A phase 1 open label study to assess the human mass balance and metabolite profile of 14C-fosmanogepix, a novel Gwt-1 inhibitor in healthy male participants.

Fosmanogepix [FMGX; active form manogepix (MGX)], a novel antifungal, is currently being studied for the treatment of invasive fungal diseases caused by Candida spp., Aspergillus spp., and other rare molds. This Phase 1, single-dose study used 14C-radiolabeled FMGX to determine the disposition and metabolism of FMGX. Ten healthy male participants were enrolled equally into: oral cohort {FMGX 500 mg oral + 3.1 megabecquerel [MBq, 84.0 microcurie (µCi)] 14C} and intravenous (IV) cohort [FMGX 600 mg IV + 3.4 MBq (93.0 µCi) 14C]. At the end of the sampling period (456 h post-dose), 90.2% of radioactivity administered was recovered (46.4% from urine; 43.8% from feces) in oral cohort (82.3% within 240 h), and 82.4% was recovered (42.5% from urine; 39.9% from feces) in IV cohort (76.2% within 264 h), indicating that FMGX elimination occurs via renal and hepatic routes. Radioactivity transformation pathways (oral and IV) indicated multiple major routes of metabolism of FMGX, mainly via MGX, and included oxidation, oxidative deamination, and conjugation. All except one key human plasma metabolite was observed in toxicity species, but its proportion (<10%) in the human area under the curve plasma samples was not of toxicological concern. No deaths, serious, or severe adverse events (AE) were reported, and there were no AE-related withdrawals. The results of this study indicated extensive metabolism of FMGX, with similar key human plasma metabolites observed in the animal studies. The elimination of FMGX was equally through renal and hepatic routes. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT04804059.

Teeth and alveolar bones as tracers of metals and radionuclides in inhabitants of a uranium region.

Biodosimetry can define risks in inhabitants of areas with potential contaminants, ensuring environmental protection and living conditions due to toxic and radioactive effects. This study aimed to evaluate metals and radionuclides in dental structures and alveolar bones in residents of a uranium area in Paraíba and Pernambuco, Brazil. Eighty-nine specimens were pulverized, fractionated, and chemically prepared for analysis by EDXRF, FAAS, and ICP-MS. Levels of Ca, Cu, Fe, Si, Mn, Ni, Pb, Sr, Ti, V, Zn, K, Mn, Th, and U were investigated. Higher concentrations were measured for Ca, with an average of 272,986.4 mg kg-1. Ni presented in lower concentrations, with an average of 30.4 mg kg-1. For U, concentrations ranged from 1.5 to 145.0 mg kg-1, with more than 27% of the samples above the reference value of 8.1 µg kg-1. For Th, almost 38% of the results were above the limit of 3.5 µg kg-1. In the bone spicules, the contents of U and Th ranged from 45.1 to 1451.2 µg kg-1 and from 7.5 to 78.4 µg kg-1, in this order. The levels of radionuclides were more expressive for the teeth collected in São José do Sabugi, suggesting contamination through food and water consumption. In the bone spicules, the levels of U were up to 179 times higher than the safety limit. The results indicate a possible risk of contamination with probable induced radiobiological effects.

Radioactivity of inert construction and demolition waste from Hong Kong and environmental assessment for marine trial reclamation in Guanghai Bay.

