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

Cellular reactions to long-term volatile organic compound (VOC) exposures

Investigations of cellular processes initiated by volatile organic compounds (VOCs) are limited when modelling realistic long-term exposure scenarios at low concentrations. Exposure to indoor VOCs is associated with a range of adverse effects, but data on molecular changes at regulatory threshold limits are lacking. Activity analysis of VOC in vitro can be a valuable complement to inhalation toxicological evaluations. We developed an exposure platform that generates a stable VOC atmosphere and allows the exposure of cells for longer periods. Using formaldehyde as a model analyte, air-liquid interface cultured A549 lung epithelial cells were exposed to critical concentrations of 0.1 and 0.5 ppm for 3 days. Owing to the lack of known exposure biomarkers, we applied a genome-wide transcriptional analysis to investigate cellular responses at these sublethal concentrations. We demonstrate a minor overlap of differentially expressed transcripts for both treatment concentrations, which can be further analyzed for their use as exposure biomarkers. Moreover, distinct expression patterns emerge for 0.1 and 0.5 ppm formaldehyde exposure, which is reflected in significant enrichment of distinct biological processes. More specifically, metabolism of specific compound classes, lipid biosynthesis and lung-associated functions are affected by lower exposure levels and processes affecting proliferation and apoptosis dominate the higher exposure levels

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

Second trimester inflammatory and metabolic markers in women delivering preterm with and without preeclampsia.

ObjectiveInflammatory and metabolic pathways are implicated in preterm birth and preeclampsia. However, studies rarely compare second trimester inflammatory and metabolic markers between women who deliver preterm with and without preeclampsia.Study designA sample of 129 women (43 with preeclampsia) with preterm delivery was obtained from an existing population-based birth cohort. Banked second trimester serum samples were assayed for 267 inflammatory and metabolic markers. Backwards-stepwise logistic regression models were used to calculate odds ratios.ResultsHigher 5-α-pregnan-3β,20α-diol disulfate, and lower 1-linoleoylglycerophosphoethanolamine and octadecanedioate, predicted increased odds of preeclampsia.ConclusionsAmong women with preterm births, those who developed preeclampsia differed with respect metabolic markers. These findings point to potential etiologic underpinnings for preeclampsia as a precursor to preterm birth

Neutron captue prompt gamma-ray activation analysis at the NIST Cold Neutron Research Facility

An instrument for neutron capture prompt gamma-ray activation analysis (PGAA) has been constructed as part of the Cold Neutron Research Facility at the 20 MW National Institute of Standards and Technology Research Reactor. The neutron fluence rate (thermal equivalent) is 1.5·10 8 n ·cm −2 ·s −1 , with negligible fast neutrons and gamma-rays. With compact geometry and hydrogen-free construction, the sensitivity is sevenfold better than an existing thermal instrument. Hydrogen background is thirtyfold lower.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/43114/1/10967_2005_Article_BF02035470.pd

River histories : A thematic review

Peer reviewe

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

Pre-exenterative chemotherapy, a novel therapeutic approach for patients with persistent or recurrent cervical cancer

BACKGROUND: Most cervical cancer patients with pelvic recurrent or persistent disease are not candidates for exenteration, therefore, they only receive palliative chemotherapy. Here we report the results of a novel treatment modality for these patients pre-exenterative chemotherapy- under the rational that the shrinking of the pelvic tumor would allow its resection. METHODS: Patients with recurrent or persistent disease and no evidence of systemic disease, considered not be candidates for pelvic exenteration because of the extent of pelvic tumor, received 3-courses of platinum-based chemotherapy. Response was evaluated by CT scan and bimanual pelvic examination; however the decision to perform exenteration relied on the physical findings. Toxicity to chemotherapy was evaluated with standard criteria. Survival was analyzed with the Kaplan-Meier method. RESULTS: Seventeen patients were studied. The median number of chemotherapy courses was 4. There were 9 patients who responded to chemotherapy, evaluated by bimanual examination and underwent pelvic exenteration. Four of them had pathological complete response. Eight patients did not respond and were not subjected to surgery. One patient died due to exenteration complications. At a median follow-up of 11 months, the median survival for the whole group was 11 months, 3 months in the non-operated and 32 months in those subjected to exenteration. CONCLUSION: Pre-exenterative chemotherapy is an alternative for cervical cancer patients that are no candidates for exenteration because of the extent of the pelvic disease. Its place in the management of recurrent disease needs to be investigated in randomized studies, however, its value for offering long-term survival in some of these patients with no other option than palliative care must be stressed