LTB), estimated by morphological modalities, such as CT and MR, is a significant factor for management and prognosis in patients with neuroendocrine tumors (NETs). PET/CT using 68Ga-DOTATOC or 18F-FDG, as a functional imaging tool, has been widely used in NETs, which might provide additional information for predicting prognosis. The aim of this study was to investigate the prognostic performance of DOTATOC-PET/CT and FDG-PET/CT in comparison to the morphological imaging modalities. Methods: We retrospectively analyzed 31 patients (male:female=17:14, 22-84 y.o.) with pancreatic NETs who had undergone DOTATOC-PET/CT and had been diagnosed to have liver metastasis by some imaging modalities. All patients had enhanced CT and/or MRI within a month of DOTATOC-PET/CT, and 26 patients FDG-PET/CT. We assessed LTB by a visual scale (0-10%, 10-25%, 25-50%, 50%-) on CT or MRI images. Then, we measured maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion uptake (TLU) on DOTATOC-PET/CT or total lesion glycolysis (TLG) on FDG-PET/CT for all metastatic liver tumors or all lesions in a whole body. In addition, the SUVmax ratio, MTV ratio, and TLU ratio, defined as a value in FDG-PET/CT divided by a value in DOTATOC-PET/CT, were calculated. The progression-free survival (PFS) and the overall survival (OS) were evaluated during their follow-up periods (8-83mo). The Kaplan-Meier analysis with the log-rank test was used to estimate and compare the correlation between each imaging parameter and PFS or OS. Results: On CT and/or MRI (n=31), LTB was significantly negatively correlated with PFS (p=0.003) and OS (p=0.007) [Fig. 1, 2]. On DOTATOC-PET/CT (n=31), 27 patients had DOTATOC-avid liver metastases and 30 patients had DOTATOC-avid lesions. The absence of DOTATOC-avid lesions was significantly negatively correlated with OS (p=0.041), although the number of the non-avid group was only one. Among the DOTATOC-PET/CT parameters, SUVmax, MTV, TLU for liver metastases and MTV for all lesions were significantly negatively correlated with PFS (p=0.003, p=0.005, p=0.006, p

The aim of this study was to compare the in vivo stability, uptake, and positron emission tomography (PET) imaging performance of a novel estrogen receptor PET tracer, 4-fluoro-11β-methoxy-16α-[(18)F]fluoroestradiol (4FMFES), with 16α-[(18)F]fluoroestradiol (FES).MC7-L1 and MC4-L2 (ER+) cell lines and their ERα-knockdown variants (ERαKD) were implanted subcutaneously in Balb/c mice. After 21 days, mice were imaged using either FES or 4FMFES. One hour post-injection, static images were acquired for 30 min and the tumor %ID/g uptake values were derived. Biodistribution data were also obtained 1 h following the injection of either FES or 4FMFES. Blood samples were taken at different times and analyzed on thin-layer chromatography to quantify the presence of radiometabolites for each radiotracer. To assess specific targeting to the estrogen receptors, mice bearing only ER+ tumors were treated with the competitive ER inhibitor fulvestrant 48 h prior to imaging with 4FMFES.Metabolic stability was found to be similar for both tracers in mice. Both FES and 4FMFES differentiated ER+ tumors from ERαKD tumors in biodistribution and PET imaging studies. 4FMFES achieved a significantly higher %ID/g uptake in ER+ tumors and MC4-L2 ERαKD tumors than FES in the PET imaging studies. Also, tumor-to-background ratio was higher in ER+ tumors using 4FMFES compared to FES. Dissection data showed a significantly higher %ID/g in all tested cell lines and ER-rich tissues using 4FMFES versus FES. Fulvestrant-treated mice had either low or undetectable tumor uptake.In a tumor-bearing mouse model, 4FMFES achieves better specific tumor uptake and better contrast than FES, making it a promising candidate for ER imaging.

In this study, we investigated for the first time the influence of 2-aminoethyl-piperazine-1-carboxylic acid (APCA) and amino-hexanedioic-1-acid (AHDA) on tumor uptake and elimination kinetics of [

