Quality Assurance Considerations in Radiopharmaceutical Therapy Dosimetry Using PLANETDose: An International Atomic Energy Agency Study.

Implementation of radiopharmaceutical therapy dosimetry varies depending on the clinical application, dosimetry protocol, software, and ultimately the operator. Assessing clinical dosimetry accuracy and precision is therefore a challenging task. This work emphasizes some pitfalls encountered during a structured analysis, performed on a single-patient dataset consisting of SPECT/CT images by various participants using a standard protocol and clinically approved commercial software. Methods: The clinical dataset consisted of the dosimetric study of a patient administered with [177Lu]Lu-DOTATATE at Tygerberg Hospital, South Africa, as a part of International Atomic Energy Agency-coordinated research project E23005. SPECT/CT images were acquired at 5 time points postinjection. Patient and calibration images were reconstructed on a workstation, and a calibration factor of 122.6 Bq/count was derived independently and provided to the participants. A standard dosimetric protocol was defined, and PLANETDose (version 3.1.1) software was installed at 9 centers to perform the dosimetry of 3 treatment cycles. The protocol included rigid image registration, segmentation (semimanual for organs, activity threshold for tumors), and dose voxel kernel convolution of activity followed by absorbed dose (AD) rate integration to obtain the ADs. Iterations of the protocol were performed by participants individually and within collective training, the results of which were analyzed for dosimetric variability, as well as for quality assurance and error analysis. Intermediary checkpoints were developed to understand possible sources of variation and to differentiate user error from legitimate user variability. Results: Initial dosimetric results for organs (liver and kidneys) and lesions showed considerable interoperator variability. Not only was the generation of intermediate checkpoints such as total counts, volumes, and activity required, but also activity-to-count ratio, activity concentration, and AD rate-to-activity concentration ratio to determine the source of variability. Conclusion: When the same patient dataset was analyzed using the same dosimetry procedure and software, significant disparities were observed in the results despite multiple sessions of training and feedback. Variations due to human error could be minimized or avoided by performing intensive training sessions, establishing intermediate checkpoints, conducting sanity checks, and cross-validating results across physicists or with standardized datasets. This finding promotes the development of quality assurance in clinical dosimetry.

Deep Eutectic Solvent-Based Highly Sensitive Turn-On Fluorescent Probe for D2O.

Owing to the importance of heavy water in spectroscopy, nuclear energy generation, chemical characterization, and biological industry, a design of a robust, cheap, nontoxic, and sensitive D2O sensor is very important. In this work, taking advantage of the singular emission fluorescence of the deep eutectic solvent prepared in our laboratory, we propose a first of its kind highly sensitive turn-on fluorescent sensor to effectively sense D2O at an ultratrace level based on rapid exchange of the labile DES proton with deuterium. This method can be used as a full-range heavy water detection strategy with a limit of detection of 0.079% (v/v) or 870 ppm. The isotopic purity (IP) obtained from DES fluorescence measurements is also in close agreement with that of the conventional FT-IR method. The current DES-based sensor thus allows both sensing and isotopic purity of D2O and can serve as one of the most sensitive monitoring strategies for heavy water analysis.

Utilizing Energy Transfer in Mn2+/Ho3+/Yb3+ Tri-doped ZnAl2O4 Nanophosphors for Tunable Luminescence and Highly Sensitive Visual Cryogenic Thermometry.

