Biodistribution of 18F-FES in Patients with Metastatic ER+ Breast Cancer Undergoing Treatment with Rintodestrant (G1T48), a Novel Selective ER Degrader.

16α-18F-fluoro-17ß-estradiol (18F-FES) is a PET tracer characterizing the expression of the estrogen receptor (ER). Because therapy can interfere with the kinetics and biodistribution of 18F-FES, the aim of this study was to describe the biodistribution of 18F-FES in patients with metastatic ER-positive (ER+) breast cancer undergoing treatment with rintodestrant (G1T48), a novel selective ER degrader. Methods: Eight patients underwent 18F-FES PET/CT imaging at baseline, 4-6 wk during treatment with rintodestrant (interim), and after treatment. After intravenous administration of 200 MBq (±10%) of 18F-FES, a 50-min dynamic PET/CT scan of the thorax was obtained, followed by a whole-body PET/CT scan 60 min after injection. Blood samples were drawn for measuring whole blood and plasma activity concentration and the parent fraction of 18F-FES. Volumes of interest were placed in the aorta ascendens and in healthy tissues on both dynamic and whole-body PET scans. SUVs and target-to-blood ratios (TBRs) were calculated. Areas under the curve (AUCs) of input functions and time-activity curves were calculated as a measure of uptake in different regions. Results:18F-FES concentration in whole blood (and plasma) significantly (P < 0.05) increased at interim with median AUCs of 96.6, 116.6, and 110.3 at baseline, interim, and after treatment, respectively. In ER-expressing tissues, that is, the uterus and the pituitary gland, both SUV and TBR showed high 18F-FES uptake at baseline, followed by a decrease in uptake at interim (uterus: SUV -50.6% and TBR -58.5%; pituitary gland: SUV -39.0% and TBR -48.3%), which tended to return to baseline values after treatment (uterus: SUV -21.5% and TBR -37.9%; pituitary gland: SUV -14.2% and TBR -26.0%, compared with baseline). In other healthy tissues, tracer uptake remained stable over the 3 time points. Conclusion: The biodistribution of 18F-FES is altered in blood and in ER-expressing healthy tissues during therapy with rintodestrant. This indicates that rintodestrant alters the kinetics of the tracer, possibly affecting interpretation and quantification of 18F-FES uptake. Of note, 6 d or more after treatment with rintodestrant ended, the biodistribution returned to baseline values, consistent with recovery of ER availability after washout of the drug.

Effects of land use on infestation and parasitism rates of cabbage seed weevil in oilseed rape.

BACKGROUND: This study investigated how infestation rates of an important oilseed rape pest, the cabbage seed weevil (Ceutorhynchus obstrictus) and rates of parasitization by its parasitoids are affected by land use, up to 1000 m from 18 focal fields. RESULTS: The mean proportion of C. obstrictus-infested pods per plant was 8% (2-19.5%). Infestation rates were higher if the adjacent habitat was a herbaceous semi-natural habitat than if it was either another crop or a woody habitat. Infestation rates were positively related to the area of herbaceous semi-natural vegetation, permanent grassland and wheat (which followed oilseed rape in the crop rotation) at a spatial scale of at least 1 km. The mean parasitism rate of C. obstrictus larvae was 55% (8.3-87%), sufficient to provide efficient biocontrol. Parasitism rates were unrelated to adjacent habitats, however, they were positively related to the presence of herbaceous linear elements in the landscape and negatively related to permanent grasslands at a spatial scale of 200 m. CONCLUSION: Proximity of herbaceous elements increased both infestation rates and parasitism, while infestation was also related to landscape factors at larger distances. The findings provide an empirical basis for designing landscapes that suppress C. obstrictus, at both field and landscape scales. © 2018 Society of Chemical Industry.

Dynamics of Supercooling Ability and Cold Tolerance of the Alder Beetle (Coleoptera: Chrysomelidae).