OP03 Selective extraction of medically-related radionuclides from proton-irradiated thorium targets, V. Radchenko, J.W. Engle, C. Roy, J. Griswold, M.F. Nortier, E.R. Birnbaum, M. Brugh, S. Mirzadeh, K. D. John, M.E. Fassbender, OP04 Comparison of [68Ga]FSC(succ-RGD)3 and [68Ga]NODAGA-RGD for PET imaging of αvβ3 integrin expression, Chuangyan Zhai, Gerben M. Franssen, Milos Petrik, Peter Laverman, Clemens Decristoforo, OP05 A new NPY-Y1R targeting peptide for breast cancer PET imaging, Ait-Mohand Samia, Dumulon-Perreault Véronique, Guérin Brigitte, OP06 The influence of multivalency on CCK 2 receptor targeting, D. Summer, A. Kroess, C. Rangger, H. Haas, P. Laverman, F. Gerben, E. von Guggenberg, C.Decristoforo, OP07 SPECT Imaging of αvβ3 Expression by [99mTc(N)PNP43]- Bifunctional Chimeric RGD Peptide not Cross-Reacting with αvβ5, Cristina Bolzati, Nicola Salvarese, Fiorenzo Refosco, Laura Meléndez-Alafort, Debora Carpanese, Antonio Rosato, Michele Saviano, Annarita Del Gatto, Daniela Comegna, Laura Zaccaro, OP09 New dienophiles for the inverse-electron-demand Diels-Alder reaction and for pretargeted PET imaging, Emilie Billaud, Muneer Ahamed, Frederik Cleeren, Elnaz Shahbazali, Tim Noël, Volker Hessel, Alfons Verbruggen and Guy Bormans, OP10 New complexing agent for Al18F-labelling of heat-sensitive biomolecules: Synthesis and preclinical evaluation of Al18F-RESCA1-HAS, Cleeren F, Lecina J, Koole M, Verbruggen A and Bormans G, OP11 A novel versatile precursor efficient for F-18 radiolabelling via click-chemistry, B. Lugatoa, S. Stucchia, E.A. Turollaa, L. Giulianoa, S.Toddea, P. Ferraboschib, OP12 A general applicable method to quantify unidentified UV impurities in radiopharmaceuticals, R.P. Klok, M.P.J. Mooijer, N.H. Hendrikse, A.D. Windhorst, OP13 Development of [18F]Fluoro-C-glycosides to radiolabel peptides, Collet C., Petry N., Chrétien F., Karcher G., Pellegrini-Moïse N., Lamandé-Langle S., OP14 A Microfluidic Approach for the 68Ga-labeling of PSMAHBED-CC and NODAGA-RGD, Sarah Pfaff, Cecile Philippe, Markus Mitterhauser, Marcus Hacker, Wolfgang Wadsak, OP16 Surprising reactivity of astatine in the nucleophilic substitution of aryliodonium salts: application to the radiolabeling of antibodies, François Guérard, Yong-Sok Lee, Sébastien Gouard, Kwamena Baidoo, Cyrille Alliot, Michel Chérel, Martin W. Brechbiel, Jean-François Gestin, OP17 64Cu-NOTA-pertuzumab F(ab')2 fragments, a second-generation probe for PET imaging of the response of HER2-positive breast cancer to trastuzumab (Herceptin), Lam K, Chan C, Reilly RM, OP18 Development of radiohalogenated analogues of a avb6-specific peptide for high LET particle emitter targeted radionuclide therapy of cancer, Salomé Paillas, John Marshall, Jean-Pierre Pouget, Jane Sosabowski, OP19 Ligand Specific Efficiency (LSE) as a guide in tracer optimization, Emmanuelle Briard, Yves P. Auberson, John Reilly, Mark Healy, David Sykes, OP23 The radiosynthesis of an 18F-labeled triglyceride, developed to visualize and quantify brown adipose tissue activity, Andreas Paulus, Wouter van Marken Lichtenbelt,Felix Mottaghy, Matthias Bauwens, OP24 Influence of the fluorescent dye on the tumor targeting properties of dual-labeled HBED-CC based PSMA inhibitors, Baranski, Ann-Christin, Schäfer, Martin, Bauder-Wüst, Ulrike, Haberkorn, Uwe, Eder, Matthias, Kopka, Klaus, OP25 [18F]MEL050 as a melanin PET tracer : fully automated radiosynthesis and evaluation for the detection of pigmented melanoma in mice pulmonary metastases, Chaussard M, Hosten B, Vignal N, Tsoupko-Sitnikov V, Hernio N, Hontonnou F, Merlet P, Poyet JL, Sarda-Mantel L, Rizzo-Padoin N, OP26 Design and Preclinical Evaluation of Novel Radiofluorinated PSMA Targeting Ligands Based on PSMA-617, J. Cardinale, M. Schäfer, M. Benešová, U. Bauder-Wüst, O. Seibert, F. Giesel, U. Haberkorn, M. Eder, K. Kopka, OP27 A novel radiolabeled peptide for PET imaging of prostate cancer: 64Cu-DOTHA2-PEG-RM26, Mansour Nematallah, Paquette Michel, Ait-Mohand Samia, Dumulon-Perreault Véronique, Lecomte Roger, Guérin Brigitte, OP29 Biodistribution of [18F]Amylovis®, a new radiotracer PET imaging of β-amyloid plaques, Fernandez-Maza L, Rivera-Marrero S, Prats Capote A, Parrado-Gallego A, Fernandez-Gomez I, Balcerzyk M, Sablon-Carrazana M, Perera-Pintado A, Merceron-Martinez D, Acosta-Medina E, Rodriguez-Tanty C, OP30 Synthesis and preclinical evaluation of [11C]-BA1 PET tracer for the imaging of CSF-1R, Bala Attili, Muneer Ahamed, Guy Bormans, OP31 In vivo imaging of the MCHR1 in the ventricular system via [18F]FE@SNAP, C. Philippe, M. Zeilinger, T. Scherer, C. Fürnsinn, M. Dumanic, W. Wadsak, M. Hacker, M. Mitterhauser, OP32 Synthesis of the first carbon-11 labelled P2Y12 receptor antagonist for imaging the anti-inflammatory phenotype of activated microglia, B. Janssen, D.J. Vugts, G.T. Molenaar, U. Funke, P.S. Kruijer, F. Dollé, G. Bormans, A.A. Lammertsma, A.D. Windhorst, OP33 Radiosynthesis of a selective HDAC6 inhibitor [11C]KB631 and in vitro and ex vivo evaluation, Koen Vermeulen, Muneer Ahamed, Michael Schnekenburger, Mathy Froeyen, Dag Erlend Olberg, Marc Diederich, Guy Bormansa, OP34 Improving metabolic stability of fluorine-18 labelled verapamil analogues, Raaphorst RM, Luurtsema G, Lammertsma AA, Elsinga PH, Windhorst AD, OP36 Development of a novel PET tracer for the activin receptor-like kinase 5, Lonneke Rotteveel, Uta Funke, Peter ten Dijke, Harm Jan Bogaard, Adriaan A. Lammertsma, Albert D. Windhorst, OP37 SPECT imaging and biodistribution studies of 111In-EGF-Au-PEG nanoparticles in vivo, Lei Song, Sarah Able, Nadia Falzone, Veerle Kersemans, Katherine Vallis, OP38 Melanoma targeting with [99mTc(N)(PNP3)]-labeled NAPamide derivatives: preliminary pharmacological studies, Davide Carta, Nicola Salvarese, Wiebke Sihver, Feng Gao, Hans Jürgen Pietzsch, Barbara Biondi, Paolo Ruzza, Fiorenzo Refosco, Cristina Bolzati, OP39 [68Ga]NODAGA-RGD: cGMP synthesis and data from a phase I clinical study, Roland Haubner, Armin Finkensted, Armin Stegmair, Christine Rangger, Clemens Decristoforo, Heinz Zoller, Irene J. Virgolin, OP44 Implementation of a GMP-grade radiopharmacy facility in Maastricht, Ivo