Lanthanide (Ln3+)-doped upconversion (UC) phosphors converting near-infrared (NIR) light to visible light hold very high promise toward biomedical applications. The scientific findings on luminescent thermometers revealed their superiority for noninvasive thermal sensing. However, only few reports showcase their potential for applications in extreme conditions (temperatures below -70 °C) restricted by low thermal sensitivity. Here, we demonstrate the tailoring of luminescence properties via introducing Ho3+-Mn2+ energy transfer (ET) routes with judicious codoping of Mn2+ ions in ZnAl2O4/Ho3+,Yb3+ phosphor. Preferentially, a singular red UC emission is required to improve the bioimaging sensitivity and minimize tissue damage. We could attain UC emission with 94% red component by a two-photon UC process. Higher temperature annealing brings the color coordinates to the green domain, highlighting the potential for color-tunable luminescence switch. Moreover, this work investigates the thermometric properties of ZnAl2O4/Yb3+, Ho3+ in the range of 80-300 K and influence of inducing extra ET pathways by Mn2+ codoping. Interestingly, the luminescence intensities for nonthermally coupled (5F4,5S2) and the 5F5 radiative transitions of Ho3+ ions display opposite behavior at 80 and 300 K, which revealed competition between temperature-sensitive decay pathways. The codoping of Mn2+ ions is fruitful in causing a fourfold increase of absolute sensitivity. Notably, the color tunability from green through yellow to red is helpful in rough temperature estimation by naked eyes. The maximum relative (Sr) and absolute sensitivities (Sa) were estimated to be 1.89% K-1 (140 K) and 0.0734 K-1 (300 K), respectively. Even at 80 K, a Sa of 0.00447 K-1 and Sr of 0.6025% K-1 were achievable in our case, which are higher than most of the other Ln3+-based systems. The above-mentioned results demonstrate the potential of ZnAl2O4/Yb3+,Ho3+ for cryogenic optical thermometry and a strategy to design new Ln3+-based UC thermometers by taking advantage of ET routes.

MicroRNA397 regulates tolerance to drought and fungal infection by regulating lignin deposition in chickpea root.

Plants deposit lignin in the secondary cell wall as a common response to drought and pathogen attacks. Cell wall localised multicopper oxidase family enzymes LACCASES (LACs) catalyse the formation of monolignol radicals and facilitate lignin formation. We show an upregulation of the expression of several LAC genes and a downregulation of microRNA397 (CamiR397) in response to natural drought in chickpea roots. CamiR397 was found to target LAC4 and LAC17L out of twenty annotated LACs in chickpea. CamiR397 and its target genes are expressed in the root. Overexpression of CamiR397 reduced expression of LAC4 and LAC17L and lignin deposition in chickpea root xylem causing reduction in xylem wall thickness. Downregulation of CamiR397 activity by expressing a short tandem target mimic (STTM397) construct increased root lignin deposition in chickpea. CamiR397-overexpressing and STTM397 chickpea lines showed sensitivity and tolerance, respectively, towards natural drought. Infection with a fungal pathogen Macrophomina phaseolina, responsible for dry root rot (DRR) disease in chickpea, induced local lignin deposition and LAC gene expression. CamiR397-overexpressing and STTM397 chickpea lines showed more sensitivity and tolerance, respectively, to DRR. Our results demonstrated the regulatory role of CamiR397 in root lignification during drought and DRR in an agriculturally important crop chickpea.

Development of an Agrobacterium-delivered codon-optimized CRISPR/Cas9 system for chickpea genome editing.

