Investigation of aqueous phase dynamics in a uranium stripping unit using radioactive tracer.

Mixer-setters units are widely used in uranium purification processes. For efficient operations of mixer-settler units, it is essential to measure the hydrodynamics parameters of the different phases involved. The residence time distribution (RTD) measurement is commonly used method to estimate the hydrodynamics parameters of process reactors. In the present study, RTD of the aqueous phase was measured in different stages mixer-settler unit (mixers, settlers and mixer-settler units) used for stripping operation using Iodine-131 as a radiotracer. For the RTD measurements, radiotracer was injected as an impulse in aqueous phase feed line and its movement was monitored at different locations in the stripping unit using NaI(Tl) detectors. The mean residence times (MRTs) of the aqueous phase were estimated from measured RTD curves. For quantification of the degree of mixing, suitable flow models were proposed based on design and nature of the measured RTD curves and subsequently used for simulation. Based on the results of the RTD study, the mixing of aqueous phase was characterized and design of the stripping unit and its sub-units were validated. The optimum conditions were identified for efficient for the operation of the stripping unit.

Intestinal Phosphorus Absorption in Moderate CKD and Healthy Adults Determined Using a Radioisotopic Tracer.

BACKGROUND: Reducing intestinal phosphorus absorption is a cornerstone in CKD-MBD management. Yet, knowledge gaps include how CKD pathophysiology affects intestinal phosphorus absorption. In vivo rodent studies suggest that intestinal phosphorus absorption remains inappropriately normal in early-moderate CKD, despite declining 1,25-dihydroxyvitamin D (1,25D). We measured intestinal phosphorus absorption in patients with moderate CKD versus healthy adults using a direct radiotracer method. METHODS: Patients with CKD and healthy adults matched for age, sex, and race were enrolled in this 8-day controlled diet study: the first 6 days outpatient and the final 2 days inpatient. Oral and intravenous doses of 33P and serial blood and urine sampling determined intestinal phosphorus absorption during the final 2 days. Secondary outcomes included fasting biochemistries and 24-hour urine phosphorus (uP). RESULTS: In total, n=8 patients with CKD (eGFR=29-55 ml/min per 1.73 m2) and n=8 matched healthy controls completed the study. On a controlled diet, no difference in fractional intestinal phosphorus absorption was detected between patients with CKD and healthy adults (0.69 versus 0.62, respectively; P=0.52), and this was similar for 24-hour uP (884 versus 935 mg/d, respectively; P=0.70). Fractional intestinal phosphorus absorption was not significantly related to 24-hour uP. Patients with CKD had higher serum intact PTH and intact FGF23 and lower 1,25D. The relationship between 1,25D and fractional intestinal phosphorus absorption was not statistically significant. CONCLUSIONS: Intestinal phosphorus absorption with typical dietary intake did not differ in patients with moderate CKD compared with controls, despite lower serum 1,25D levels. In this setting, a relationship between 24-hour uP and fractional or absolute intestinal absorption was not evident. Further investigation is needed to determine what factors influence intestinal phosphorus absorption in CKD and the apparent lack of compensation by the intestine to limit phosphorus absorption in the face of declining kidney function and reduced 1,25D. Whether this is evident across a range of dietary phosphorus intakes, as well as CKD severity, also needs to be determined. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Phosphorus Absorption in Healthy Adults and in Patients with Moderate Chronic Kidney Disease, NCT03108222.

Comparison of Dual-Tracer PET and CT Features to Conventional Risk Categories in Assessing Response to 177Lu-PSMA-617 Therapy for Metastatic Prostate Adenocarcinoma with Urinary Bladder Involvement.

The present communication details the imaging characteristics, peculiarities, and response to 177Lu-labeled prostate-specific membrane antigen (PSMA)-617-targeted radioligand therapy (PRLT) in accordance with Gleason score and use of dual-tracer PET (68Ga-PSMA-11 and 18F-FDG) in patients with urinary bladder invasion or metastasis by prostate cancer, including the prognostic value of 18F-FDG PET in predicting response to treatment. The CT attenuation units (Hounsfield units) correlated with the prostate primary in the case of direct tumor extension from the prostate, whereas in hematogenous metastatic seeding the Hounsfield units were lower than in the primary prostatic tumor. A favorable outcome to 177Lu-PSMA-617 PRLT was observed in patients with low or no baseline 18F-FDG uptake despite a high Gleason score and a high-risk National Comprehensive Cancer Network prognostic category and did not correlate with the latter alone, whereas a high SUVmax on 18F-FDG PET/CT was associated with an adverse outcome. These findings suggest a promising role for 18F-FDG PET/CT in predicting therapeutic outcomes more confidently, and hence the concept of dual-tracer PET appears to hold good in prostate adenocarcinoma theranostics.

