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Background: Mold brachytherapy using high-energy β - -emitting radioisotopes is a promising treatment modality for skin cancers and keloids. Simple methodologies for consistent and stable incorporation of radionuclides into the matrix are desired for preparation of therapeutic sources. Methods: The authors report a facile strategy for the stable incorporation of Yttrium-90 ( 90 Y) into amidoxime-functionalized polyacrylonitrile-polyvinylidene fluoride (PAN-PVDF) membranes. The strategy consisted of surface modification of PAN-PVDF membranes by reaction with hydroxylamine, characterization of the functionalized membranes, and optimization of experimental variables for maximum loading of 90 Y onto the membranes. Quality control tests essential for confirming the suitability of the 90 Y therapeutic sources for human application, such as uniformity of activity distribution, absence of leaching of activity, and estimation of surface contamination, were performed. Theoretical calculations to estimate the dose imparted by the 90 Y therapeutic sources at varying depths of tissue were also carried out to predict the possible therapeutic outcome of treatment. Results: A facile method for large-scale preparation of 90 Y-based mold brachytherapy sources could be established. Conclusions: The source fabrication methodology standardized in this work could be tailored for fabrication of custom-made 90 Y sources for individualized treatment of superficial tumors, Bowen's disease, and keloids.

Cardiac troponin (cTn) is made up of three subunits, cTnC, cTnI, and cTnT. The regulatory N-terminal domain of cTnC (cNTnC) controls cardiac muscle contraction in a calcium-dependent manner. We show that calcium-saturated cNTnC can adopt two different orientations, with the "active" orientation consistent with the 2020 cryo-EM structure of the activated cardiac thin filament by Yamada et al. Using solution NMR 15 N R 2 relaxation analysis, we demonstrate that the two domains of cTnC tumble independently (average R 2 10 s -1 ), being connected by a flexible linker. However, upon addition of cTnI 1-77 , the complex tumbles as a rigid unit (R 2 30 s -1 ). cTnI phosphomimetic mutants S22D/S23D, S41D/S43D and dilated cardiomyopathy- (DCM-)associated mutations cTnI K35Q, cTnC D75Y, and cTnC G159D destabilize the active orientation of cNTnC, with intermediate 15 N R 2 rates (R 2 17-23 s -1 ). The active orientation of cNTnC is stabilized by the flexible tails of cTnI, cTnI 1-37 and cTnI 135-209 . Surprisingly, when cTnC is incorporated into complexes lacking these tails (cTnC-cTnI 38-134 , cTnC-cTnT 223-288 , or cTnC-cTnI 38-134 -cTnT 223-288 ), the cNTnC domain is still immobilized, revealing a new interaction between cNTnC and the IT-arm that stabilizes a "dormant" orientation. We propose that the calcium sensitivity of the cardiac troponin complex is regulated by an equilibrium between active and dormant orientations, which can be shifted through post-translational modifications or DCM-associated mutations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: The quality control parameters of in-house-produced 90 Y-Acetate from high-level liquid waste (HLLW) using supported liquid membrane (SLM) technology were validated and compared with the pharmacopeia standard. The radiolabeling of DOTATATE yielding 90 Y-DOTATATE in acceptable radiochemical purity (RCP), with expected pharmacological behavior in in vivo models, establish the quality of 90 Y-Acetate. Clinical translation of 90 Y-Acetate in formulation of 90 Y-DOTATATE adds support toward its use as clinical-grade radiochemical. Methods: Quality control parameters of 90 Y-Acetate, namely radionuclide purity (RNP), were evaluated using β - spectrometry, γ-spectroscopy, and liquid scintillation counting. RCP and metallic impurities were established using high-performance liquid chromatography and inductively coupled plasma optical emission spectrometry, respectively. The suitability of 90 Y-Acetate as an active pharmaceutical ingredient radiochemical was ascertained by radiolabeling with DOTATATE. In vivo biodistribution of 90 Y-DOTATATE was carried out in nude mice bearing AR42J xenografted tumor. Clinical efficacy of 90 Y-DOTATATE was established after using in patients with large-volume neuroendocrine tumors (NET). Bremsstrahlung imaging was carried out in dual-head gamma camera with a wide energy window setting (100-250 keV). Results: In-house-produced 90 Y-Acetate was clear, colorless, and radioactive concentration (RAC) in the range of 40-50 mCi/mL. RCP was >98%. 90 Sr content was <0.85 μCi/Ci of 90 Y. Gross λ content was <0.8 nCi/Ci of 90 Y and no γ peak was observed. Fe 3+ , Cu 2+ , Zn 2+ , Cd 2+ , and Pb 2+ contents were <1.7 μg/Ci. The radiolabeling yield (RLY) of 90 Y-DOTATATE was >94%, RCP was >98%. The in vitro stability of 90 Y-DOTATATE was up to 72 h postradiolabeling, upon storage at -20°C. Post-therapy (24 h) Bremsstrahlung image of patients with large NET exhibit complete localization of 90 Y-DOTATATE in tumor region. Conclusions: This study demonstrates that the in-house-produced 90 Y-Acetate from HLLW can be used for the formulation of various therapeutic 90 Y-based radiopharmaceuticals. Since 90 Y is an imported radiochemical precursor available at a high cost in India, this study which demonstrates the suitability of indigenously sourced 90 Y, ideally exemplifies the recovery of "wealth from waste." The Clinical Trial Registration number: (P17/FEB/2019).