Inert construction and demolition waste from Hong Kong (HK public fills) has been used for marine trial reclamation in the Guanghai Bay (GHWT) of the Chinese Mainland. However, an environmental assessment of HK public fills is necessary due to higher radioactivity in HK soils than typical global levels. Here, radiation dose rate, gamma radionuclides and gross beta of HK public fills were analyzed. The origin information was explored using natural primordial radionuclides as fingerprints. Our data show that radiation dose rate of HK public fills before disposal was 0.14-0.54 (0.33 ± 0.03) µSv/h (n = 16,722 data with 2787 ships) in 2014, which is less than the GHWT background. Monthly detection of 238U, 226Ra, 210Pb, 232Th, 228Th, 40K, and gross beta in HK public fills was conducted on three random ships. Their specific activities were <6.27-155.5, 58.7-98.7, <7.83-238.2,97.9-168.6, 87.1-136.0, 463.1-1,018, and 1047-1658 Bq/kgDW, respectively. These results suggest that the radioactivity levels of HK public fills are essentially the same as the GHWT background. The study assessed potential risks using various indices icluding Raeq (Radium equivalent activity), Hex (External radiation hazard index), Hin (Internal radiation hazard index), Iγ (Gamma index), AUI (Activity utilization index), AUI (Activity utilization index), E (Annual effective dose), AGDE (Annual gonadal dose equivalent), RLI (Representative level index), Din (Indoor air absorbed dose rate), Dout (Outdoor air absorbed dose rate), and ELCR (Excess lifetime cancer risk). The study suggests that HK public fills should be used for the trial reclamation rather than building-house materials. This provides valuable insights for the resource utilization and minimizing environmental pollution of HK public fills. The aim is to offer fundamental technical assistance for future waste resource utilization, ecological protection, and restoration in the Guangdong-Hong Kong-Macao Greater Bay Area.

210Po and 210Pb radioactivity levels in local and imported tobacco used in Palestine and Jordan.

This study aimed to assess the concentrations of 210Po and 210Pb in various tobacco samples from Palestine and Jordan. Cigarette smoking is recognized as a significant contributor to the radiation dose received by individuals, primarily due to the elevated levels of 210Pb and 210Po found in tobacco. The analysis revealed that the average concentrations of 210Po in locally sourced tobacco and cigarette samples in Palestine are 16.8 ± 2.3 mBq/g and 18.5 ± 2.0 mBq/g, with a total average of 17.8 ± 7.4 mBq/g (15.5 mBq/cigarette). Similarly, the average concentrations of 210Pb in these samples are 18.5 ± 2.6 mBq/g and 20.3 ± 2.2 mBq/g, with a total average of 19.6 ± 8.1 mBq/g (17.0 mBq/cigarette). In Jordan, the average concentrations of 210Po in cigarette samples and narghile tobacco are 20.1 ± 2.4 mBq/g and 18.3 ± 4.1 mBq/g, with a total average value of 19.6 ± 9.9 mBq/g (18.0 mBq/cigarette), while the average concentrations of 210Pb are 22.2 ± 2.6 mBq/g and 20.2 ± 4.5 mBq/g, with a total average value of 21.6 ± 10.8 mBq/g (19.9 mBq/cigarette). The annual effective doses resulting from inhalation were calculated for smokers of these samples. The findings revealed that the levels of 210Po and 210Pb radioactivity in certain investigated samples exceeded the results of studies in many countries of the world. The associated effective doses per year from smoking for all brands products in Palestine range from 34.7 µSv/y to 186.5 µSv/y with an average of 109.5 µSv/y, while in Jordan 54.5 µSv/y to 289.1 µSv/y with an average of 130.9 µSv/y.

Residential radon decay products are associated with cough and phlegm in patients with COPD.

Radon decay products attach to particulate matter (referred to as particle radioactivity, PR) has been shown to be potential to promote airway damage after inhalation. In this study, we investigated associations between PR with respiratory symptoms and health-related quality of life (HRQL) in patients with COPD. 141 male patients with COPD, former smokers, completed the St. George's Respiratory Questionnaire (SGRQ) after up to four 1-week seasonal assessments (N=474) of indoor (home) and ambient (central site) particulate matter ≤ 2.5 µm in diameter (PM2.5) and black carbon (BC). Indoor PR was measured as α-activity (radiation) on PM2.5 filter samples. The ratio of indoor/ambient sulfur in PM2.5 (a ventilation surrogate) was used to estimate α-PR from indoor radon decay. SGRQ responses assessed frequent cough, phlegm, shortness of breath, wheeze, and chest attacks in the past 3 months. Multivariable linear regression with generalized estimating equations accounting for repeated measures was used to explore associations, adjusting for potential confounders. Median (IQR) indoor α-PR was 1.22 (0.62) mBq/m3. We found that there were positive associations between α-PR with cough and phlegm. The strongest associations were with estimated α-PR of indoor origin for cough (31.1 % increase/IQR, 95 %CI: 8.8 %, 57.8 %), and was suggestive for phlegm (13.0 % increase/IQR, 95 %CI: -2.5 %, 31.0 %), similar adjusting for indoor BC or PM2.5. α-PR of indoor origin was positively associated with an increase in SGRQ Symptoms score [1.2 units/IQR; 95 %CI: -0.3, 2.6] that did not meet conventional levels of statistical significance. Our results suggested that exposure to indoor radon decay products measured as particle radioactivity, a common indoor exposure, is associated with cough, and suggestively associated with phlegm and worse HRQL symptoms score in patients with COPD.