Pooters, Maartje Lotz, Roel Wierts, Felix Mottaghy, Matthias Bauwens, OP45 Setting up a GMP production of a new radiopharmaceutical, Forsback, Sarita, Bergman Jörgen, Kivelä Riikka, OP48 In vitro and in vivo evaluation of 68-gallium labeled Fe3O4-DPD nanoparticles as potential PET/MRI imaging agents, M. Karageorgou, M. Radović, C. Tsoukalas, B. Antic, M. Gazouli, M. Paravatou-Petsotas, S. Xanthopouls, M. Calamiotou, D. Stamopoulos, S. Vranješ-Durić, P. Bouziotis, OP49 Fast PET imaging of inflammation using 68Ga-citrate with Fe-containing salts of hydroxy acids, A. S. Lunev, A. A. Larenkov, K.A. Petrosova, O. E. Klementyeva, G. E. Kodina, PP01 Installation and validation of 11C-methionine synthesis, Kvernenes, O.H., Adamsen, T.C.H., PP02 Fully automated synthesis of 68Ga-labelled peptides using the IBA Synthera® and Synthera® Extension modules, René Martin, Sebastian Weidlich, Anna-Maria Zerges, Cristiana Gameiro, Neva Lazarova, Marco Müllera, PP03 GMP compliant production of 15O-labeled water using IBA 18 MeV proton cyclotron, Gert Luurtsema, Michèl de Vries, Michel Ghyoot, Gina van der Woude, Rolf Zijlma, Rudi Dierckx, Hendrikus H. Boersma, Philip H. Elsinga, PP04 In vitro Nuclear Imaging Potential of New Subphthalocyanine and Zinc Phthalocyanine, Fatma Yurt Lambrecht, Ozge Er, Mine Ince, Cıgır Biray Avci, Cumhur Gunduz, Fatma Aslihan Sarı, PP05 Synthesis, Photodynamic Therapy Efficacy and Nuclear Imaging Potential of Zinc Phthalocyanines, Kasim Ocakoglu, Ozge Er, Onur Alp Ersoz, Fatma Yurt Lambrecht, Mine Ince, Cagla Kayabasi, Cumhur Gunduz, PP06 Radio-U(H)PLC – the Search on the Optimal Flow Cell for the γ-Detector, Torsten Kniess, Sebastian Meister, Steffen Fischer, Jörg Steinbach, PP07 Radiolabeling, characterization & biodistribution study of cysteine and its derivatives with Tc99m, Rabia Ashfaq, Saeed Iqbal, Atiq-ur-Rehman, Irfan ullah Khan, PP08 Radiolabelling of poly (lactic-co.glycolic acid) (PLGA) nanoparticles with 99mTC, R Iglesias-Jerez, Cayero-Otero, L. Martín-Banderas, A. Perera-Pintado, I. Borrego-Dorado, PP09 Development of [18F]PD-410 as a non-peptidic PET radiotracer for gastrin releasing peptide receptors, Ines Farinha-Antunes, Chantal Kwizera, Enza Lacivita, Ermelinda Lucente, Mauro Niso, Paola De Giorgio, Roberto Perrone, Nicola A. Colabufo, Philip H. Elsinga, Marcello Leopoldo, PP10 An improved nucleophilic synthesis of 2-(3,4-dimethoxyphenyl)-6-(2-[18F]fluoroethoxy) benzothiazole ([18F]FEDMBT), potential diagnostic agent for breast cancer imaging by PET, V.V. Vaulina, O.S. Fedorova, V.V. Orlovskaja, ?�.L. Chen, G.Y. Li, F.C. Meng, R.S. Liu, H.E. Wang, R.N. Krasikova, PP11 Internal radiation dose assessment of radiopharmaceuticals prepared with accelerator-produced 99mTc, Laura Meléndez-Alafort, Mohamed Abozeid, Guillermina Ferro-Flores, Anna Negri, Michele Bello, Nikolay Uzunov, Martha Paiusco, Juan Esposito, Antonio Rosato, PP12 A specialized five-compartmental model software for pharmacokinetic parameters calculation, Laura Meléndez-Alafort, Cristina Bolzati, Guillermina Ferro-Flores, Nicola Salvarese, Debora Carpanese, Mohamed Abozeid, Antonio Rosato, Nikolay Uzunov, PP13 Molecular imaging of the pharmacokinetic behavior of low molecular weight 18F-labeled PEtOx in comparison to 89Zr-labeled PEtOx, Palmieri L, Verbrugghen T, Glassner M, Hoogenboom R, Staelens S, Wyffels L, PP14 Towards nucleophilic synthesis of the α-[18F]fluoropropyl-L-dihydroxyphenylalanine, V. V. Orlovskaja, O. F. Kuznetsova, O. S. Fedorova, V. I. Maleev, Yu. N. Belokon, A. Geolchanyan, A. S. Saghyan, L. Mu, R. Schibli, S. M. Ametamey, R. N. Krasikova, PP15 A convenient one-pot synthesis of [18F]clofarabine, Revunov, Evgeny, Malmquist, Jonas, Johnström, Peter, Van Valkenburgh, Juno, Steele, Dalton, Halldin, Christer, Schou, Magnus, PP16 BODIPY-estradiol conjugates as multi-modality tumor imaging agents, Samira Osati,Michel Paquette,Simon Beaudoin,Hasrat Ali,Brigitte Guerin, Jeffrey V. Leyton, Johan E. van Lier, PP17 Easy and high yielding synthesis of 68Ga-labelled HBED-PSMA and DOTA-PSMA by using a Modular-Lab Eazy automatic synthesizer, Di Iorio V, Iori M, Donati C, Lanzetta V, Capponi PC, Rubagotti S, Dreger T, Kunkel F, Asti M, PP18 Synthesis and evaluation of fusarinine C-based octadentate bifunctional chelators for zirconium-89 labelling, Chuangyan Zhai, Christine Rangger, Dominik Summer, Hubertus Haas, Clemens Decristoforo, PP19 Fully automated production of [18F]NaF using a re-configuring FDG synthesis module., Suphansa Kijprayoon, Ananya Ruangma, Suthatip Ngokpol, Samart Tuamputsha, PP20 Extension of the Carbon-11 Small Labeling Agents Toolbox and Conjugate Addition, Ulrike Filp, Anna Pees, Carlotta Taddei, Aleksandra Pekošak, Antony D. Gee, Alex J. Poot, Albert D. Windhorst, PP21 In vitro studies on BBB penetration of pramipexole encapsulated theranostic liposomes for the therapy of Parkinson’s disease, Mine Silindir Gunay, A. Yekta Ozer, Suna Erdogan, Ipek Baysal, Denis Guilloteau, Sylvie Chalon, PP22 Factors affecting tumor uptake of 99mTc-HYNIC-VEGF165, Filippo Galli, Marco Artico, Samanta Taurone, Enrica Bianchi, Bruce D. Weintraub, Mariusz Skudlinski, Alberto Signore, PP23 Rhenium-188: a suitable radioisotope for targeted radiotherapy, Nicolas Lepareur, Nicolas Noiret, François Hindré, Franck Lacœuille, Eric Benoist, Etienne Garin, PP24 Preparation of a broad palette of 68Ga radiopharmaceuticals for clinical applications, Trejo-Ballado F, Zamora-Romo E, Manrique-Arias JC, Gama-Romero HM, Contreras-Castañon G, Tecuapetla-Chantes RG, Avila-Rodriguez MA, PP25 68Ga-peptide preparation with the use of two 68Ge/68Ga-generators, H. Kvaternik, D. Hausberger, C. Zink, B. Rumpf, R. M. Aigner, PP26 Assay of HEPES in 68Ga-peptides by HPLC, H. Kvaternik, D. Hausberger, B. Rumpf, R. M. Aigner, PP27 Preparation, in vitro and in vivo evaluation of a 99mTc(I)-Diethyl Ester (S,S)-Ethylenediamine- N,N´-DI-2-(3-Cyclohexyl) Propionic acid as a target-specific radiopharmaceutical, Drina Janković, Mladen Lakić, Aleksandar Savić, Slavica Ristić, Nadežda Nikolić, Aleksandar Vukadinović, Tibor J. Sabo, Sanja Vranješ-Đurić, PP28 90Y-labeled magnetite nanoparticles for