Agelastica alni L. (Coleoptera: Chrysomelidae) is a common beetle pest of alder trees (Alnus incana L.) in forests and parks across Estonia. The supercooling ability and capacity to survive low temperature exposure changes temporally. Relatively high unimodal supercooling point (SCP) levels (with a mean value of -6 to -8°C) were characteristic of the beetles in September during their diapause induction period, in April when the beetles had terminated their diapause development and in May when they started to reproduce. During their deep diapause period the SCPs of beetles had a bimodal distribution. Some beetles decreased their SCPs to -14 to -19°C while others retained a high SCP value of -6 to -8°C. Most vulnerable to low temperature were overwintered active beetles in May; after 1 h exposure their LTemp50 (median lethal temperature) was -6.3°C. In September with the onset of diapause tolerance of beetles started to increase, LTemp50 = -7.7°C. Beetles were most cold tolerant during their deep diapause period with LTemp50 < -12.0°C. A. alni beetles use one of two different strategies for overwintering, some are freeze-tolerant while others are freeze-avoidant. The freeze-avoidant beetles with low SCP (-12 to -15°C) acquired greater cold tolerance than those with higher SCP (-6 to -8°C), with LTemp50 = -13.7°C and LTemp50 = -11°C, respectively.

The Nutritive Value of Organic and Conventional White Cabbage (Brassica Oleracea L. Var. Capitata) and Anti-Apoptotic Activity in Gastric Adenocarcinoma Cells of Sauerkraut Juice Produced Therof.

White cabbage is one of the most important vegetables grown both in Poland and worldwide. Cabbage contains considerable amounts of bioactive compounds such as glucosinolates, vitamin C, carotenoids, and polyphenols. Some experiments indicate that vegetables from organic production contain more bioactive compounds than those from conventional production, however, only a few studies have been conducted on cruciferous plants. The presented study has proved that organic fresh cabbage, compared to the conventional one, contained significantly less total flavonoids in both years of experiments (3.95 ± 0.21 mg/100 g FW and 3.71 ± 0.33 mg/100 g FW), several flavonoid compounds, total chlorophylls (1.51 ± 0.17 mg/100 g FW and 1.30 ± 0.22 mg/100 g FW) carotenoids, nitrites (0.55 ± 0.04 mg/kg FW and 0.45 ± 0.02 mg/kg FW), and nitrates (0.50 ± 0.13 g/kg FW and 0.47 ± 0.11 g/kg FW). The organic sauerkraut juice, compared to the conventional one, contained significantly more total polyphenols (5.39 ± 0.22 mg/100 g FW and 9.05 ± 1.10 mg/100 g FW) as well as several flavonoids. Only CONV sauerkraut juice produced with the highest N level of fertilization induced a statistical significant increase of the level of necrosis of human stomach gastric adenocarcinoma cell line AGS.

Changes in Polyphenols Contents and Antioxidant Capacities of Organically and Conventionally Cultivated Tomato (Solanum lycopersicum L.) Fruits during Ripening.

Polyphenols of fruits and vegetables form an important part of human dietary compounds. Relatively little is known about accumulation of phenolics during fruits ripening process. The goal of this work was to study the changes in antioxidant activity and in content of 30 polyphenols during ripening of tomato fruits. Five organically and conventionally grown tomato cultivars were investigated at three different ripening stages. Phenolic compounds were extracted with methanol and extracts were analyzed by HPLC-DAD-MS/MS. During ripening, four different changing patterns were observed: (1) high level in green fruits with minimal changes; (2) continuous increase with maximum level in red-ripe fruits; (3) decrease; (4) increase and achieving maximum level at half-ripe stage. Similar change patterns were found for organic and conventional fruits. The accumulation patterns of phenolic compounds were similar in standard-type tomatoes but differed in several cases in cherry-type cultivar. Although contents of some polyphenols decreased during ripening, total phenolics and free radical scavenging activity increased in all studied cultivars and in case of both cultivation modes. The changes in content of phenolic compounds during ripening were greatly influenced by cultivars, but cultivation mode had only minor impact on dynamics in polyphenols contents in tomato fruits.

89Zr-cetuximab PET imaging in patients with advanced colorectal cancer.

