Cyclotron production and cyclometallation chemistry of 192Ir

Introduction To explore new questions and techniques in nuclear medicine, new isotopes with novel chemical and nuclear properties must be developed. We are interested in the small cyclotron production of new radiometals for the development of new radiopharmaceuticals (RX). In an example of RX multifunctionality, Luminescence Cell Imaging (LCI) has been combined with radio-isotopes to allow compounds that can be imaged with both optical microscopy and nuclear techniques [1]. Within this field, iridium cy-clometalates have good potential with excellent photophysical properties [2]. As well, low specific activity iridium-192 has found use in brachy-therapy as a high-intensity beta emitter [3]. Despite this, iridium radioisotopes have yet to be applied to cyclometalation chemistry, or a radiochemical isolation method developed for carrier free production on a medical cyclotron. Our goal is to demonstrate the feasibility of the production and isolation of radio-iridium, and its application to cyclometalate chemistry as a potentially interesting tool for nuclear medicine research. Materials and Methods Following literature precedent [4], natural osmium was electroplated onto a silver disc from basic media containing osmium tetroxide and sulphamic acid. The thin deposits obtained (15–20 mg cm−2) were weighed and characterized with scanning electron microscopy. Targets were irradiated using the TRIUMF TR13 cyclotron, delivering 12.5 MeV protons to the target disc. Initial bombardments were per-formed at 5 μA; gamma spectra of the targets were collected 24 hours after end of bombardment. The irradiated material was oxidized, dissolved from the target backing, and separated via anion exchange. In parallel to the isotope production work, non-radioactive iridium was used to define a chemical procedure suitable for the synthesis of model iridium cyclometalate compounds given low concentrations of radioiridium. These experiments will be performed with radioactive iridium in the next step of the research project. Results and Conclusion Proton bombardment of natural osmium yielded a range of iridium isotopes, with characteristic spectral lines corresponding to 186-190Ir, and 192Ir; no other characteristic radiation was observed. The EOB activity of each isotope was then used in thin target calculations to approximate their (p,n) cross section. Preliminary cross section measurements of the 192Os(p,n)192Ir reaction (53 ± 13 mb @ 12.5 MeV) confirm published data (52.3 ± 5.7 mb @ 12.2 MeV) [6], and provide as-yet unpublished data on the lower mass number isotopes. The progress of radioactive iridium through the radiochemical separation was tracked with a dose calibrator; the osmium complex formed was brightly coloured and could be seen retained on the column. The overall efficiency of the process is estimated at 80 %. Radioactive cyclometallation chemistry is currently under-way. The production and isolation of a range of iridium isotopes in a chemically useful form was demonstrated, and is ready to be applied to a cyclometalate model compound. Future work will investigate the production of 192Ir from enriched 192Os

Apple fruit periderms (russeting) induced by wounding or by moisture have the same histologies, chemistries and gene expressions

Russeting is a cosmetic defect of some fruit skins. Russeting (botanically: induction of periderm formation) can result from various environmental factors including wounding and surface moisture. The objective was to compare periderms resulting from wounding with those from exposure to moisture in developing apple fruit. Wounding or moisture exposure both resulted in cuticular microcracking. Cross-sections revealed suberized hypodermal cell walls by 4 d, and the start of periderm formation by 8 d after wounding or moisture treatment. The expression of selected target genes was similar in wound and moisture induced periderms. Transcription factors involved in the regulation of suberin (MYB93) and lignin (MYB42) synthesis, genes involved in the synthesis (CYP86B1) and the transport (ABCG20) of suberin monomers and two uncharacterized transcription factors (NAC038 and NAC058) were all upregulated in induced periderm samples. Genes involved in cutin (GPAT6, SHN3) and wax synthesis (KCS10, WSD1, CER6) and transport of cutin monomers and wax components (ABCG11) were all downregulated. Levels of typical suberin monomers (ω-hydroxy-C20, -C22 and -C24 acids) and total suberin were high in the periderms, but low in the cuticle. Periderms were induced only when wounding occurred during early fruit development (32 and 66 days after full bloom (DAFB)) but not later (93 DAFB). Wound and moisture induced periderms are very similar morphologically, histologically, compositionally and molecularly