possible application in cancer therapy, S. Vranješ-Đurić, M. Radović, D. Janković, N. Nikolić, G. F. Goya, P. Calatayud, V. Spasojević, B. Antić, PP29 Simplified automation of the GMP production of 68Ga-labelled peptides, David Goblet, Cristiana Gameiro, Neva Lazarova, PP30 Combining commercial production of multi-products in a GMP environment with Clinical & R&D activities, Cristiana Gameiro, Ian Oxley, Antero Abrunhosa, Vasko Kramer, Maria Vosjan, Arnold Spaans, PP31 99mTc(CO)3-labeling and Comparative In-Vivo Evaluation of Two Clicked cRGDfK Peptide Derivatives, Kusum Vats, Drishty Satpati, Haladhar D Sarma, Sharmila Banerjee, PP32 Application of AnaLig resin for 99mTc separation from molybdenum excess, Wojdowska W., Pawlak D.W., Parus L. J., Garnuszek P., Mikołajczak R., PP33 Constraints for selection of suitable precursor for one-step automated synthesis of [18F]FECNT, the dopamine transporter ligand, Pijarowska-Kruszyna J, Jaron A, Kachniarz A, Malkowski B, Garnuszek P, Mikolajczak R, PP34 Gamma scintigraphy studies with 99mTc- amoxicillin sodium in bacterially infected and sterile inflamed rats, Derya Ilem-Ozdemir, Oya Caglayan-Orumlu, Makbule Asikoglu, PP35 Preparation of 99mTc- Amoxicillin Sodium Lyophilized Kit, Derya Ilem-Ozdemir, Oya Caglayan-Orumlu, Makbule Asikoglu, PP36 Outfits of Tracerlan FXC-PRO for 11C-Labeling, Arponen Eveliina, Helin Semi, Saarinen Timo, Vauhkala Simo, Kokkomäki Esa, Lehikoinen Pertti, PP37 Microfluidic synthesis of ω-[18F]fluoro-1-alkynes, Mariarosaria De Simone, Giancarlo Pascali, Ludovica Carzoli, Mauro Quaglierini, Mauro Telleschi, Piero A. Salvadori, PP38 Automated 18F-flumazenil production using chemically resistant disposable cassettes, Phoebe Lam, Martina Aistleitner, Reinhard Eichinger, Christoph Artner, PP39 The effect of the eluent solutions (TBAHCO3, Kryptand K2.2.2) on the radiochemical yields of 18F-Fluoromethylcholine, Surendra Nakka, Hemantha Kumara MC, Al-Qahtani Mohammed, PP40 [68Ga]Radiolabeling of short peptide that has a PET imaging potentials, Al-Qahtani, Mohammed, Al-Malki, Yousif, PP41 Is validation of radiochemical purity analysis in a public hospital in a developing country possible?, N Mambilima, SM Rubow, PP42 Improved automated radiosynthesis of [18F]FEPPA, N. Berroterán-Infante, M. Hacker, M. Mitterhauser, W. Wadsak, PP43 Synthesis and initial evaluation of Al18F-RESCA1-TATE for somatostatin receptor imaging with PET, Uta Funke, Frederik Cleeren, Joan Lecina, Rodrigo Gallardo, Alfons M. Verbruggen, Guy Bormans, PP44 Radiolabeling and SPECT/CT imaging of different polymer-decorated zein nanoparticles for oral administration, Rocío Ramos-Membrive, Ana Brotons, Gemma Quincoces, Laura Inchaurraga, Inés Luis de Redín, Verónica Morán, Berta García-García, Juan Manuel Irache, Iván Peñuelas, PP45 An analysis of the quality of 68Ga-DOTANOC radiolabelling over a 3 year period, Trabelsi, M., Cooper M.S., PP46 In vivo biodistribution of adult human mesenchymal stem cells I (MSCS-ah) labeled with 99MTC-HMPAO administered via intravenous and intra-articular in animal model. Preliminary results, Alejandra Abella, Teodomiro Fuente, Antonio Jesús Montellano, Teresa Martínez, Ruben Rabadan, Luis Meseguer-Olmo, PP47 Synthesis of [18F]F-exendin-4 with high specific activity, Lehtiniemi P, Yim C, Mikkola K, Nuutila P, Solin O, PP48 Experimental radionuclide therapy with 177Lu-labelled cyclic minigastrin and human dosimetry estimations, von Guggenberg E, Rangger C, Mair C, Balogh L, Pöstényi Z, Pawlak D, Mikołajczak R, PP49 Synthesis of radiopharmaceuticals for cell radiolabelling using anion exchange column, Socan A, Kolenc Peitl P, Krošelj M, Rangger C, Decristoforo C, PP50 [68Ga]peptide production on commercial synthesiser mAIO, Collet C., Remy S., Didier R,Vergote T.,Karcher G., Véran N., PP51 Dry kit formulation for efficient radiolabeling of 68Ga-PSMA, D. Pawlak, M. Maurin, P. Garnuszek, U. Karczmarczyk, R. Mikołajczak, PP52 Development of an experimental method using Cs-131 to evaluate radiobiological effects of internalized Auger-electron emitters, Pil Fredericia, Gregory Severin, Torsten Groesser, Ulli Köster, Mikael Jensen, PP53 Preclinical comparative evaluation of NOTA/NODAGA/DOTA CYCLO-RGD peptides labelled with Ga-68, R. Leonte, F. D. Puicea, A. Raicu, E. A. Min, R. Serban, G. Manda, D. Niculae, PP54 Synthesizer- and Kit-based preparation of prostate cancer imaging agent 68Ga-RM2, Marion Zerna, Hanno Schieferstein, Andre Müller, Mathias Berndt, PP55 Synthesis of pancreatic beta cell-specific [18F]fluoro-exendin-4 via strain-promoted aza-dibenzocyclooctyne/azide cycloaddition, Cheng-Bin Yim, Kirsi Mikkola, Pirjo Nuutila, Olof Solin, PP56 Automated systems for radiopharmacy, D. Seifert, J. Ráliš, O. Lebeda, PP57 Simple, suitable for everyday routine use quality control method to assess radionuclidic purity of cyclotron-produced 99mTc, Svetlana V. Selivanova, Helena Senta, Éric Lavallée, Lyne Caouette, Éric Turcotte, Roger Lecomte, PP58 Effective dose estimation using Monte Carlo simulation for patients undergoing radioiodine therapy, Marina Zdraveska Kochovska, Emilija Janjevik Ivanovska, Vesna Spasic Jokic, PP59 Chemical analysis of the rituximab radioimmunoconjugates in lyophilized formulations intended for oncological applications, Darinka Gjorgieva Ackova, Katarina Smilkov, Petre Makreski, Trajče Stafilov, Emilija Janevik-Ivanovska, PP61 The need and benefits of established radiopharmacy in developing African countries, Aschalew Alemu, Joel Munene Muchira, David Mwanza Wanjeh, Emilija Janevik-Ivanovska, PP62 University Master Program of Radiopharmacy – step forward for Good Radiopharmacy Education, Emilija Janevik-Ivanovska, Zoran Zdravev, Uday Bhonsle, Osso Júnior João Alberto, Adriano Duatti, Bistra Angelovska, Zdenka Stojanovska, Zorica Arsova Sarafinovska, Darko Bosnakovski, Darinka Gorgieva-Ackova, Katarina Smilkov, Elena Drakalska, Meera Venkatesh, Rubin Gulaboski, PP63 Synthesis and preclinical validations of a novel 18F-labelled RGD peptide prepared by ligation of a 2-cyanobenzothiazole with 1,2-aminothiol to image angiogenesis., Didier J. Colin, James A. H. Inkster, Stéphane Germain, Yann Seimbille