Chickpea is considered recalcitrant to in vitro tissue culture amongst all edible legumes. The clustered, regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9)-based genome editing in chickpea can remove the bottleneck of limited genetic variation in this cash crop, which is rich in nutrients and protein. However, generating stable mutant lines using CRISPR/Cas9 requires efficient and highly reproducible transformation protocols. As an attempt to solve this problem, we developed a modified and optimized protocol for chickpea transformation. This study transformed the single cotyledon half-embryo explants using CaMV35S promoter to drive two marker genes (ß-glucuronidase gene; GUS and green fluorescent protein; GFP) through binary vectors pBI101.2 and modified pGWB2, respectively. These vectors were delivered in the explants through three different strains of Agrobacterium tumefaciens, viz., GV3101, EHA105, and LBA4404. We found better efficiency with the strain GV3101 (17.56%) compared with two other strains, i.e., 8.54 and 5.43%, respectively. We recorded better regeneration frequencies in plant tissue culture for the constructs GUS and GFP, i.e., 20.54% and 18.09%, respectively. The GV3101 was further used for the transformation of the genome editing construct. For the development of genome-edited plants, we used this modified protocol. We also used a modified binary vector pPZP200 by introducing a CaMV35S-driven chickpea codon-optimized SpCas9 gene. The promoter of the Medicago truncatula U6.1 snRNA gene was used to drive the guide RNA cassettes. This cassette targeted and edited the chickpea phytoene desaturase (CaPDS) gene. A single gRNA was found sufficient to achieve high efficiency (42%) editing with the generation of PDS mutants with albino phenotypes. A simple, rapid, highly reproducible, stable transformation and CRISPR/Cas9-based genome editing system for chickpea was established. This study aimed to demonstrate this system's applicability by performing a gene knockout of the chickpea PDS gene using an improved chickpea transformation protocol for the first time.

Unclasping potentials of genomics and gene editing in chickpea to fight climate change and global hunger threat.

Genomics and genome editing promise enormous opportunities for crop improvement and elementary research. Precise modification in the specific targeted location of a genome has profited over the unplanned insertional events which are generally accomplished employing unadventurous means of genetic modifications. The advent of new genome editing procedures viz; zinc finger nucleases (ZFNs), homing endonucleases, transcription activator like effector nucleases (TALENs), Base Editors (BEs), and Primer Editors (PEs) enable molecular scientists to modulate gene expressions or create novel genes with high precision and efficiency. However, all these techniques are exorbitant and tedious since their prerequisites are difficult processes that necessitate protein engineering. Contrary to first generation genome modifying methods, CRISPR/Cas9 is simple to construct, and clones can hypothetically target several locations in the genome with different guide RNAs. Following the model of the application in crop with the help of the CRISPR/Cas9 module, various customized Cas9 cassettes have been cast off to advance mark discrimination and diminish random cuts. The present study discusses the progression in genome editing apparatuses, and their applications in chickpea crop development, scientific limitations, and future perspectives for biofortifying cytokinin dehydrogenase, nitrate reductase, superoxide dismutase to induce drought resistance, heat tolerance and higher yield in chickpea to encounter global climate change, hunger and nutritional threats.

Biochemical analysis of anthocyanin and proanthocyanidin and their regulation in determining chickpea flower and seed coat colour.

Flower and seed coat colour are important agronomic traits in chickpea (Cicer arietinum L.). Cultivated chickpeas are of two types namely, desi (dark seeded, purple flowered) and kabuli (light seeded, white flowered). There has been limited information about the molecular mechanism underlying colour variation of flower and seed coats in desi and kabuli chickpea. We profiled the anthocyanin and proanthocyanidin (PA) contents in chickpea flowers and seed coats. Tissue-specific silencing of two genes encoding a basic helix-loop-helix (CabHLH) protein and a tonoplast-localized multidrug and toxic compound extrusion (CaMATE1) transporter in a desi genotype resulted in the reduction in expression of anthocyanin and PA biosynthetic genes and anthocyanin and PA contents in the flower and seed coat, and produced flowers and seeds with kabuli characteristics. Transcriptional regulation of a subset of anthocyanin and PA biosynthetic genes by a natural CabHLH variant and transport assay of a natural CaMATE1 variant explained the association of these alleles with the kabuli phenotype. We carried out a detailed molecular characterization of these genes, and provided evidence that kabuli chickpea flower and seed colour phenotypes can be derived by manipulation of single genes in a desi chickpea background.

Epigenomics as Potential Tools for Enhancing Magnitude of Breeding Approaches for Developing Climate Resilient Chickpea.