Production of radiometals in a liquid target

Introduction Access to radiometals suitable for labeling novel molecular imaging agents requires that they be routinely available and inexpensive to obtain. Proximity to a cyclotron center outfitted with solid target hardware, or to an isotope generator for a radiometal of interest is necessary, both of which can be significant hurdles in availability of less common isotopes. Herein, we describe the production of 44Sc, 68Ga, 89Zr, 86Y and 94mTc in a solution target which allows for the production of various radiometallic isotopes, enabling rapid isotope-biomolecule pairing optimization for tracer development. Work on solution targets has also been performed by other groups [e.g. 1, 2]. Material and Methods Solutions containing a high concentration of natural-abundance zinc nitrate, yttrium nitrate, calcium nitrate [3], strontium nitrate or ammonium heptamolybdate [4] were irradiated on a 13 MeV cyclotron using a standard liquid target. Some of the solutions contained additional hydrogen peroxide or nitric acid to improve solubility and reduce pressure rise in the target during irradiation. Yields calculated using theoretical cross sections (EMPIRE [5]) were compared to the measured yields. In addition, we tested a thermo-syphon target design for the production of 44Sc. Chemical separation of the product from the target material was carried out on a remote apparatus modeled after that of Siikanen [6]. Results and Conclusion The proposed approach enabled the production of quantities sufficient for chemical or biological studies for all metals discussed. In the case of 68Ga, activity up to 480 ± 22 MBq was obtained from a one hour run with a beam current of 7 µA, potentially enabling larger scale clinical production. Considering all reactions, the ratio of theoretical saturation yields to experimental yields ranges from 0.8 for 94mTc to 4.4 for 44Sc. The thermo-syphon target exhibited an increase of current on the target by a factor of 2.5 and an increase in yield by a factor of five for the production of 44Sc. Separation methods were developed for all isotopes and separation efficiency ranges from 71 ± 1 % for 94mTc to 99 ± 4 % for 86Y. 44Sc, 68Ga, and 86Y were successfully used in labeling studies with a model 1,4,7,10-tetrazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelate, while 89Zr coordination behavior was tested using desferrioxamine-alkyne (DFO-alkyne). In summary, we present a promising new method to produce a suite of radiometals in a liquid target. Future work will continue to expand the list of radiometals and to apply this approach to the development of various peptide, protein and antibody radiotracers

Russeting in apple is initiated after exposure to moisture ends: Molecular and biochemical evidence

Exposure of the fruit surface to moisture during early development is causal in russeting of apple (Malus × domestica Borkh.). Moisture exposure results in formation of microcracks and de-creased cuticle thickness. Periderm differentiation begins in the hypodermis, but only after discon-tinuation of moisture exposure. Expressions of selected genes involved in cutin, wax and suberin synthesis were quantified, as were the wax, cutin and suberin compositions. Experiments were con-ducted in two phases. In Phase I (31 days after full bloom) the fruit surface was exposed to moisture for 6 or 12 d. Phase II was after moisture exposure had been discontinued. Unexposed areas on the same fruit served as unexposed controls. During Phase I, cutin and wax synthesis genes were down-regulated only in the moisture-exposed patches. During Phase II, suberin synthesis genes were up-regulated only in the moisture-exposed patches. The expressions of cutin and wax genes in the moisture-exposed patches increased slightly during Phase II, but the levels of expression were much lower than in the control patches. Amounts and compositions of cutin, wax and suberin were con-sistent with the gene expressions. Thus, moisture-induced russet is a two-step process: moisture exposure reduces cutin and wax synthesis, moisture removal triggers suberin synthesis. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Bioimpedance cardiography in pregnancy: A longitudinal cohort study on hemodynamic pattern and outcome

Background: Pregnancy associated cardiovascular pathologies have a significant impact on outcome for mother and child. Bioimpedance cardiography may provide additional outcome-relevant information early in pregnancy and may also be used as a predictive instrument for pregnancy-associated diseases. Methods: We performed a prospective longitudinal cohort trial in an outpatient setting and included 242 pregnant women. Cardiac output and concomitant hemodynamic data were recorded from 11th-13th week of gestation every 5th week as well as at two occasions post partum employing bioimpedance cardiography. Results: Cardiac output increased during pregnancy and peaked early in the third trimester. A higher heart rate and a decreased systemic vascular resistance were accountable for the observed changes. Women who had a pregnancy-associated disease during a previous pregnancy or developed hypertension or preeclampsia had a significantly increased cardiac output early in pregnancy. Furthermore, an effect of cardiac output on birthweight was found in healthy pregnancies and could be confirmed with multiple linear regression analysis. Conclusions: Cardiovascular adaptation during pregnancy is characterized by distinct pattern described herein. These may be altered in women at risk for preeclampsia or reduced birthweigth. The assessment of cardiac parameters by bioimpedance cardiography could be performed at low costs without additional risks

Emil und die Detektive: Early German sound cinema aesthetic

In 1931 Gerhard Lamprecht directed the film version of Erich Kaestner's popular novel Emil und die Detektive. A hugely successful fil