PET and SPECT imaging of the brain: a review on the current status of nuclear medicine in Japan.

Radiolabeled tracers allow visualization of not only perfusion, but receptors, function, and metabolism as well. Although spatial resolution is lower than that of computed tomography and magnetic resonance imaging, positron emission tomography (PET) and single photon emission computed tomography (SPECT) have great potential for target-specific imaging. In this review, we discuss several SPECT and PET tracers used in brain imaging, specifically focusing on tracers currently available, or developed, in Japan. Several important and sophisticated methods exist for analysis of brain PET and SPECT images. Two of them, quantitative cerebral blood flow measurement and voxel-based statistical analysis are discussed in this review. The former method, which employs acetazolamide loading, is useful for evaluation of the brain perfusion reserve for ischemic brain diseases. The latter is useful in diagnosing dementing diseases. Additionally, great strides have been made in the development of the technology used in the scanners. New SPECT systems based on cadmium-zinc-telluride, PET/MRI, and semiconductor PET/CT may provide higher spatial resolution with an acquisition time shorter than ever before. Such developments of both tracers and scanners can be integrated for unprecedented imagery of the brain, providing valuable insight into underlying causes of some fatal brain disorders.

Multiple retrograde tracing methods compatible with 3DISCO clearing.

Exploring the spatial relationship of various neuron pools in the spinal cord is crucial and difficult due to its complexity. The single-labelling tracing and sectioning were employed in previous studies exploring the distribution of spinal motor neuron pools, which could only delineate one single motor neuron pool in one specimen and could not achieve intact-tissue observation. Here, with combination of neuroanatomy tracing techniques and the optical clearing technique, we developed a multiple retrograde tracing method compatible with 3DISCO clearing. Fluoro-Gold, Fluoro-Ruby, Cholera Toxin Subunit B, Alexa Fluor 488 and 647 Conjugate were injected intramuscularly in hindlimbs of C57BL/6 adults. After labelling, the harvested spinal cords were optically cleared by 3DISCO method and imaged using confocal microscope. There were positive signals of all four tracers and four motor neurons pools targeting injected muscles were labelled. Three-dimension model of four motor neuron pools was successfully reconstructed based on tomography images showing the spatial relationship of different neuron pools. In conclusion, using this method, we first delineated the spatial relationship of four different motor neuron pools targeting four skeletal muscles in one spinal cord at the same time, which provide a holistic view of motor neuron pools in the spinal cord.

Monitoring the Response of PD-L1 Expression to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Nonsmall-Cell Lung Cancer Xenografts by Immuno-PET Imaging.

Accumulating evidence has suggested that the tumor microenvironment of nonsmall-cell lung cancer (NSCLC) may be impacted by chemotherapy, radiotherapy, or epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). PD-L1 is an important biomarker in the tumor microenvironment that can predict patient response to immunotherapies. Therefore, it is highly desirable to achieve a real-time, noninvasive assessment of PD-L1 expression, which can provide critical information for recruiting patients as well as monitoring therapeutic efficacy. We herein studied the EGFR-TKI-induced effects on PD-L1 levels in NSCLC tumor models using immuno-PET imaging with 89Zr-Df-KN035, an imaging tracer previously established by our group. A549 human NSCLC xenografts were established in BALB/c nude mice and treated with different doses of an EGFR-TKI gefitinib. PET imaging with 89Zr-Df-KN035 was performed before and after the treatment to evaluate PD-L1 expression, which was further verified by immunohistochemical staining. Our results demonstrate that 89Zr-Df-KN035 can specifically evaluate PD-L1 levels in NSCLC tumor models. Compared to the untreated control, the high dose of gefitinib inhibited tumor growth and lowered the tumor uptake of 89Zr-Df-KN035. In comparison, the low dose of gefitinib did not affect tumor growth, although the extensive tumor necrosis also led to the lower uptake of 89Zr-Df-KN035. In conclusion, our results demonstrate that immuno-PET imaging with 89Zr-Df-KN035 is a promising tool to noninvasively monitor PD-L1 expression in NSCLC treated with EGFR-TKIs and can be used to optimize treatment plans for immunotherapy.