Efficient Synthesis and HPLC-Based Characterization for Developing Vanadium-48-Labeled Vanadyl Acetylacetonate as a Novel Cancer Radiotracer for PET Imaging.

Bis(acetylacetonato)oxidovanadium(IV) [(VO(acac)2], generally known as vanadyl acetylacetonate, has been shown to be preferentially sequestered in malignant tissue. Vanadium-48 (48V) generated with a compact medical cyclotron has been used to label VO(acac)2 as a potential radiotracer in positron emission tomography (PET) imaging for the detection of cancer, but requires lengthy synthesis. Current literature protocols for the characterization of VO(acac)2 require macroscale quantities of reactants and solvents to identify products by color and to enable crystallization that are not readily adaptable to the needs of radiotracer synthesis. We present an improved method to produce vanadium-48-labeled VO(acac)2, [48V]VO(acac)2, and characterize it using high-performance liquid chromatography (HPLC) with radiation detection in combination with UV detection. The approach is suitable for radiotracer-level quantities of material. These methods are readily applicable for production of [48V]VO(acac)2. Preliminary results of preclinical, small-animal PET studies are presented.

Radioactivity and dose assessment of naturally occurring radionuclides in terrestrial environments and foodstuffs: a review of Bahi district, Tanzania.

In this review, the online searchable research articles were scrutinized for the data presented in line with radioactivity and dose estimates from both terrestrial environments and foodstuffs from Bahi district and other parts of Tanzania. The data on natural gamma ray dose rates from Bahi localities were observed with variations among researchers. The observed ranges of radioactivity concentrations (Bq kg-1) in soil were 226Ra (28.5-57.4), 232Th (38.1-521.3), and 40K (562.9-665.0). Deep closed water wells with installed pumps from Ilindi and Bahi Mission reported radioactivity concentration of 238U 3.08 Bq L-1 and Ilindi swamps reported radioactivity concentrations of 226Ra 15.35 Bq L-1, whereas radioactivity concentrations of 238U in cereals were within the annual tolerable limits of 0.001-0.02 Bq kg-1. The quantity and accessibility of published studies, as well as the diversity of the data, point to the necessity for additional studies to be carried out in order to obtain comprehensive baseline data.

Radiological characterization of the tailings of an abandoned copper mine using a neural network and geostatistical analysis through the Co-Kriging method.

The radiological characterization of soil contaminated with natural radionuclides enables the classification of the area under investigation, the optimization of laboratory measurements, and informed decision-making on potential site remediation. Neural networks (NN) are emerging as a new candidate for performing these tasks as an alternative to conventional geostatistical tools such as Co-Kriging. This study demonstrates the implementation of a NN for estimating radiological values such as ambient dose equivalent (H*(10)), surface activity and activity concentrations of natural radionuclides present in a waste dump of a Cu mine with a high level of natural radionuclides. The results obtained using a NN were compared with those estimated by Co-Kriging. Both models reproduced field measurements equivalently as a function of spatial coordinates. Similarly, the deviations from the reference concentration values obtained in the output layer of the NN were smaller than the deviations obtained from the multiple regression analysis (MRA), as indicated by the results of the root mean square error. Finally, the method validation showed that the estimation of radiological parameters based on their spatial coordinates faithfully reproduced the affected area. The estimation of the activity concentrations was less accurate for both the NN and MRA; however, both methods gave statistically comparable results for activity concentrations obtained by gamma spectrometry (Student's t-test and Fisher's F-test).

Assessment of radioactivity level and associated radiological hazard in fertilizer from Dhaka.