Epigenomics has become a significant research interest at a time when rapid environmental changes are occurring. Epigenetic mechanisms mainly result from systems like DNA methylation, histone modification, and RNA interference. Epigenetic mechanisms are gaining importance in classical genetics, developmental biology, molecular biology, cancer biology, epidemiology, and evolution. Epigenetic mechanisms play important role in the action and interaction of plant genes during development, and also have an impact on classical plant breeding programs, inclusive of novel variation, single plant heritability, hybrid vigor, plant-environment interactions, stress tolerance, and performance stability. The epigenetics and epigenomics may be significant for crop adaptability and pliability to ambient alterations, directing to the creation of stout climate-resilient elegant crop cultivars. In this review, we have summarized recent progress made in understanding the epigenetic mechanisms in plant responses to biotic and abiotic stresses and have also tried to provide the ways for the efficient utilization of epigenomic mechanisms in developing climate-resilient crop cultivars, especially in chickpea, and other legume crops.

Harvesting Light from BaHfO3/Eu3+ through Ultraviolet, X-ray, and Heat Stimulation: An Optically Multifunctional Perovskite.

Materials with optical multifunctionality such as photoluminescence (PL), radioluminescence, and thermoluminescence (TL) are a boon for a sustainable society. BaHfO3 (barium hafnium oxide [BHO]) under UV irradiation demonstrated visible PL endowed by oxygen vacancies (OVs). Eu3+ doping in BHO (BHOE) introduces f-state impurity levels just below the conduction band for both Eu@Ba and Eu@Hf sites, causing efficient host-to-dopant energy transfer, generating intense 5D0 → 7F1 magnetic dipole transitions (MDT) with internal quantum yield of ∼70%. X-ray photoelectron spectroscopy and electron paramagnetic resonance showed the formation of OVs in both BHO and BHOE samples with more vacancies in the doped sample. The positron lifetime measurements suggested that Eu3+ ions are distributed at both Ba2+ and Hf4+ sites. The association of OVs with Hf4+ and Eu3+ ions due to high charge/radius ratio is considered to be responsible for lowering the symmetry around Eu3+ ions to C 4v in BHOE. Density functional theory studies of defect formation energy justified the same. Time-resolved emission spectroscopy showed distinct spectra for Eu@Ba and Eu@Hf sites corresponding to symmetric and asymmetric environments, respectively. This could be highly relevant in designing color tunable phosphor by forcing dopant ions at one specific site because Eu@Ba displayed orange emission whereas Eu@Hf displayed red emission. We could further harness BHOE for X-ray scintillator application by designing a thin film, which showed efficient conversion of high-energy X-ray into visible light. Under beta irradiation; both BHO and BHOE showed distinct TL glow curves as shallow traps were formed in the former and deep traps in the latter, which could have long-term implications in harnessing this material for persistent luminescence. We believe that BHO/BHOE demonstrated an extraordinary credential as a perovskite for multifunctional applications in the area of defect-induced light emission, UV phosphor, X-ray scintillator, and TL crystals.

Role of silicon in elevating resistance against sheath blight and blast diseases in rice (Oryza sativa L.).

Rice blast caused by Magnaporthe oryzae and sheath blight caused by Rhizoctonia solani, are the two major diseases of rice that cause enormous losses in rice production worldwide. Identification and utilization of broad-spectrum resistance resources have been considered sustainable and effective strategies. However, the majority of the resistance genes and QTLs identified have often been found to be race-specific, and their resistance is frequently broken down due to continuous exposure to the pathogen. Therefore, integrated approaches to improve plant resistance against such devastating pathogen have great importance. Silicon (Si), a beneficial element for plant growth, has shown to provide a prophylactic effect against many pathogens. The application of Si helps the plants to combat the disease-causing pathogens, either through its deposition in different parts of the plant or through modulation/induction of specific defense genes by yet an unknown mechanism. Some reports have shown that Si imparts resistance to rice blast and sheath blight. The present review summarizes the mechanism of Si transport and deposition and its effect on rice growth and development. A special emphasis has been given to explore the existing evidence showing Si mediated blast and sheath blight resistance and the mechanism involved in resistance. This review will help to understand the prophylactic effects of Si against sheath blight and blast disease at the mechanical, physiological, and genetic levels. The information provided here will help develop a strategy to explore Si derived benefits for sustainable rice production.