Small Cell Transformation of Metastatic Prostate Adenocarcinoma Diagnosed by Dual-Tracer PET/CT (68Ga-PSMA and 18F-FDG): Potential Clinical Utility in Therapeutic Decision Making and Treatment Monitoring.

Transformed small cell carcinoma of the prostate represents a tumor biology distinct from its adenocarcinoma counterpart, and penile metastasis from prostate cancer is a rare phenomenon. Biologic heterogeneity among metastatic lesions in a patient with prostatic adenocarcinoma with SCPCa transformation is presented here. The case report shows the significance of using dual-tracer PET/CT with 68Ga-prostate-specific membrane antigen and 18F-FDG in diagnosing small cell carcinoma of prostate transformation in certain lesions, thereby guiding therapeutic strategies. Furthermore, the value of sequential dual-tracer PET/CT in assessing overall disease status, theranostics, and response to multimodality therapy is illustrated.

Simultaneous Preclinical Positron Emission Tomography-Magnetic Resonance Imaging Study of Lymphatic Drainage of Chelator-Free 64Cu-Labeled Nanoparticles.

BACKGROUND: Hybrid positron emission tomography (PET)-magnetic resonance imaging (MRI) systems have been taken in use as new clinical diagnostic tools including detection and therapy planning of cancer. To reduce the amount of contrast agents injected in patients while fully benefitting both modalities, dual-modality probes are required. MATERIAL AND METHODS: This study was first aimed at developing a hybrid PET-MRI probe by labeling superparamagnetic iron oxide nanoparticles (SPIONs) with 64Cu using a fast and chelator-free conjugation method, and second, to demonstrate the ability of the agent to target sentinel lymph nodes (SLNs) in vivo using simultaneous PET-MRI imaging. RESULTS: High labeling efficiency of 97% produced within 10-15 min was demonstrated at room temperature. 64Cu-SPIONs were chemically stable in mouse serum for 24 h and after intradermal injection in the hind paw of C57BL/6J mice, demonstrated specific accumulation in the SLN. Simultaneous PET-MRI clearly demonstrated visualization of 64Cu-SPIONs, in dynamic and static imaging sequences up to 24 h after administration. CONCLUSION: The use of a single hybrid probe and simultaneous hybrid imaging provides an efficient, complementary integration of quantitation and is expected to improve preoperative planning and intraoperative guidance of cancer treatments.

Deproteinization assessment using isotopically enriched compounds to trace the coprecipitation of low-molecular-weight selenium species with proteins.

Studies have shown that information related to the presence of low-molecular-weight metabolites is frequently lost after deproteinization of complex matrices, such as blood and plasma, during sample preparation. Therefore, the effect of several deproteinization reagents on low-molecular-weight selenium species has been compared by species-specific isotope labeling. Two isotopically enriched selenium tracers were used to mimic models of small inorganic anionic (77Se-selenite) and organic zwitterionic (76Se-selenomethionine) species. The results presented here show that the use of a methanol-acetonitrile-acetone (1:1:1 v/v/v) mixture provided approximately two times less tracer loss from plasma samples in comparison with the classic procedure using acetonitrile, which may not be optimal as it leads to important losses of low-molecular-weight selenium species. In addition, the possible interactions between selenium tracers and proteins were investigated, revealing that both coprecipitation phenomena and association with proteins were potentially responsible for selenite tracer losses during protein precipitation in blood samples. However, coprecipitation phenomena were found to be fully responsible for losses of both tracers observed in plasma samples and of the selenomethionine tracer in blood samples. This successfully applied strategy is anticipated to be useful for more extensive future studies in selenometabolomics.

Simultaneous in-vivo receptor occupancy assays for serotonin 1A, 2A, and dopamine 2 receptors with the use of non-radiolabelled tracers: Proposed method in screening antipsychotics.