Miners, factory workers, traders, end-users, and foodstuff consumers all run the risk of encountering health hazards derived from the presence of elevated levels of radiation in fertilizers, as these groups often come into direct or indirect contact with fertilizers as well as raw materials throughout various linked processes such as mineral extractions, fertilizer production, agricultural practices. A total of 30 samples of various kinds of fertilizer produced in different factories in Dhaka megacity were analyzed to quantify the concentrations of primordial radionuclides using HPGe detector. Among the analyzed samples, average (range) concentration of 40K was found to be 9920 ± 1091 (8700 ± 957-11,500 ± 1265), 9100 ± 1001 (8600 ± 946-9600 ± 1056), 2565 ± 282 (2540 ± 279-2590 ± 285), and 3560 ± 392 (2620 ± 288-4500 ± 495) Bq/kg in the samples of Muriate of Potash Fertilizer, Sulphate of Potash Fertilizer, Humic Acid Fertilizer, and NPKS Fertilizer, respectively. Elevated concentration of 226Ra was found in Triple Super Phosphate Fertilizer with a mean (range) of 335 ± 37 (290 ± 32-380 ± 42) Bq/kg. The higher activity of 40K can be linked to the greater levels of elemental potassium in phosphate fertilizer. Elevated concentrations of radionuclides may also result from variations in chemical processes as well as the local geology of the mining areas where the raw materials were extracted for fertilizer production. Numerous fertilizer brands surpass prescribed limits for various hazardous parameters, presenting significant health risks to factory workers, farmers, and consumers of agricultural products. This study provides baseline information on the radioactivity of fertilizers, which could be used to develop mitigation methods, establish national fertilizer usage limits, justify regulatory frameworks, and raise public awareness of fertilizer overuse. The findings of the study could potentially help to explore the impact of fertilizer on the food chain.

Investigating radiation profiles and conducting risk assessment for ecological and environmental components on Vaan and Koswari islands in the Tuticorin group of islands, India.

Natural radioactive concentration assessment was conducted on sediment, water, and biota obtained on Vaan and Koswari islands in the Tuticorin group of islands, Tamil Nadu, India. For biotic and abiotic components, radiation profiles such as gross alpha, beta, primordial radionuclide, polonium, and lead analyses were performed. The gross α and ß range from BDL to 15.18 ± 1.7 Bq/kg and 40.43 ± 4.9 Bq/kg to 105.12 ± 11.7 Bq/kg, respectively. Primordial radionuclides were analyzed using Nal(TI)-based scintillator with PC-MCA, and the concentrations ranged from 13.43 ± 3.3 Bq/kg to 30.97 ± 9.6 Bq/kg with a mean of 21.31 ± 2.7 Bq/kg for 238U; for 232Th, the values ranged from 11.09 ± 2.6 Bq/kg to 33.55 ± 9.5 Bq/kg with an average value of 23.89 ± 3.7 Bq/kg; and for 40 K, the values are 93.33 ± 27.3 Bq/kg to 219.91 ± 39.6 Bq/kg with an average value of 148.27 ± 21.7 Bq/kg. The present study values are lesser than the world average values. 210Po and 210Pb concentrations with an average value were determined to be 33.13 Bq/L and 16.56 Bq/L, 47.55 Bq/L and 22.37 Bq/L in the water sample, and 50.437 Bq kg1 and 62.012 Bq kg1, 46.99 Bq/kg and 58.625 Bq/kg in sediments of Vaan island and Koswari island. The concentrations of 210Po and 210Pb of Pogonias cromis were 19.27 ± 1.5 Bq/kg and 8.27 ± 1.01 Bq/kg, Belonidae 28.54 ± 2.4 Bq/kg and 18.32 ± 2.3 Bq/kg, Lepisosteidae 18.68 ± 1.4 Bq/kg and 11.17 ± 1.8 Bq/kg. The committed effective dosage was determined to be 35.74-54.61 µSv/y for 210Po and 25.39-56.25 µSv/y for 210Pb, in which the 210Pb value is lower; however, the 210Po value is higher than the global average value. The annual committed effective dosage as well as the radiological hazard indices were assessed and found to be much below the global average and the recommended limit, respectively. This research provides an extensive analysis of natural background radiation and establishes a baseline report on the radiological profile of biotic and abiotic factors in the Tuticorin group of islands, namely Vaan and Koswari, in Tamil Nadu, India.