ELEPHANT ENDOTHELIOTROPIC HERPESVIRUS HEMORRHAGIC DISEASE OUTBREAK IN AN INDIAN ZOO.

Elephant endotheliotropic herpesvirus hemorrhagic disease (EEHV HD) is an acute viral infection of growing Asian elephants (Elephas maximus). Four apparently healthy subadult Asian elephants aged between 6 and 10 yr at Nandankanan Zoological Park (NKZP), India, died of EEHV HD during August-September 2019. All four elephants were rescued from different reserved forests of Odisha state at less than 1 yr of age and hand reared in the NKZP. Elephants exhibited the clinical signs of lethargy, head swelling, fever, loss of appetite, abdominal distension, scant urination and defecation, signs of colic, lameness, trunk discharge, cyanosis/ulceration of tongue, erratic behavior, and recumbence before death. Period of illness varied between 28 and 42 h. Thrombocytopenia was the common significant hematological observation. No significant biochemical alterations were recorded except for higher creatinine concentrations. Analysis of blood samples in RT-PCR assay using two different sets of primers and probes that targeted terminase gene and major DNA-binding protein gene followed by cPCR and sequencing was positive for EEHV-1A in all four animals. Postmortem examination of all four carcasses showed hemorrhages in internal organs, including the hard palate, heart, lungs, stomach, mesenteric lymph nodes, mesentery, colon serosa, spleen, liver, kidney, and meninges. Histopathology showed congestion and/or hemorrhages in heart, lung, brain, kidney, and liver. There was presence of intranuclear inclusion bodies in the sinusoidal epithelial cells. The outbreak of EEHV HD that resulted in the acute death of four juvenile captive Asian elephants within <30 d, the first of its kind documented in India, is increasing the fear of similar outbreaks in the future.

Lignin deposition in chickpea root xylem under drought.

In our recent publication, we have shown that a member of the Laccase family, LACCASE2 (LAC2) acted as a negative regulator of lignin deposition in the root xylem tissue of Arabidopsis thaliana. LAC2 messenger RNA (mRNA) level was post-transcriptionally regulated by microRNA 397b, which showed increased expression under water and phosphate deficiency, resulting in the downregulation of LAC2 expression In this report, we have investigated root growth and lignin deposition in an economically important legume crop chickpea (Cicer arietinum L.) in response to natural drought in soil-grown condition. In contrast to the growth retardation of Arabidopsis root in mannitol-supplemented medium, chickpea root showed an increase in length in low soil moisture condition. Lignin estimation in the primary root showed an increase in lignin content, which was substantiated by staining of root xylem. Drought treatment enhanced the expression of four out of six LAC genes tested, while the expression of two was downregulated. Our preliminary study indicateed a molecular mechanism of lignin deposition in chickpea root xylem during drought.

Blast resistance gene Pi54 over-expressed in rice to understand its cellular and sub-cellular localization and response to different pathogens.

Rice blast resistance gene, Pi54 provides broad-spectrum resistance against different strains of Magnaporthe oryzae. Understanding the cellular localization of Pi54 protein is an essential step towards deciphering its place of interaction with the cognate Avr-gene. In this study, we investigated the sub-cellular localization of Pi54 with Green Fluorescent Protein (GFP) as a molecular tag through transient and stable expression in onion epidermal cells (Allium cepa) and susceptible japonica cultivar rice Taipei 309 (TP309), respectively. Confocal microscopy based observations of the onion epidermal cells revealed nucleus and cytoplasm specific GFP signals. In the stable transformed rice plants, GFP signal was recorded in the stomata, upper epidermal cells, mesophyll cells, vascular bundle, and walls of bundle sheath and bulliform cells of leaf tissues. These observations were further confirmed by Immunocytochemical studies. Using GFP specific antibodies, it was found that there was sufficient aggregation of GFP::Pi54protein in the cytoplasm of the leaf mesophyll cells and periphery of the epidermal cells. Interestingly, the transgenic lines developed in this study could show a moderate level of resistance to Xanthomonas oryzae and Rhizoctonia solani, the causal agents of the rice bacterial blight and sheath blight diseases, respectively. This study is a first detailed report, which emphasizes the cellular and subcellular distribution of the broad spectrum blast resistance gene Pi54 in rice and the impact of its constitutive expression towards resistance against other fungal and bacterial pathogens of rice.