River histories : A thematic review

Peer reviewe

High power targets for cyclotron production of 99mTc‡

Introduction Technetium-99m, supplied in the form of 99Mo/99mTc generators, is the most widely used radioisotope for nuclear medical imaging. The parent isotope 99Mo is currently produced in nuclear reactors. Recent disruptions in the 99Mo supply chain [1] prompted the development of methods for the direct accelerator-based production of 99mTc. Our approach involves the 100Mo(p,2n)99mTc reaction on isotopically enriched molybdenum using small medical cyclotrons (Ep ≤ 20 MeV), which is a viable method for the production of clinically useful quantities of 99mTc [2]. Multi-Curie production of 99mTc requires a 100Mo target capable of dissipating high beam intensities [3]. We have reported the fabrication of 100Mo targets of both small and large area tar-gets by electrophoretic deposition and subsequent sintering [4]. As part of our efforts to further enhance the performance of molybdenum targets at high beam currents, we have developed a novel target system (initially de-signed for the GE PETtrace cyclotron) based on a pressed and sintered 100Mo plate brazed onto a dispersion-strengthened copper backing. Materials and Methods In the first step, a molybdenum plate is produced similarly to the method described in [5] by compacting approximately 1.5 g of commercially available 100Mo powder using a cylindrical tool of 20 mm diameter. A pressure between 25 kN/cm2 and 250 kN/cm2 is applied by means of a hydraulic press. The pressed molybdenum plate is then sintered in a reducing atmosphere (Ar/2% H2) at 1,700 oC for five hours. The resulting 100Mo plates have about 90–95 % of the molybdenum bulk density. The 100Mo plate is furnace brazed at ~750 oC onto a backing manufactured from a disperse on strengthened copper composite (e.g. Glidcop AL-15) using a high temperature silver-copper brazing filler. This process yields a unique, mechanically and thermally robust target system for high beam power irradiation. Irradiations were performed on the GE PETtrace cyclotrons at LHRI and CPDC with 16.5 MeV protons and beam currents ≥ 100 µA. Targets were visually inspected after a 6 hour, 130 µA bombardment (2.73 kW/cm2, average) and were found fully intact. Up to 4.7 Ci of 99mTc have been produced to date. The saturated production yield remained constant between 2 hour and 6 hour irradiations. Results and Conclusion These results demonstrate that our brazed tar-get assembly can withstand high beam intensities for long irradiations without deterioration. Efforts are currently underway to determine maximum performance parameters

Leopard syndrome

LEOPARD syndrome (LS, OMIM 151100) is a rare multiple congenital anomalies condition, mainly characterized by skin, facial and cardiac anomalies. LEOPARD is an acronym for the major features of this disorder, including multiple Lentigines, ECG conduction abnormalities, Ocular hypertelorism, Pulmonic stenosis, Abnormal genitalia, Retardation of growth, and sensorineural Deafness. About 200 patients have been reported worldwide but the real incidence of LS has not been assessed. Facial dysmorphism includes ocular hypertelorism, palpebral ptosis and low-set ears. Stature is usually below the 25th centile. Cardiac defects, in particular hypertrophic cardiomyopathy mostly involving the left ventricle, and ECG anomalies are common. The lentigines may be congenital, although more frequently manifest by the age of 4–5 years and increase throughout puberty. Additional common features are café-au-lait spots (CLS), chest anomalies, cryptorchidism, delayed puberty, hypotonia, mild developmental delay, sensorineural deafness and learning difficulties. In about 85% of the cases, a heterozygous missense mutation is detected in exons 7, 12 or 13 of the PTPN11 gene. Recently, missense mutations in the RAF1 gene have been found in two out of six PTPN11-negative LS patients. Mutation analysis can be carried out on blood, chorionic villi and amniotic fluid samples. LS is largely overlapping Noonan syndrome and, during childhood, Neurofibromatosis type 1-Noonan syndrome. Diagnostic clues of LS are multiple lentigines and CLS, hypertrophic cardiomyopathy and deafness. Mutation-based differential diagnosis in patients with borderline clinical manifestations is warranted. LS is an autosomal dominant condition, with full penetrance and variable expressivity. If one parent is affected, a 50% recurrence risk is appropriate. LS should be suspected in foetuses with severe cardiac hypertrophy and prenatal DNA test may be performed. Clinical management should address growth and motor development and congenital anomalies, in particular cardiac defects that should be monitored annually. Hypertrophic cardiomyopathy needs careful risk assessment and prophylaxis against sudden death in patients at risk. Hearing should be evaluated annually until adulthood. With the only exception of ventricular hypertrophy, adults with LS do not require special medical care and long-term prognosis is favourable