INTRODUCTION: Conventionally, receptor occupancy assays employ radiolabelled tracer. However, recent advances with non-radiolabelled tracers brought a revolution in target engagement assays. Non-radiolabelled tracer based receptor occupancy uses LC-MS/MS based quantification. It offers simultaneous quantification of more than one tracer; thus, provides the feasibility of evaluating multiple targets in a single animal. In the present study, we demonstrated simultaneous measurement of serotonin 1A, serotonin 2A, and dopamine 2 receptor occupancy using non-radiolabelled tracers in rats. METHOD: Non-radiolabelled WAY-100635 or MDL-100,907 or raclopride were used as tracers for 5-HT1A, 5-HT2A, and D2 receptors, respectively. In-vivo brain distribution of these tracers was measured after administration as individual or as a mixture of tracers (cocktail tracer). Similarly, in-vitro brain free fractions were evaluated with the single and cocktail tracer in brain homogenates. The mass spectrometer was used for simultaneous quantification of tracers in both in-vivo and in-vitro samples. A ratio method was employed for calculation of receptor occupancy after single and cocktail tracer administration. Pindolol, olanzapine, and ziprasidone were used as tool compounds for demonstrating receptor occupancy at 5-HT1A, 5-HT2A, and D2 receptors. RESULT: In optimization studies, regional distribution and concentration ratios (specific to non-specific) of these tracers were unaltered with individual and cocktail tracer. Non-significant variability was observed in brain free fraction of tracers' indicating the minimal binding interactions in this tracer combination. The half-maximal effective dose (ED50) for pindolol (5-HT1A 1.37 & 2.42mg/kg, i.v.), olanzapine (5-HT2A 1.37 & 2.12 and D2 1.90 & 2.72mg/kg, p.o.), and ziprasidone (5-HT1A 10.92 & 9.57; 5-HT2A 0.03 & 0.04 and D2 0.11 & 0.08mg/kg, i.v.) were comparable with individual or cocktail tracer. DISCUSSION: The present study demonstrated the utility of non-radiolabelled tracers in simultaneous measurement of multiple target engagement. Use of this method will minimize the time, in addition to the cost in translational research.

Methane production from coal by a single methanogen.

Coal-bed methane is one of the largest unconventional natural gas resources. Although microbial activity may greatly contribute to coal-bed methane formation, it is unclear whether the complex aromatic organic compounds present in coal can be used for methanogenesis. We show that deep subsurface-derived Methermicoccus methanogens can produce methane from more than 30 types of methoxylated aromatic compounds (MACs) as well as from coals containing MACs. In contrast to known methanogenesis pathways involving one- and two-carbon compounds, this "methoxydotrophic" mode of methanogenesis couples O-demethylation, CO2 reduction, and possibly acetyl-coenzyme A metabolism. Because MACs derived from lignin may occur widely in subsurface sediments, methoxydotrophic methanogenesis would play an important role in the formation of natural gas not limited to coal-bed methane and in the global carbon cycle.

Imaging in-vivo tau pathology in Alzheimer's disease with THK5317 PET in a multimodal paradigm.

PURPOSE: The aim of this study was to explore the cerebral distribution of the tau-specific PET tracer [(18)F]THK5317 (also known as (S)-[(18)F]THK5117) retention in different stages of Alzheimer's disease; and study any associations with markers of hypometabolism and amyloid-beta deposition. METHODS: Thirty-three individuals were enrolled, including nine patients with Alzheimer's disease dementia, thirteen with mild cognitive impairment (MCI), two with non-Alzheimer's disease dementia, and nine healthy controls (five young and four elderly). In a multi-tracer PET design [(18)F]THK5317, [(11)C] Pittsburgh compound B ([(11)C]PIB), and [(18)F]FDG were used to assess tau pathology, amyloid-beta deposition and cerebral glucose metabolism, respectively. The MCI patients were further divided into MCI [(11)C]PIB-positive (n = 11) and MCI [(11)C]PIB-negative (n = 2) groups. RESULTS: Test-retest variability for [(18)F]THK5317-PET was very low (1.17-3.81 %), as shown by retesting five patients. The patients with prodromal (MCI [(11)C]PIB-positive) and dementia-stage Alzheimer's disease had significantly higher [(18)F]THK5317 retention than healthy controls (p = 0.002 and p = 0.001, respectively) in areas exceeding limbic regions, and their discrimination from this control group (using the area under the curve) was >98 %. Focal negative correlations between [(18)F]THK5317 retention and [(18)F]FDG uptake were observed mainly in the frontal cortex, and focal positive correlations were found between [(18)F]THK5317 and [(11)C]PIB retentions isocortically. One patient with corticobasal degeneration syndrome and one with progressive supranuclear palsy showed no [(11)C]PIB but high [(18)F]THK5317 retentions with a different regional distribution from that in Alzheimer's disease patients. CONCLUSIONS: The tau-specific PET tracer [(18)F]THK5317 images in vivo the expected regional distribution of tau pathology. This distribution contrasts with the different patterns of hypometabolism and amyloid-beta deposition.