Root-specific expression of chickpea cytokinin oxidase/dehydrogenase 6 leads to enhanced root growth, drought tolerance and yield without compromising nodulation.

Cytokinin group of phytohormones regulate root elongation and branching during post-embryonic development. Cytokinin-degrading enzymes cytokinin oxidases/dehydrogenases (CKXs) have been deployed to investigate biological activities of cytokinin and to engineer root growth. We expressed chickpea cytokinin oxidase 6 (CaCKX6) under the control of a chickpea root-specific promoter of CaWRKY31 in Arabidopsis thaliana and chickpea having determinate and indeterminate growth patterns, respectively, to study the effect of cytokinin depletion on root growth and drought tolerance. Root-specific expression of CaCKX6 led to a significant increase in lateral root number and root biomass in Arabidopsis and chickpea without any penalty to vegetative and reproductive growth of shoot. Transgenic chickpea lines showed increased CKX activity in root. Soil-grown advanced chickpea transgenic lines exhibited higher root-to-shoot biomass ratio and enhanced long-term drought tolerance. These chickpea lines were not compromised in root nodulation and nitrogen fixation. The seed yield in some lines was up to 25% higher with no penalty in protein content. Transgenic chickpea seeds possessed higher levels of zinc, iron, potassium and copper. Our results demonstrated the potential of cytokinin level manipulation in increasing lateral root number and root biomass for agronomic trait improvement in an edible legume crop with indeterminate growth habit.

Bioethanol production from waste lignocelluloses: A review on microbial degradation potential.

Tremendous explosion of population has led to about 200% increment of total energy consumptions in last twenty-five years. Apart from conventional fossil fuel as limited energy source, alternative non-conventional sources are being explored worldwide to cater the energy requirement. Lignocellulosic biomass conversion for biofuel production is an important alternative energy source due to its abundance in nature and creating less harmful impacts on the environment in comparison to the coal or petroleum-based sources. However, lignocellulose biopolymer, the building block of plants, is a recalcitrant substance and difficult to break into desirable products. Commonly used chemical and physical methods for pretreating the substrate are having several limitations. Whereas, utilizing microbial potential to hydrolyse the biomass is an interesting area of research. Because of the complexity of substrate, several enzymes are required that can act synergistically to hydrolyse the biopolymer producing components like bioethanol or other energy substances. Exploring a range of microorganisms, like bacteria, fungi, yeast etc. that utilizes lignocelluloses for their energy through enzymatic breaking down the biomass, is one of the options. Scientists are working upon designing organisms through genetic engineering tools to integrate desired enzymes into a single organism (like bacterial cell). Studies on designer cellulosomes and bacteria consortia development relating consolidated bioprocessing are exciting to overcome the issue of appropriate lignocellulose digestions. This review encompasses up to date information on recent developments for effective microbial degradation processes of lignocelluloses for improved utilization to produce biofuel (bioethanol in particular) from the most plentiful substances of our planet.

Yellow Emission from Low Coordination Site of Sr2 SiO4 :Eu2+ , Ce3+ : Influence of Lanthanide Dopants on the Electron Density and Crystallinity in Crystal Site Engineering Approach.