Accelerating climate change and increased economic and environmental interests in permafrost-affected regions have resulted in an acute need for more directed permafrost research. In June 2014, 88 early career researchers convened to identify future priorities for permafrost research. This multidisciplinary forum concluded that five research topics deserve greatest attention: permafrost landscape dynamics, permafrost thermal modeling, integration of traditional knowledge, spatial distribution of ground ice, and engineering issues. These topics underline the need for integrated research across a spectrum of permafrost-related domains and constitute a contribution to the Third International Conference on Arctic Research Planning (ICARP III)., Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe, 490

A Boolean value of given a priori probability distribution is transmitted to a deciding agent by several processes. Each process fails independently with given probability, and faulty processes behave in a Byzantine way. A deciding agent has to make a decision concerning the transmitted value on the basis of messages obtained by processes. We construct a deterministic decision strategy which has the provably highest probability of correctness. It computes the decision in time linear in the number of processes. Decision optimality may be alternatively approached from a local, rather than global, point of view. Instead of maximizing the total probability of correctness of a decision strategy, we may try to find, for every set of values conveyed by processes, the conditionally most probable original value that could yield this set. We call such a strategy locally optimal, as it locally optimizes the probability of a decision, given a set of relayed values, disregarding the impact of such a choice on the overall probability of correctness. We construct a locally optimal decision strategy which again computes the decision value in time linear in the number of processes. We establish the surprising fact that, in general, local probability maximization may lead to a decision strategy which does not have the highest probability of correctness. However, if the probability distribution of the Boolean value to be conveyed is uniform, and all processes have the same failure probability smaller than 12, this anomaly does not occur. We first design and analyze our strategies in the synchronous setting and then show how they should be modified to work in asynchronous systems.