The distribution of natural radionuclides 40K, 228Ac, and 226Ra on Romanian Territory: a radiometric study.

To estimate the radiation hazard due to the natural terrestrial radioactivity, 598 samples of soil covering the entire Romanian territory were collected and analyzed for the distribution of natural radionuclides 40K, 228Ac, and 226Ra. The ultra-low background Slanic-Prahova underground laboratory was used to determine the gamma-ray-specific activity of these radioactive isotopes with an uncertainty between 5 and 20%. All these data permitted to establishing a set of 2D maps illustrating the distribution of specific activity of each radionuclide as well as of the resulting air dose rate, all of them illustrating an heterogeneous distribution, increased values being displaced on the western and south-western territory. Mediated over 598 points, these determinations led to a value of annual effective dose of 0.7 ± 0.15 mSv/y and an external hazard index of 0.46 ± 0.1, both attesting to a radioecologically safe environment for human activity.

Characterization of chimeric antigen receptor modified T cells expressing scFv-IL-13Rα2 after radiolabeling with 89Zirconium oxine for PET imaging.

BACKGROUND: Chimeric antigen receptor (CAR) T cell therapy is an exciting cell-based cancer immunotherapy. Unfortunately, CAR-T cell therapy is associated with serious toxicities such as cytokine release syndrome (CRS) and neurotoxicity. The mechanism of these serious adverse events (SAEs) and how homing, distribution and retention of CAR-T cells contribute to toxicities is not fully understood. Enabling in vitro methods to allow meaningful, sensitive in vivo biodistribution studies is needed to better understand CAR-T cell disposition and its relationship to both effectiveness and safety of these products. METHODS: To determine if radiolabelling of CAR-T cells could support positron emission tomography (PET)-based biodistribution studies, we labeled IL-13Rα2 targeting scFv-IL-13Rα2-CAR-T cells (CAR-T cells) with 89Zirconium-oxine (89Zr-oxine) and characterized and compared their product attributes with non-labeled CAR-T cells. The 89Zr-oxine labeling conditions were optimized for incubation time, temperature, and use of serum for labeling. In addition, T cell subtype characterization and product attributes of radiolabeled CAR-T cells were studied to assess their overall quality including cell viability, proliferation, phenotype markers of T-cell activation and exhaustion, cytolytic activity and release of interferon-γ upon co-culture with IL-13Rα2 expressing glioma cells. RESULTS: We observed that radiolabeling of CAR-T cells with 89Zr-oxine is quick, efficient, and radioactivity is retained in the cells for at least 8 days with minimal loss. Also, viability of radiolabeled CAR-T cells and subtypes such as CD4 + , CD8 + and scFV-IL-13Rα2 transgene positive T cell population were characterized and found similar to that of unlabeled cells as determined by TUNEL assay, caspase 3/7 enzyme and granzyme B activity assay. Moreover, there were no significant changes in T cell activation (CD24, CD44, CD69 and IFN-γ) or T cell exhaustion (PD-1, LAG-3 and TIM3) markers expression between radiolabeled and unlabeled CAR-T cells. In chemotaxis assays, migratory capability of radiolabeled CAR-T cells to IL-13Rα2Fc was similar to that of non-labeled cells. CONCLUSIONS: Importantly, radiolabeling has minimal impact on biological product attributes including potency of CAR-T cells towards IL-13Rα2 positive tumor cells but not IL-13Rα2 negative cells as measured by cytolytic activity and release of IFN-γ. Thus, IL-13Rα2 targeting CAR-T cells radiolabeled with 89Zr-oxine retain critical product attributes and suggest 89Zr-oxine radiolabeling of CAR-T cells may facilitate biodistribution and tissue trafficking studies in vivo using PET.

Disproportionately High Contributions of 60 Year Old Weapons-137Cs Explain the Persistence of Radioactive Contamination in Bavarian Wild Boars.