Monoclonal antibodies (mAbs) against the epidermal growth factor receptor (EGFR) are used in the treatment of advanced colorectal cancer (mCRC). Approximately 50% of patients benefit despite patient selection for RAS wild type (wt) tumors. Based on the hypothesis that tumor targeting is required for clinical benefit of anti-EGFR treatment, biodistribution and tumor uptake of (89)Zr-cetuximab by Positron Emission Tomography (PET), combining the sensitivity of PET with the specificity of cetuximab for EGFR was evaluated. Ten patients with wt K-RAS mCRC received 37 ± 1 MBq (89)Zr-cetuximab directly (<2 h) after the first therapeutic dose of cetuximab. PET-scans were performed from 1 hour to 10 days post injection (p.i.). Biodistribution was determined for blood and organs. Uptake in tumor lesions was quantified by Standardized Uptake Value (SUV) and related to response. In 6 of 10 patients (89)Zr-cetuximab uptake in tumor lesions was detected. Four of 6 patients with (89)Zr-cetuximab uptake had clinical benefit, while progressive disease was observed in 3 of 4 patients without (89)Zr-cetuximab uptake. Taken together, tumor uptake of 89Zr-cetuximab can be visualized by PET imaging. The strong relation between uptake and response warrants further clinical validation as an innovative selection method for cetuximab treatment in patients with wt RAS mCRC.

Beetroot (Beta vulgaris L.) and naturally fermented beetroot juices from organic and conventional production: metabolomics, antioxidant levels and anticancer activity.

BACKGROUND: The aim of the paper was to determine the level of antioxidants and metabolomic fingerprinting in both raw beetroots and naturally fermented beetroot juices from organic (ORG) versus conventional (CONV) production. In addition, the anticancer properties of the fermented beetroot juices were evaluated. RESULTS: The obtained results showed that ORG fresh beetroots contained significantly more dry matter, vitamin C and some individual phenolic compounds than CONV beetroots. The content of total phenolic acids was significantly higher in CONV beetroots compared with the ORG ones. The level of flavonoids was similar in ORG and CONV beetroots. There were only slight differences in the chemical composition of ORG and CONV beetroot juices. Metabolomic analysis provided a possibility to distinguish clearly between ORG and CONV fermented beetroot juices. However, this method was less useful in the case of fresh whole beetroots. It was found that anticancer activity was stronger in the case of ORG fermented juices when compared with CONV ones. CONCLUSION: The obtained results indicate that ORG- and CONV-produced beetroots and fermented beetroot juices have different chemical properties and different impacts on cancer cells. It is necessary to continue research on this topic in order to confirm and understand the achieved results.

Three-year comparative study of polyphenol contents and antioxidant capacities in fruits of tomato (Lycopersicon esculentum Mill.) cultivars grown under organic and conventional conditions.

In the present study, four tomato cultivars were grown under organic and conventional conditions in separate unheated greenhouses in three consecutive years. The objective was to assess the influence of the cultivation system on the content of individual polyphenols, total phenolics, and antioxidant capacity of tomatoes. The fruits were analyzed for total phenolic content by the Folin-Ciocalteau method and antioxidant capacity by the DPPH free radical scavenging assay. Individual phenolic compounds were analyzed using HPLC-DAD-MS/MS. Among 30 identified and quantified polyphenols, significantly higher contents of apigenin acetylhexoside, caffeic acid hexoside I, and phloretin dihexoside were found in all organic samples. The content of polyphenols was more dependent on year and cultivar than on cultivation conditions. Generally, the cultivation system had minor impact on polyphenols content, and only a few compounds were influenced by the mode of cultivation in all tested cultivars during all three years.

Effects of Fastac 50 EC on bumble bee Bombus terrestris L. respiration: DGE disappearance does not lead to increasing water loss.

Sublethal effects of pesticides in insects can be observed through physiological changes, which are commonly estimated by metabolic rate and respiratory patterns, more precisely by the patterns of discontinuous gas-exchange (DGE) cycles. The aim of the present research was to study the effect of some low concentrations of Fastac 50 EC on the cycles of CO(2) release and respiratory water loss rates (WLR) in bumble bee Bombus terrestris L. foragers. Bumble bees were dipped into 0.004% and 0.002% Fastac 50 EC solution. Flow-through respirometry was used to record the respiration and WLR 3h before and after the treatment. The respirometry was combined with infrared actography to enable simultaneous recording of abdominal movements. Our results show that Fastac 50 EC has an after-effect on bumble bee respiratory rhythms and muscle activity but does not affect WLR. Treatment with 0.004% Fastac 50 EC solution resulted in disappearance of the respiration cycles; also the lifespan of treated bumble bees was significantly shorter. Treatment with 0.002% Fastac 50 EC solution had no significant effect on respiration patterns or longevity. We found no evidence for the DGE cycles functioning as a water saving mechanism.