The chromatin structure of RNA polymerase I - transcribed ribosomal DNA (rDNA) is well characterized. In most organisms, i.e., lower eukaryotes, plants, and animals, only a fraction of ribosomal genes are transcriptionally active. At the chromatin level inactive rDNA is assembled into arrays of nucleosomes, whereas transcriptionally active rDNA does not contain canonical nucleosomes. To separate inactive (nucleosomal) and active (non-nucleosomal) rDNA, the technique of psoralen photocrosslinking has been used successfully both in vitro and in vivo. In Saccharomyces cerevisiae, the structure of rDNA chromatin has been particularly well studied during transcription and during DNA replication. Thus, the yeast rDNA locus has become a good model system to study the interplay of all nuclear DNA processes and chromatin. In this review we focused on the studies of chromatin in ribosomal genes and how these results have helped to address the fundamental question: What is the structure of chromatin in the coding regions of genes?Key words: active chromatin, FACT, lexosome, psoralen, photo-crosslinking, rDNA, RNA polymerase I.

We construct and analyze a fast broadcasting algorithm working in the presence of Byzantine component faults. Such faults are particularly difficult to deal with, as faulty components may behave arbitrarily (even maliciously) as transmitters, by either blocking, rerouting, or altering transmitted messages in a way most detrimental to the broadcasting process. We assume that links and nodes of a communication network are subject to Byzantine failures, and that faults are distributed randomly and independently, with link failure probability p and node failure probability q, these parameters being constant and satisfying the inequality (1 - p)2(1 - q) > 1/2. A broadcasting algorithm, working in an n-node network, is called almost safe if the probability of its correctness is at least 1 - 1/n, for sufficiently large n. Thus the robustness of the algorithm grows with the size of the network. Our main result is the design and analysis of an almost safe broadcasting algorithm working in time O( log 2 n) and using O(n log n) messages in n-node networks. Under a stronger assumption on failure probability parameters, namely (1 - p)2(1 - q)2 > 1/2, our algorithm can be modified to work in time O( log 2 n/ log log n), also using O(n log n) messages. The novelty of our algorithm is that it can cope with the most difficult type of faults, potentially affecting all components of the network (both its links and nodes), and that it is simultaneously robust and efficient.