Radionuclides released from nuclear accidents or explosions pose long-term threats to ecosystem health. A prominent example is wild boar contamination in central Europe, which is notorious for its persistently high 137Cs levels. However, without reliable source identification, the origin of this decades old problem has been uncertain. Here, we target radiocesium contamination in wild boars from Bavaria. Our samples (2019-2021) range from 370 to 15,000 Bq·kg-1 137Cs, thus exceeding the regulatory limits (600 Bq·kg-1) by a factor of up to 25. Using an emerging nuclear forensic fingerprint, 135Cs/137Cs, we distinguished various radiocesium source legacies in their source composition. All samples exhibit signatures of mixing of Chornobyl and nuclear weapons fallout, with 135Cs/137Cs ratios ranging from 0.67 to 1.97. Although Chornobyl has been widely believed to be the prime source of 137Cs in wild boars, we find that "old" 137Cs from weapons fallout significantly contributes to the total level (10-68%) in those specimens that exceeded the regulatory limit. In some cases, weapons-137Cs alone can lead to exceedances of the regulatory limit, especially in samples with a relatively low total 137Cs level. Our findings demonstrate that the superposition of older and newer legacies of 137Cs can vastly surpass the impact of any singular yet dominant source and thus highlight the critical role of historical releases of 137Cs in current environmental pollution challenges.

Development of a Novel Passive Monitoring Technique to Showcase the 3D Distribution of Tritiated Water (HTO) Vapor in Indoor Air of a Nuclear Facility.

Tritiated water (HTO), a ubiquitous byproduct of the nuclear industry, is a radioactive contaminant of major concern for environmental authorities. Although understanding spatiotemporal heterogeneity of airborne HTO vapor holds great importance for radiological safety as well as diagnosing a reactor's status, comprehensive HTO distribution dynamics inside nuclear facilities has not been studied routinely yet due to a lack of appropriate monitoring techniques. For current systems, it is difficult to simultaneously achieve high representativeness, sensitivity, and spatial resolution. Here, we developed a passive monitoring scheme, including a newly designed passive sampler and a tailored analytical protocol for the first comprehensive 3D distribution characterization of HTO inside a nuclear reactor facility. The technique enables linear sampling in any environment at a one-day resolution and simultaneous preparation of hundreds of samples within 1 day. Validation experiments confirmed the method's good metrological properties and sensitivity to the HTO's spatial dynamics. The air in TU Wien's reactor hall exhibits a range of 3H concentrations from 75-946 mBq m-3 in the entire 3D matrix. The HTO release rate estimated by the mass-balance model (3199 ± 306 Bq h-1) matches the theoretical calculation (2947 ± 254 Bq h-1), suggesting evaporation as the dominant HTO source in the hall. The proposed method provides reliable and quality-controlled 3D monitoring at low cost, which can be adopted not only for HTO and may also inspire monitoring schemes of other indoor pollutants.

Particle radioactivity from radon decay products and reduced pulmonary function among chronic obstructive pulmonary disease patients.

BACKGROUND: Radon (222Rn) decay products can attach to particles in the air, be inhaled, and potentially cause airway damage. RESEARCH QUESTION: Is short-term exposure to particle radioactivity (PR) attributable to radon decay products emitted from particulate matter ≤2.5 µm in diameter (PM2.5) associated with pulmonary function in chronic obstructive pulmonary disease (COPD) patients? STUDY DESIGN AND METHODS: In this cohort study, 142 elderly, predominantly male patients with COPD from Eastern Massachusetts each had up to 4 one-week long seasonal assessments of indoor (home) and ambient (central site) PR and PM2.5 over the course of a year (467 assessments). Ambient and indoor PR were measured as α-activity on archived PM2.5 filter samples. Ratios of indoor/ambient PR were calculated, with higher ratios representing PR from an indoor source of radon decay. We also considered a measure of outside air infiltration that could dilute the concentrations of indoor radon decay products, the indoor/ambient ratio of sulfur concentrations in PM2.5 filter samples. Spirometry pre- and post-bronchodilator (BD) forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were conducted following sampling. Generalized additive mixed models were adjusted for meteorologic variables, seasonality, and individual-level determinants of pulmonary function. We additionally adjusted for indoor PM2.5 and black carbon (BC). RESULTS: PR exposure metrics indicating radon decay product exposure from an indoor source were associated with a reduction in FEV1 and FVC. Patients in homes with high indoor PR (≥median) and low air infiltration (

Mass balance study of [14C]SHR0302, a selective and potent JAK1 inhibitor in humans.