Oxygen convective uptakes in gas exchange cycles in early diapause pupae of Pieris brassicae.

Oxygen convective uptakes in gas exchange cycles were directly recorded in early diapause pupae of Pieris brassicae L. (Lepidoptera; Pieridae) by means of O2 coulometric respirometry. This method was combined with flow-through CO2 respirometry, the two systems being switchable one to the other. During recording with both systems, measurements were also taken with infrared actography. The pupae displayed short discontinuous gas exchange cycles lasting 40-70 min. No true C phase was found by flow-through measurements; instead, flutter opening of the spiracles with discrete convective O2 uptakes began shortly after the O phase whereas CO2 release was suppressed by the inward directed passive suction ventilation. The F phase was characterized by a series of small CO2 bursts (flutter events). Between these bursts, novel sub-phase `miniflutter' was observed, which consisted of six to 10 miniature inspirations without any CO2 emission. During the flow-through measurements, oxygen convective uptakes were indirectly recorded by the infrared actograph as sudden extensions (lengthening) of the abdominal segments at each spiracular microopening.

Effect of selenium treatment on mineral nutrition, bulb size, and antioxidant properties of garlic (Allium sativum L.).

Foliar selenium (Se) treatment of garlic at concentrations of 10, 50, and 100 µg of Se/mL was carried out in open field conditions in 2008 and 2009 in Estonia. Bulb weight and yield structure, content of total Se, S, N, P, K, Ca, and Mg, ascorbic acid content (AAC), pungency, total phenolics, and total antioxidant capacity (TAC) were determined. The highest level of Se decreased total S, K, and Ca in both years; no negative impact on bulb weight was observed. In 2009 Se10 treatment had significantly more bulbs with the largest diameter compared to the other treatments. In 2008, the AAC was decreased by Se50 and the content of total phenolics by all Se treatments; however, TAC was increased. Foliar Se fertilization of garlic at rates of 10-50 µg of Se/mL can be recommended to increase the number of large bulbs and increase bulb antioxidant capacity.

Electrophysiological identification of hygroreceptor neurons from the antennal dome-shaped sensilla in the ground beetle Pterostichus oblongopunctatus.

This study gives the first electrophysiological evidence of hygroreceptors in carabids. Extracellular recordings from the antennal dome-shaped sensilla of the carabid beetle Pterostichus oblolongopunctatus (Coleoptera, Carabidae) clearly show the presence of moist and dry neuron antagonistically responding to humidity changes. The cold neuron of the same sensillum did not respond to changes in humidity. For the first time, we demonstrate that the binary system of two antagonistic hygroreceptor neurons discriminates differences between steady-state humidity levels more sensitively than either neuron separately. Another advantage of the binary system is that it guarantees immediate and strong phasic-tonic response to rapid humidity changes in either direction. In the hygrosensing system of carabids, this would allow detection of subtle step-changes in humidity with greater sensitivity than differences in steady-state values of humidity. Thus, construction of the hygrosensing system with opposing receptor neurons may allow insects to detect environmental humidity differences critical for their habitat and microhabitat selection, and survival with great precision.

Leaf rust induced volatile organic compounds signalling in willow during the infection.

Plants are known to emit volatile organic compounds (VOC) in response to various biotic or abiotic stresses. Although the VOC emission in the case of insect attacks is well described, there is only little known about the impact of pathogens on plant emission. In the present study, we used a willow-leaf rust system to describe the effects of a biotrophic fungal infection on the VOC emission pattern of willow leaves. We detected that isoprene emissions from rust-infected leaves decreased threefold compared to control. The total monoterpene emissions did not change although a stress-signalling compound (Z)-beta-ocimene showed an increase in infected plants on several days. The infection also increased the emission of sesquiterpenes and lipoxygenase products (LOX) by factors of 175-fold and 10-fold, respectively. The volatile emission signals showed two clear peaks during the experiment. At 6, 7 and 12 days post-infection (dpi), the relative volatile emission signal increased to about sixfold compared to uninfected plants. These time points are directly connected to rust infection since at 6 dpi the first rust pustules appeared on the leaves and at 12 dpi necrosis had developed around several pustules. We present correlations between LOX and sesquiterpene emission signals, which suggest at least two different steps in eliciting the volatile emission.