Convenient approaches for the synthesis of DOTHA2 and NOTHA2, two cyclic bifunctional chelates (BFCs) bearing hydroxamate arms, have been developed. These novel BFCs coordinate (64)Cu with fast kinetics at room temperature in a wide range of concentrations and pH. The corresponding radiochemical complexes showed high stability, low residual activity in various tissues, and fast clearance in normal mice. The ability to conjugate DOTHA2 to both a small peptide and a large protein is also reported.

Background The estrogen receptor α (ERα) is known to play an important role in the modulation of tumor response to hormone therapy. In this work, the effect of different hormone therapies on tumors having different ERα expression levels was followed up in vivo in a mouse model by PET imaging using 2-deoxy-2-[18F]fluoro-d-glucose (FDG) and [11C]-methionine ([11C]-MET). A new model of MC7-L1 ERα-knockdown (ERαKD) tumor cell lines was designed as a negative estrogen receptor control to follow up the effects of changes in ERα expression on the early metabolic tumor response to different hormone therapies. Methods MC7-L1 (ER+) and MC7-L1 ERα-knockdown cell lines were implanted subcutaneously in Balb/c mice and allowed to grow up to 4 mm in diameter. Animals were separated into 4 groups (n = 4 or 5) and treated with a pure antiestrogen (fulvestrant), an aromatase inhibitor (letrozole), a selective estrogen receptor modulator (tamoxifen), or not treated (control). Tumor metabolic activity was assessed by PET imaging with FDG and [11C]-MET at days 0 (before treatment), 7, and 14 after the treatment. Tumor uptake of each radiotracer in %ID/g was measured for each tumor at each time point and compared to tumor growth. Quantitative PCR (qPCR) was performed to verify the expression of breast cancer-related genes (ERα, ErbB2, progesterone receptor (PR), and BRCA1) in each tumor cell lines. Results While both ER+ and ERαKD tumors had similar uptake of both radiotracers without treatment, higher uptake values were generally seen in ERαKD tumors after 7 and 14 days of treatment, indicating that ERαKD tumors behave in a similar fashion as hormone-unresponsive tumors. Furthermore, the ERα-specific downregulation induced a slight PR expression decrease and overexpression of BRCA1 and ErbB2. Conclusion The results indicate that the proposed ER+/ERαKD tumor-bearing mouse model is suitable to test pure antiestrogen and aromatase inhibitor therapies in vivo in a preclinical setting and could help to elucidate the impact of ERα levels on tumor response to hormone therapy.

We consider the problem of locating a black hole in a synchronous, anonymous, and unoriented torus network using mobile agents. A black hole is a harmful network node that destroys any agent visiting it without leaving any trace. The objective is to locate the black hole using as few agents as possible. We present here an almost optimal deterministic algorithm for synchronous (partially) unoriented tori using five scattered agents with constant memory and three identical tokens. We also study the exploration problem of a safe (i.e., without black holes) unoriented torus. While it has been previously shown that there is no universal algorithm for one agent with constant memory and any constant number of tokens which can explore all cubic planar graphs, we give here the first algorithm which enables a finite automaton with two tokens to explore (without termination detection) any totally unoriented torus and we prove optimality on the number of tokens.