Radiosynthesis and in Vivo Evaluation of Neuropeptide Y5 Receptor (NPY5R) PET Tracers.

Neuropeptide Y receptor type 5 (NPY5R) is a G-protein coupled receptor (GPCR) that belongs to the subfamily of neuropeptide receptors (NPYR) that mediate the action of endogenous neuropeptide Y (NPY). Animal models and preclinical studies indicate a role for NPY5R in the pathophysiology of depression, anxiety, and obesity and as a target of potential therapeutic drugs. To better understand the pathophysiological involvement of NPY5R, and to measure target occupancy by potential therapeutic drugs, it would be advantageous to measure NPY5R binding in vivo by positron emission tomography (PET). Four potent and selective NPY5R antagonists were radiolabeled via nucleophilic aromatic substitution reactions with [(18)F]fluoride. Of the four radioligands investigated, PET studies in anesthetized baboons showed that [(18)F]LuAE00654 ([(18)F]N-[trans-4-({[4-(2-fluoropyridin-3-yl)thiazol-2-yl]amino}methyl)cyclohexyl]propane-2-sulfonamide) penetrates blood brain barrier (BBB) and a small amount is retained in the brain. Slow metabolism of [(18)F]LuAE00654 was observed in baboon plasma. Blocking studies with a specific NPY5R antagonist demonstrated up to 60% displacement of radioactivity in striatum, the brain region with highest NPY5R binding. Our studies suggest that [(18)F]LuAE00654 can be a potential PET radiotracer for the quantification and occupancy studies of NPY5R drug candidates.

64Cu antibody-targeting of the T-cell receptor and subsequent internalization enables in vivo tracking of lymphocytes by PET.

T cells are key players in inflammation, autoimmune diseases, and immunotherapy. Thus, holistic and noninvasive in vivo characterizations of the temporal distribution and homing dynamics of lymphocytes in mammals are of special interest. Herein, we show that PET-based T-cell labeling facilitates quantitative, highly sensitive, and holistic monitoring of T-cell homing patterns in vivo. We developed a new T-cell receptor (TCR)-specific labeling approach for the intracellular labeling of mouse T cells. We found that continuous TCR plasma membrane turnover and the endocytosis of the specific (64)Cu-monoclonal antibody (mAb)-TCR complex enables a stable labeling of T cells. The TCR-mAb complex was internalized within 24 h, whereas antigen recognition was not impaired. Harmful effects of the label on the viability, DNA-damage and apoptosis-necrosis induction, could be minimized while yielding a high contrast in in vivo PET images. We were able to follow and quantify the specific homing of systemically applied (64)Cu-labeled chicken ovalbumin (cOVA)-TCR transgenic T cells into the pulmonary and perithymic lymph nodes (LNs) of mice with cOVA-induced airway delayed-type hypersensitivity reaction (DTHR) but not into pulmonary and perithymic LNs of naïve control mice or mice diseased from turkey or pheasant OVA-induced DTHR. Our protocol provides consequent advancements in the detection of small accumulations of immune cells in single LNs and specific homing to the sites of inflammation by PET using the internalization of TCR-specific mAbs as a specific label of T cells. Thus, our labeling approach is applicable to other cells with constant membrane receptor turnover.

A tracer bolus method for investigating glutamine kinetics in humans.