Spike bursts generated by the thermosensitive (cold) neuron from the antennal campaniform sensilla of the ground beetle Platynus assimilis.

Responses of the antennal thermosensitive neuron of the ground beetle Platynus assimilis to warming from 20 to 50 degrees C were measured and analysed. During warming, neurons switched from regular spiking to bursting. ISI analysis showed that the number of spikes in the burst and spike frequency within the burst were temperature dependent and may precisely encode unfavourably or dangerously high temperatures in a graded manner. In contrast, regular spikes of the neuron encode moderate temperatures at 20-30 degrees C. The threshold temperature of spike bursting varied in different neurons from 25 to 47 degrees C. As a result, the number of bursting neurons increased with temperature increase. Therefore, in addition to the burst characteristics, the total number of bursting neurons may also contain useful information on external temperature. A relationship between the spike bursts and locomotor activity of the beetles was found which may have importance in behavioural thermoregulation of the species. At 44.4+/-0.6 degrees C, first indications of partial paralysis (of the hind legs) were observed. We emphasize, that in contrast to various sensory systems studied, the thermoreceptor neuron of P. assimilis has a stable and continuous burst train, no temporal information is encoded in the timing of the bursts.

Electrophysiological identification of the sugar cell in antennal taste sensilla of the predatory ground beetle Pterostichus aethiops.

By single sensillum tip recording technique, in addition to the salt and pH cells found in antennal taste sensilla of some ground beetles earlier, the third chemosensory cell of four innervating these large sensilla was electrophysiologically identified as a sugar cell in the ground beetle Pterostichus aethiops. This cell generated action potentials of considerably smaller amplitude than those of the salt and pH cells, and phasic-tonically responded to sucrose and glucose over the range of 1-1000 mM tested. Responses were concentration dependent, with sucrose generating more spikes than glucose. During the first second of the response, maximum rates of firing of the sugar cell reached up to 19 and 37 imp/s when stimulated with 1000 mM glucose and sucrose, respectively. Three to four seconds later, the responses decreased close to zero. Both sugars are important in plant carbohydrate metabolism. These ground dwelling insects may come into contact with live and decayed plant material everywhere in their habitat including their preferred overwintering sites in brown-rot decayed wood. In conclusion, we hypothesize that high content of soluble sugars in their overwintering sites and refugia is unfavourable for these ground beetles, most probably to avoid contact with dangerous fungi.

A new method for electrophysiological identification of antennal pH receptor cells in ground beetles: the example of Pterostichus aethiops (Panzer, 1796) (Coleoptera, Carabidae).

The responses of antennal taste sensilla of the ground beetle Pterostichus aethiops to 100mM Na(+)-salts and their mixtures with 1 and 10mM NaOH were compared. An increase in pH by 0.3-0.6 units in 100mM Na(+)-salt solutions, caused by the content of 1mM NaOH, was too small, except for alkaline Na(2)HPO(4), to influence the firing rate of the cation cell and pH cell significantly. However, different sensitivity of the two cells to increased pH was clearly demonstrated when the concentration of NaOH in 100mM stimulating salt solutions was increased to 10mM. Increasing pH by 1.2-2 units caused the 1st s firing rate to increase by 140-1050% and 0-26% in the pH cell and cation cell, respectively. Compared to the buffer series method used for identification of the pH receptors in ground beetles earlier, considerably stronger responses of the pH cell to a similar increase in pH were observed when the NaOH method was used for testing. At the same time, undesirable changes in salt ions concentration that occur when stimulating solutions differing by 1-2 pH units are prepared were much smaller using the latter method. Behavioural and ecological relevance of the results is discussed.

Responses of antennal campaniform sensilla to rapid temperature changes in ground beetles of the tribe platynini with different habitat preferences and daily activity rhythms.