Introduction The purpose of this study was to develop a noninvasive model in tumor-bearing mice to investigate the use of 16α-[ 18 F]fluoro-17β-estradiol (FES) positron emission tomography (PET) imaging as a tool to discriminate between tumors having different estrogen receptor (ER) α status. Methods MC7-L1 and MC4-L2 murine mammary adenocarcinoma cell lines (ER+) received a small hairpin RNA targeting the ERα gene by lentiviral infection. In vitro assessment of ERα levels of the new cell lines (MC7-L1 and MC4-L2 ERα-knockdown; ERαKD), compared to the parental cell lines, was performed by immunoblotting (−75% ERα protein) and binding assays (−50% estrogen binding). These cell lines were implanted subcutaneously in Balb/c mice and allowed to grow up to a volume of at least 20 mm 3 . FES and [ 18 F]fluorodeoxyglucose (FDG) PET images were acquired to measure FES and FDG uptake in the various tumors. Results FES uptake as assessed by PET imaging was 1.06±0.21 percent injected dose per gram of tissue (%ID/g) for MC7-L1 tumors and 0.47±0.08 %ID/g for MC7-L1 ERαKD tumors. MC4-L2 tumors had a FES uptake of 1.03±0.30 %ID/g, whereas its ERαKD equivalent was 0.51±0.19 %ID/g. Each ERαKD tumor had a significantly lower %ID/g value, by ∼50%, than its ER+ counterpart. Biodistribution studies confirmed these findings and gave %ID/g values that were not significantly different from PET imaging data. FDG PET showed no significant uptake difference between the ER+ and ERαKD tumors, indicating that the metabolic phenotype of the ERαKD cell lines was not altered. Conclusion FES PET imaging was able to reliably differentiate between tumors having differences in their ERα expression in vivo, in a mouse model. Quantitative data obtained by FES PET were in concordance with biodistribution studies and in vitro assays. It is concluded that FES PET imaging can likely be used to monitor subtle ER status changes during the course of hormone therapy.

In this paper, we address the problem of broadcasting in a wireless sensor network under a novel communication model: the swamping communication model. In this model, nodes communicate only with those nodes at distance greater than s and at most r from them. We consider networks of unknown topology of diameter D, with a lower bound a on the geometric distance between nodes and a parameter g = 1/α (granularity). We present broadcast algorithms for networks of nodes placed on the line and on the plane with respective time complexities O(D/l + g2) and O(Dg/l + g4), where l ∈ Θ(max{(1 - s), α}).

We study the feasibility and time of communication in random geometric radio networks, where nodes fail randomly with positive correlation. We consider a set of radio stations with the same communication range, distributed in a random uniform way on a unit square region. In order to capture fault dependencies, we introduce the ranged spotmodel in which damaging events, called spots, occur randomly and independentlyon the region, causing faults in all nodes located within distance sfrom them. Node faults within distance 2sbecome dependent in this model and are positively correlated. We investigate the impact of the spot arrival rate on the feasibility and the time of communication in the fault-free part of the network. We provide an algorithm which broadcasts correctly with probability 1 ? ?in faulty random geometric radio networks of diameter Din time O(D+ log1/?).

The aim of this paper is to study communication in networks where nodes fail in a random dependent way. In order to capture fault dependencies, we introduce the neighborhood fault model, where damaging events, called spots, occur randomly and independently with probability p at nodes of a network, and cause faults in the given node and all of its neighbors. Faults at distance at most 2 become dependent in this model and are positively correlated. We investigate the impact of spot probability on feasibility and time of communication in the fault-free part of the network. We show a network which supports fast communication with high probability, if p = 1/c log n. We also show that communication is not feasible with high probability in most classes of networks, for constant spot probabilities. For smaller spot probabilities, high probability communication is supported even by bounded degree networks. It is shown that the torus supports communication with high probability when p decreases faster than 1/n1/2, and does not when p ? 1/O(n1/2). Furthermore, a network built of tori is designed, with the same faulttolerance properties and additionally supporting fast communication. We show, however, that networks of degree bounded by a constant d do not support communication with high probability, if p ? 1/O(n1/d). While communication in networks with independent faults was widely studied, this is the first analytic paper which investigates network communication for random dependent faults.

The purpose of this study was to evaluate the effects of 2 anesthetic agents on myocardial perfusion and coronary reserve in rats under resting and stress conditions with small animal PET.Twenty-four rest/stress studies were performed in 6 rats. Each animal received all 4 possible combinations of anesthetic agents (propofol, isoflurane) and pharmacologic stress agents (dobutamine, adenosine) to increase myocardial perfusion. For each stress or rest study, a 10-min dynamic acquisition was performed in list mode with 185 MBq of (13)N-NH(3). Data analysis was performed according to a 3-compartment myocardial blood flow model. Pharmacologic stimulation by either dobutamine or adenosine was performed to increase myocardial perfusion.The perfusion values (mean +/- SD) for the various experimental conditions were as follows: propofol/dobutamine, 7.8 +/- 2.4 mL/g/min (rest, 3.7 +/- 0.8 mL/g/min; mean +/- SD); isoflurane/dobutamine, 9.3 +/- 3.1 mL/g/min (rest, 4.3 +/- 1.0 mL/g/min); propofol/adenosine, 6.8 +/- 1.7 mL/g/min (rest, 3.2 +/- 0.4 mL/g/min); and isoflurane/adenosine, 5.2 +/- 1.3 mL/g/min (rest, 3.7 +/- 0.7 mL/g/min). All perfusion data showed a significant increase after pharmacologic stimulation relative to baseline (P0.05). The coronary reserve (mean +/- SD) measured by PET was slightly lower with the combination of isoflurane and adenosine (1.4 +/- 0.5) than with propofol and adenosine (2.1 +/- 0.5).Noninvasive quantitative measurements of myocardial perfusion in small animals at rest and during stress are feasible using PET. Evaluation of the coronary reserve must take into account the initial state of the anesthetized animal. The coronary reserve could be measured with both anesthetic agents using either dobutamine or adenosine stimulation.