Lanthanide doping through a crystal site engineering approach tunes the emission wavelength suitable for LED applications, but weak emission from low coordination sites remains a huge challenge. Herein the use of a sensitizer is reported to enhance the emission strength and unravel the crystallinity and phase, as this approach demands a large amount of dopants. Doping of Eu2+ ions at SrO10 and SrO9 sites of Sr2 SiO4 (S2 S), respectively, tunes the emission from green to yellow and controlled doping of a Ce3+ sensitizer quadruples the quantum efficiency of yellow emission. Remarkably, doping of Eu2+ at the SrO9 site produces polycrystals, whereas co-doping of Ce3+ and Eu2+ at the same site produces single crystals. DFT calculations further delineate the underlying changes wherein strong interaction of dopant with its neighbours determines the electron density, and thus the crystallinity and phase, rather than usual explanation of aliovalent conditions, which is further substantiated by TEM results. Irrespective of dopant valence, use of large amounts of dopants and their interaction with the host is responsible for the crystallinity and phase change (α'-S2 S to ß-S2 S). The XPS valence band spectra experimentally evidences the changes in bonding nature of O 2p and O 2s orbitals of silicate and its electron density, due to doping at the two sites. In short, the outcomes resulting from this work could be extended for the development of other two-coordination site lanthanide-doped materials and crystallization of inorganic materials.

Dosimetric analysis of patients with gastro entero pancreatic neuroendocrine tumors (NETs) treated with PRCRT (peptide receptor chemo radionuclide therapy) using Lu-177 DOTATATE and capecitabine/temozolomide (CAP/TEM).

OBJECTIVE:: Two radiosensitizing chemotherapeutic drugs, capecitabine (CAP) and temozolomide (TEM), are administered concurrently to enhance the therapeutic efficacy of peptide receptor radionuclide therapy (PRRT). This study aims to assess the biodistribution and normal-organ and tumor radiation dosimetry for Lu-177 DOTATATE administered concurrently with CAP/TEM. METHODS:: 20 patients with non-resectable histologically confirmed gastroenteropancreatic neuroendocrine tumors with normal kidney function, a normal haematological profile and somatostatin receptor expression of the tumor lesions, as scintigraphically assessed by a Ga-68 DOTANOC scan, were included in two groups-case group (n = 10) and control group (n = 10). Patients included in case group were those who were advised concomitant CAPTEM therapy by the treating medical oncologist. Patients were administered CAP orally at a dose of 600mg m-2 bovine serum albumin twice a day for 14 days starting 9 days prior to PRRT and oral TEM as a single dose at a dose of 75 mg m-2 was given concurrently for the last 5 days commencing on the day of PRRT (days 9-14). In the control group, patients were treated with Lu-177 DOTATATE only. For PRRT, 6.4 GBq-7.6 GBq (173-207 mCi) of Lu-177 DOTATATE was administered as infusion into each patient over 10-15 min in a solution with positively charged amino acids for renal protection. Dosimetric calculations were done using the HERMES software. RESULTS:: Physiological uptake of Lu-177 DOTATATE was seen in all patients in liver, spleen kidneys, and bone marrow. Radiation absorbed doses (mean ± standard deviation) were obtained as 0.29 ± 0.12 mGy/MBq for kidneys, 0.30 ± 0.18 mGy/MBq for liver, 0.63 ± 0.37 mGy/MBq for spleen, 0.019 ± 0.001 mGy/MBq for bone marrow and 3.85 ± 1.74 mGy/MBq for tumours in the case group and they were 0.31± 0.26, 0.24 ± 0.14, 0.64 ± 0.42, 0.017 ± 0.016, 5.6 ± 11.27 mGy/MBq in kidneys, liver, spleen, bone marrow and neuroendocrine tumour, respectively, in the control group. Mann-Whitney U test between the variables of two groups showed an insignificant difference (p > 0.05). CONCLUSIONS:: The authors demonstrated no significant difference between the tumor and organ doses with Lu-177 DOTATATE in the patients treated with and without concomitant chemotherapy. ADVANCES IN KNOWLEDGE:: To our knowledge, this is the first dedicated study exhibiting dosimetric analysis in patients undergoing PRRT in combination with chemotherapy.