SHR0302, a selective JAK1 inhibitor developed by Jiangsu Hengrui Pharmaceutical Co., was intended for the treatment of rheumatoid arthritis. In this study, we evaluated the pharmacokinetics, mass balance, and metabolism of SHR0302 in six healthy Chinese male subjects after a single 8 mg (80 µCi) oral dose of [14C]SHR0302.SHR0302 was absorbed rapidly (Tmax = 0.505 h), and the average t1/2 of the SHR0302-related components in plasma was approximately 9.18 h. After an oral dose was administered, the average cumulative excretion of the radioactive components was 100.56% ± 1.51%, including 60.95% ± 11.62% in urine and 39.61% ± 10.52% in faeces.A total of 16 metabolites were identified. In plasma, the parent drug SHR0302 accounted for 90.42% of the total plasma radioactivity. In urine, SHR161279 was the main metabolite, accounting for 33.61% of the dose, whereas the parent drug SHR0302 only accounted for 5.1% of the dose. In faeces, the parent drug SHR0302 accounted for 23.73% of the dose, and SHR161279 was the significant metabolite, accounting for 5.67% of the dose. In conclusion, SHR0302-related radioactivity was mainly excreted through urine (60.95%) and secondarily through faeces (39.61%).The metabolic reaction of SHR0302 in the human body is mainly through mono-oxidation and glucuronidation. The main metabolic location of SHR0302 in the human body is the pyrrolopyrimidine ring.

Radiation dose and lifetime risk for radiation-induced cancer due to natural radioactivity in tap water from Jordan.

The purpose of this study was to investigate the radiological quality of drinking water in Ma'an governorate, which includes the archeological city of Petra and is one of Jordan's most important tourist destinations. To the best of the authors' knowledge, this is the first study in southern Jordan that investigates radioactivity in drinking water and its potential to cause cancer. A liquid scintillation detector was used to measure gross alpha and gross beta activities in tap water samples from Ma'an governorate. A high-purity Germanium detector was used to measure the activity concentrations of 226Ra and 228Ra. Gross alpha, gross beta, 226Ra, and 228Ra activities were < 110-724 mBq/l, < 220-362 mBq/l, < 11-241 mBq/l, and < 32-49 mBq/l, respectively. The results were compared to internationally recommended levels and literature values. Annual effective doses ([Formula: see text]) from 226 and 228Ra intake were calculated for infants, children, and adults. The highest doses were found for children while the lowest were found for infants. For each water sample, the lifetime risk of radiation-induced cancer (LTR) was calculated for the whole population. All of the LTR values were lower than the value recommended by the World Heath Organisation. It is concluded that there are no significant radiation-related health risks associated with consumption of tap water from the studied region.

Development of an economical method to synthesize O-(2-[18 F]fluoroethyl)-L-tyrosine (18 FFET).

Positron emission tomography (PET) using O-(2-[18 F]fluoroethyl)-L-tyrosine ([18 F]FET) has shown great success in differentiating tumor recurrence from necrosis. In this study, we are reporting the experience of synthesis [18 F]FET by varying the concentration of TET precursor in different chemistry modules. TET precursor (2-10 mg) was used for the synthesis of [18 F]FET in an automated (MX Tracerlab) module (n = 6) and semiautomated (FX2N Tracerlab) module (n = 19). The quality control was performed for all the preparations. For human imaging, 220 ± 50 MBq of [18 F]FET was briefly injected into the patient to acquire PET-MR images. The radiochemical purity was greater than 95% for the final product in both modules. The decay corrected average yield was 10.7 ± 4.7% (10 mg, n = 3) and 8.2 ± 2.6% (2 mg, n = 3) with automated chemistry module and 36.7 ± 7.3% (8-10 mg, n = 12), 26.4 ± 3.1% (5-7 mg, n = 4), and 35.1 ± 3.8% (2-4 mg, n = 3) with semiautomated chemistry modules. The PET imaging showed uptake at the lesion site (SUVmax = 7.5 ± 2.6) and concordance with the MR image. The [18 F]FET was produced with a higher radiochemical yield with 2.0 mg of the precursor with substantial yield and is suitable for brain tumor imaging.