Responses of temperature sensitive (cold) cells from the antenna of ground beetles (tribe Platynini) were compared in species with different ecological preferences and daily activity rhythms. Action potential rates were characterized at various temperatures (ranges 23-39 degrees C) and during rapid changes in it (Deltat=0.5-15 degrees C). The stationary firing frequencies were nearly twice as high in eurythermic open field ground beetles Agonum muelleri and Anchomenus dorsalis (firing rates ranging from 22 to 47imp/s) than in a stenothermic forest species Platynus assimilis. In the eurythermic species, the firing rate did not significantly depend on temperature (Anchomenus dorsalis range of 23-27 degrees C and Agonum muelleri range of 23-33 degrees C) but plots of firing rate versus temperature showed rapid declines when lethally high temperatures were approached. In contrast, a nearly linear decline of the firing rate/temperature curve was observed in Platynus assimilis. Responses to rapid temperature decreases were also considerably higher in eurythermic species. Both the peak frequency of the initial burst (maximum 420-650Hz) as well as the sustained discharge in the first 4s of the response were higher than in Platynus assimilis. Long silent periods, lasting up to several seconds, that occurred at the beginning of the response to rapid warming were significantly shorter in Agonum muelleri and Anchomenus dorsalis compared to Platynus assimilis. These findings suggest that the responses of thermoreceptors to temperature changes may be correlated with specific ecological preferences.

Electrophysiological responses to salts from antennal chaetoid taste sensilla of the ground beetle Pterostichus aethiops.

Antennal gustatory sensilla of the ground beetle Pterostichus aethiops (Pz., 1797) (Coleoptera, Carabidae) respond to salts, the three sensory cells, A-, B- and C-cells, producing action potentials that are distinguished by differences in their shape, amplitude, duration and polarity of spikes. The B-cell (salt cell) was highly sensitive to both ionic composition and concentration of the tested nine salt solutions showing phasic-tonic type of reaction with a pronounced phasic component. The stimulating effect was dominated by the cations involved, and in most cases, monovalent cations were more effective stimuli than divalent cations. Salt concentration/response relations were tested with NaCl at 1, 10, 100 and 1000 mmol l(-1): mean firing rates increased from 0.8 to 44 spikes per first second of the response, respectively. The pH value of the stimulating solutions also influenced the B-cell rate of firing. By contrast, the pH level of stimulus solutions influenced the A-cells' phasic-tonic response more than the ionic composition or concentration of these solutions. Compared to a standard 100 mmol l(-1) salt (NaCl) solution (pH 6.3), alkaline solutions of the salts NaCH3COO, Na2HPO4 and Na2B4O7 (pH 7.9, 8.5 and 9.3, respectively, all 100 mmol l(-1)) induced remarkably stronger responses in the A-cell. On the other hand, the reaction to an acid solution of NaH2PO4 (pH 4.5, 100 mmol l(-1)) was minimal. A-cell responses to neutral salts like NaCl, KCl, CaCl2, MgCl2 and C5H14NOCl (pH 6.1-6.5) varied largely in strength. Very low or no responses were observed with chlorides of divalent cations, CaCl2 and MgCl2, and choline chloride (C5H14NOCl), indicating that the ionic composition of the solutions also affected A-cell responses. Neural activity of the C-cell was not influenced by the salt solutions tested.

Antennal sensilla of the ground beetle Bembidion properans Steph. (Coleoptera, Carabidae).

The arrangement of antennal sensilla was studied in female and male ground beetles Bembidion properans Steph. (Coleoptera, Carabidae) using scanning electron microscopy. The filiform antennae, 1.8-1.9 mm in length, consist of the scape, pedicel and nine flagellomeres. In both sexes, three types of sensilla chaetica, two types of sensilla trichodea, six types of sensilla basiconica, one type of sensilla coeloconica and one type of sensilla campaniformia were distinguished. The possible function of the sensilla is discussed and three types of sensilla are considered olfactory, sensilla trichodea type 2 and sensilla basiconica types 1 and 2. Olfactory sensilla form dorsal and/or ventral sensillar fields on the flagellomeres and occur sparsely or not at all outside these areas. No sexual differences in the types, number and distribution of antennal sensilla were found.