Role of Synthesis Method on Luminescence Properties of Europium(II, III) Ions in ß-Ca2SiO4: Probing Local Site and Structure.

The europium ion probes the symmetry disorder in the crystal structure, although the distortion due to charge compensation in the case of aliovalent dopant remains interesting, especially preparation involves low and high temperatures. This work studies the preparation of the ß-Ca2SiO4 (from here on C2S) particle from Pechini (C2SP) and hydrothermal (C2SH) methods, and its luminescence variance upon doping with Eu2+ and Eu3+ ions. The blue shift of the charge-transfer band (CTB) in the excitation spectra indicates a larger Eu3+-O2- distance in Eu3+ doped C2SH. The changes in vibrational frequencies due to stretching and bending vibrations in the FTIR and the Raman spectra and binding energy shift in the XPS analysis confirmed the distorted SiO44- tetrahedra in C2SH. The high hydrothermal temperature and pressure produce distortion, which leads to symmetry lowering although doping of aliovalent ion may slightly change the position of the Ca atoms. The increasing asymmetry ratio value from C2SP to C2SH clearly indicates that the europium ion stabilized in a more distorted geometry. It is also supported by Judd-Ofelt analysis. The concentration quenching and site-occupancy of Eu3+ ions in two nonequivalent sites of C2S were discussed. The charge state and concentration of europium ions in C2SP and C2SH were determined using X-ray photoelectron spectroscopy measurements. The C2S particles were studied by X-ray powder diffraction, FTIR, Raman, BET surface area, TGA/DTA, electron microscopy, XPS, and luminescence spectroscopy. The impact of citrate ion on the morphology and particle size of C2SH has been hypothesized on the basis of the microscopy images. This study provides insights that are needed for further understanding the structure of C2S and thereby improves the applications in optical and biomedical areas and cement hydration.

Deciphering the Role of Charge Compensator in Optical Properties of SrWO4:Eu3+:A (A = Li+, Na+, K+): Spectroscopic Insight Using Photoluminescence, Positron Annihilation, and X-ray Absorption.

Studies have been carried out to understand the specific role of the alkali charge compensator on the luminescence properties of an alkali ion (Li+, Na+, and K+) codoped SrWO4:Eu phosphor. The oxidation state of the europium ion was found to be +3 on the basis of X-ray absorption near edge structure (XANES) measurements. This is the first report of its kind where opposite effects of Li+ ion and Na+/K+ ions on photoluminescence intensity have been observed. Li+ ion codoping enhanced the photoluminescence intensity from SrWO4:Eu3+ phosphor while Na+/K+ ion codoping did not. On the other hand, the luminescence lifetime is maximum for the Na+ ion codoped sample and minimum for the Li+ ion codoped sample. The results could be explained successfully using time-resolved luminescence, positron annihilation lifetime spectroscopy (PALS), and extended X-ray absorption fine structure (EXAFS) spectroscopy measurements. Changes in the Eu-O bond length and Debye-Waller Factor (σ2) upon Li+/Na+/K+ codoping were monitored through EXAFS measurements. PALS also highlighted the fact that Li+ codoping is not contributing to reduction in the cation vacancies and might be occupying interstitial sites rather than lattice positions due to its very small size. On europium doping there is lowering in symmetry of SrO8 polyhedra from S4 to C6, which is reflected in an intense electric dipole transition in comparison to the magnetic dipole transition. This is also corroborated using trends in Judd-Ofelt parameters. The results have shown that the luminescence lifetime is better when the vacancy concentration is lower as induced by Na+ and K+ codoping, while the emission intensity is higher in the samples when distortion around Eu3+ is reduced as induced by Li+ codoping.