Glutamine transport between tissues is important for the outcome of critically ill patients. Investigation of glutamine kinetics is, therefore, necessary to understand glutamine metabolism in these patients in order to improve future intervention studies. Endogenous glutamine production can be measured by continuous infusion of a glutamine tracer, which necessitates a minimum measurement time period. In order to reduce this problem, we used and validated a tracer bolus injection method. Furthermore, this method was used to measure the glutamine production in healthy volunteers in the post-absorptive state, with extra alanine and with glutamine supplementation and parenteral nutrition. Healthy volunteers received a bolus injection of [1-13C] glutamine, and blood was collected from the radial artery to measure tracer enrichment over 90 minutes. Endogenous rate of appearance (endoRa) of glutamine was calculated from the enrichment decay curve and corrected for the extra glutamine supplementation. The glutamine endoRa of healthy volunteers was 6.1±0.9 µmol/kg/min in the post-absorptive state, 6.9±1.0 µmol/kg/min with extra alanyl-glutamine (p = 0.29 versus control), 6.1±0.4 µmol/kg/min with extra alanine only (p = 0.32 versus control), and 7.5±0.9 µmol/kg/min with extra alanyl-glutamine and parenteral nutrition (p = 0.049 versus control). In conclusion, a tracer bolus injection method to measure glutamine endoRa showed good reproducibility and small variation at baseline as well as during parenteral nutrition. Additionally, we showed that parenteral nutrition including alanyl-glutamine increased glutamine endoRa in healthy volunteers, which was not attributable to the alanine part of the dipeptide.

The production of Neptunium-236g.

Radiochemical analysis of (237)Np is important in a number of fields, such as nuclear forensics, environmental analysis and measurements throughout the nuclear fuel cycle. However analysis is complicated by the lack of a stable isotope of neptunium. Although various tracers have been used, including (235)Np, (239)Np and even (236)Pu, none are entirely satisfactory. However, (236g)Np would be a better candidate for a neptunium yield tracer, as its long half-life means that it is useable as both a radiometric and mass spectrometric measurements. This radionuclide is notoriously difficult to prepare, and limited in scope. In this paper, we examine the options for the production of (236g)Np, based on work carried out at NPL since 2011. However, this work was primarily aimed at the production of (236)Pu, and not (236g)Np and therefore the rate of production are based on the levels of (236)Pu generated in the irradiation of (i) (238)U with protons, (ii) (235)U with deuterons, (iii) (236)U with protons and (iv) (236)U with deuterons. The derivation of a well-defined cross section is complicated by the relevant paucity of information on the variation of the (236m)Np:(236g)Np production ratio with incident particle energy. Furthermore, information on the purity of (236g)Np so produced is similarly sparse. Accordingly, the existing data is assessed and a plan for future work is presented.

Radon as a natural tracer for gas transport within uranium waste rock piles.

Acid mine drainage (AMD) has been identified as the main cause for outflow of acid water and radioactive/non-radioactive contaminants. AMD encompasses pyrites oxidation when water and oxygen are available. AMD was identified in uranium waste rock piles (WRPs) of Indústrias Nucleares do Brasil-Caldas facility (Brazilian uranium mine), resulting in high costs for water treatment. AMD reduction is the main challenge, and scientific investigation has been conducted to understand oxygen and water transportation within WRPs, where 222Rn is used as natural tracer for oxygen transportation. The study consists of soil radon gas mapping in the top layer of WRP4 using active soil gas pumping, radon adsorption in active charcoal and 222Rn determination using high-resolution gamma-ray spectrometry. A sampling network of 71 points was built where samples were collected at a depth of 40 cm. Soil radon gas concentration ranged from 33.7 to 1484.2 kBq m(-3) with mean concentration of 320.7±263.3 kBq m(-3).

Turnover of Se in adequately fed chickens using Se-75 as a tracer.

Inorganic selenium (Se) in the form of selenite is applied to livestock to avoid Se deficiency. Selenite is, however, an artificial Se source in diets of unsupplemented chickens. It is therefore hypothesized that organic Se sources, such as Se-enriched yeast and wheat, could be a more suitable Se supply in animal nutrition, although information on the transition of Se from organic Se sources in fast-growing chickens is scarce. In this work, chickens were fed a low Se diet (0.27 ± 0.01 mg Se/kg, Se-enriched yeast) until 20 days of age, after which the Se concentration was increased to maximum concentration allowed by the poultry industry in Europe (0.5 p.p.m. Se). At the same time, a daily contribution of carrier-free (75)Se tracer from labelled wheat was administered from day 20 to 27. The chickens showed S and Se homeostasis, as the concentration of S and Se in liver, blood or kidney remained about constant, and steady state of S and Se in the other organs was reached 1 day after the diet shift. The uptake of (75)Se was readily seen in all organs. After 1 week, the depuration of the (75)Se tracer was followed, and biological half-lives and retention in individual organs were determined. The shortest biological half-lives were observed in major metabolic organs, the liver, kidney and pancreas with half-lives close to 4 days. There was a significant (p < 0.05) uptake in lung, brain and muscle that reached steady state when the administration of (75)Se was terminated. The half-life of (75)Se in heart was 9 days and 7 days in blood. The longest half-lives were observed in muscle (12 days), brain and lungs (13 days). All half-lives were shorter than in Se deplete animals.