Phytoremediation of radioactive elements, possibilities and challenges: special focus on agricultural aspects.

The radioactive contamination has been reported frequently from agricultural lands and ground water. The main reason behind the radioactive pollution is unprotected mining of radioactive elements, unsafe discard of nuclear industrial waste, military applications, dumping of medically used radioisotopes, globally situated (>400) nuclear power plants and use of phosphate fertilizers in farming. Radionuclides are well known potent carcinogens that may cause the various types of cancers to human and animals due to the long exposure to radioactive contaminated sites. To get rid of from the radioactive pollution there is a need of practically successful and cost effective bioremediation technologies that should able to decontaminate the effected lands and water to benefit the mankind. Microbial and phytoremediation are well studied methods for decreasing or gradually eliminating the radioactive contaminants. In this review, we discussed the different strategies of microbial and phytoremediation of radionuclides and recent advancements, that can play the major role in bioremediation of soil and water.

Different remediation technologies based on physical (precipitation, extraction and membrane separation technologies) and chemical (chemical extraction and leaching, hydrolysis, etc.) methods to remediate the radioactive compounds from soils and water are being developed and evaluated. Most of these technologies are cost intensive and only applicable to little contaminated sites. On the other hand phytoremediation and microbial bioremediation are scientifically proven for applying at large scale and economical. Phytoremediation is one of the bioengineering treatments in which terrestrial and aquatic plants have been successfully used for cleaning the radioactive pollutants from diverse environments. Present review article is a updating the recent developments came in the different bioremediation methods. Moreover aim of this manuscript is also emerging the research gaps and identified the future research frontiers to unlock the complexity of phyto and microbial remediation advancements. Although several plants and numerous bacteria and fungi have been identified as the potential radioactive accumulator but their complete mechanism of bioremediation is still unknown. Present article will help the researchers to understand the process of bioremediation of radionuclides in more depths and will aware about the requirements of the coming future.HighlightsPhyto and microbial bioremediation of radioactive elements, possibilities and challenges.Causes of radioactive contamination in soil and water.Nanophytoremediation is an advanced technology of phytoremediation.Drawbacks of phytoremediation.

Assessment of the Pharmacokinetics, Disposition, and Duration of Action of the Tumour-Targeting Peptide CEND-1.

CEND-1 (iRGD) is a bifunctional cyclic peptide that can modulate the solid tumour microenvironment, enhancing the delivery and therapeutic index of co-administered anti-cancer agents. This study explored CEND-1's pharmacokinetic (PK) properties pre-clinically and clinically, and assessed CEND-1 distribution, tumour selectivity and duration of action in pre-clinical tumour models. Its PK properties were assessed after intravenous infusion of CEND-1 at various doses in animals (mice, rats, dogs and monkeys) and patients with metastatic pancreatic cancer. To assess tissue disposition, [3H]-CEND-1 radioligand was administered intravenously to mice bearing orthotopic 4T1 mammary carcinoma, followed by tissue measurement using quantitative whole-body autoradiography or quantitative radioactivity analysis. The duration of the tumour-penetrating effect of CEND-1 was evaluated by assessing tumour accumulation of Evans blue and gadolinium-based contrast agents in hepatocellular carcinoma (HCC) mouse models. The plasma half-life was approximately 25 min in mice and 2 h in patients following intravenous administration of CEND-1. [3H]-CEND-1 localised to the tumour and several healthy tissues shortly after administration but was cleared from most healthy tissues by 3 h. Despite the rapid systemic clearance, tumours retained significant [3H]-CEND-1 several hours post-administration. In mice with HCC, the tumour penetration activity remained elevated for at least 24 h after the injection of a single dose of CEND-1. These results indicate a favourable in vivo PK profile of CEND-1 and a specific and sustained tumour homing and tumour penetrability. Taken together, these data suggest that even single injections of CEND-1 may elicit long-lasting tumour PK improvements for co-administered anti-cancer agents.