A class of compartmental models for long-distance tracer transport in plants.

Studies of long-distance tracer transport in plants result in spatio-temporal data sets. Compartmental tracer transport models can be used to quantitatively characterize or compare such data sets derived from different experiments. Depending on the specific experimental situation it might be necessary to apply different models. Here, we present a general class of compartmental tracer transport models which allows a systematic comparison of different models regarding the quality of fitting to the experimental data. This model class is defined by a system of partial differential equations (PDEs) for an arbitrary number of parallel compartments with individual transport velocities and numerous lateral exchange connections. A large number of model instances with adjustable complexity can be derived from this model class by permitting only certain model parameters such as flux velocities or exchange rates between compartments to be non-zero. Since some of these models are either inconsistent or redundant we designed a model filter using combinatory rules in order to keep only valid and unique models. A numerical solver for the PDEs was implemented using finite volumes and a weighted essentially non-oscillatory (WENO) scheme. Several candidate models were fitted to experimental data using a Monte Carlo multi-start strategy to approximate the global optimum within a certain parameter space. Analysis of exemplary tracer transport experiments on sugar beet, radish and maize root resulted in different best models depending on the respective data and the required fit quality.

Tracer level radiochemistry to clinical dose preparation of (177)Lu-labeled cyclic RGD peptide dimer.

AIM: Integrin αvß3 plays a significant role in angiogenesis during tumor growth and metastasis, and is a receptor for the extracellular matrix proteins with the exposed arginine(R)-glycine(G)-aspartic acid(D) tripeptide sequence. The over-expression of integrin αvß3 during tumor growth and metastasis presents an interesting molecular target for both early detection and treatment of rapidly growing solid tumors. Considering the advantages of (177)Lu for targeted radiotherapy and enhanced tumor targeting capability of cyclic RGD peptide dimer, an attempt has been made to optimize the protocol for the preparation of clinical dose of (177)Lu labeled DOTA-E[c(RGDfK)]2 (E=Glutamic acid, f=phenyl alanine, K=lysine) as a potential agent for targeted tumor therapy. METHODS: (177)Lu was produced by thermal neutron bombardment on enriched Lu2O3 (82% in (176)Lu) target at a flux of 1 × 10(14) n/cm(2).s for 21 d. Therapeutic dose of (177)Lu-DOTA-E[c(RGDfK)]2 (7.4GBq) was prepared by adding the aqueous solution of the ligand and (177)LuCl3 to 0.1M NH4OAC buffer containing gentisic acid and incubating the reaction mixture at 90°C for 30 min. The yield and radiochemical purity of the complex was determined by HPLC technique. Parameters, such as, ligand-to-metal ratio, pH of the reaction mixture, incubation time and temperature were varied using tracer quantity of (177)Lu (37 MBq) in order to arrive at the optimized protocol for the preparation of clinical dose. Biological behavior of the radiotracer prepared was studied in C57/BL6 mice bearing melanoma tumors. RESULTS: (177)Lu was produced with a specific activity of 950 ± 50 GBq/mg (25.7 ± 1.4 Ci/mg) and radionuclidic purity of 99.98%. A careful optimization of several parameters showed that (177)Lu-DOTA-E[c(RGDfK)]2 could be prepared with adequately high radiochemical purity using a ligand-to-metal ratio ~2. Based on these studies therapeutic dose of the agent with 7.4 GBq of (177)Lu was formulated in ~63 GBq/µM specific activity with high yield (98.2 ± 0.7%), radiochemical purity and in vitro stability. Biodistribution studies carried out in C57/BL6 mice bearing melanoma tumors revealed specific accumulation of the radiolabeled conjugate in tumor (3.80 ± 0.55% ID/g at 30 min p.i.) with high tumor to blood and tumor to muscle ratios. However, the uptake of the radiotracer in the tumor was found to be reduced to 1.51 ± 0.32 %ID/g at 72 h p.i. CONCLUSIONS: The present work successfully demonstrates the formulation of an optimized protocol for the preparation of (177)Lu labeled DOTA-E[c(RGDfK)]2 for PRRT applications using (177)Lu produced by direct neutron activation in a medium flux research reactor.