In the present study, a prototype 106Ru/106Rh source was fabricated using high level liquid waste from reactor fuel, fixed in a stainless steel housing with a window and backing made of silver. The study involves measurement of the operational quantities Hp(0.07), Hp(3) and the percentage depth dose (PDD) using an extrapolation chamber. It also involves determination of necessary correction factors to arrive at Hp(0.07) and Hp(3) following International Organisation for Standardisation (ISO) and methods suggested in literature. The study facilitates incorporation of the 106Ru/106Rh source as a beta reference source for quality assurance programme in TLD personnel monitoring as per the guidelines of ISO., (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Novel Solvent Impregnated Resin (SIR) material was prepared by impregnating a trialkyl phosphine oxide functionalized ionic liquid (IL) into an inert polymeric material XAD-7. A series of SIR materials were prepared by varying the IL quantity. Sorption of both U(VI) and Pu(IV) were found to increase with increasing IL concentration in SIR up to an optimum IL concentration of 435 mg g -1 of SIR beyond which no effect of IL concentration was observed. A change of mechanism of sorption for U(VI) by SIR was observed in comparison to solvent extraction. The dependency of U(VI) sorption with nitric acid concentration showed a reverse trend compared to solvent extraction studies while for Pu(IV) the trend remained same as observed with solvent extraction. Sorption of both the radionuclides was found to follow pseudo second order mechanism and Langmuir adsorption isotherm. Distribution co-efficient measurements on IL impregnated SIR showed highly selective sorption of U(VI) and Pu(IV) over other trivalent f-elements and fission products from nitric acid medium., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The manuscript presents the results on the sorption of U(VI), Am(III) & Eu(III) from pH medium by a novel amido-amine functionalized multiwalled carbon nanotube (MWCNT). The novel functional group was introduced in the MWCNT by two step processes and characterized by various instrumental techniques like Scanning Electron Microscopy (SEM), Raman and X-ray Photoelectron Spectroscopy (XPS). The sorption process was found to be highly dependent on the pH of the solution with maximum sorption for both 233U, 241Am & 152+154Eu at pH 7.0. Kinetics of sorption was found to be fast with equilibrium reached in ∼15min and the sorption was found to be following pseudo 2nd order kinetics for the radionuclides. The sorption for both 233U and 152+154Eu followed Langmuir sorption model with maximum sorption capacity of 20.66mg/g and 16.1mg/g respectively. This has been explained by DFT calculations which shows that more negative solvation energy of U(VI) compared to Am(III) and Eu(III) and stronger U-MWCNT-AA complex is responsible for higher sorption capacity of U(VI) compared to Am(III) and Eu(III).The synthesized amido-amine functionalized MWCNT is a very promising candidate for removal of actinides and lanthanides from waste water solution with high efficiency., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A new ligand grafted polymeric resin (BenzoDODA SDVB) was synthesized by covalently attaching plutonium selective ligand (BenzoDODA) on to styrene divinyl benzene (SDVB) polymer matrix. BenzoDODA SDVB resin was evaluated for separation and recovery of plutonium(IV) from nitric acid medium. Sorption of Pu(IV) was found to decrease with the increase in nitric acid concentration, with very small sorption above 7.0M HNO3. Sorption kinetics was fast enough to achieve the equilibrium within 60min of contact where the kinetic data fitted well to pseudo-second-order model. Sorption isotherm data fitted well to Langmuir model suggesting chemical interaction between the BenzoDODA moiety and plutonium(IV) ions. Sorption studies with some of representative radionuclides of high level waste showed that BenzoDODA SDVB is selective and therefore could be a promising solid sorbent for separation and recovery of plutonium. Further, the theoretical calculations done on BenzoDODA SDVB resin suggested Pu(NO3)4·BenzoDODA (1:1) sorbed complex conformed to generally observed square antiprism geometry of the plutonium complexes, with contributions from oxygen atoms of four nitrate ions as well as from four oxygen atoms present in BenzoDODA (two phenolic ether oxygen atoms and two carbonyl oxygen atoms of amidic moiety)., (Copyright © 2016. Published by Elsevier B.V.)

A new class of conformationally constrained oxa-bridged tricyclo-dicarboxamide (OTDA) ligand was rationally designed for the selective extraction of tetravalent actinides pertinent to the Plutonium Uranium Redox EXtraction (PUREX) process. Two of the designed diamide ligands were synthesized and extraction studies were performed for Pu(iv) from HNO3 medium. The mechanism of extraction was investigated by studying various parameters such as feed HNO3, NaNO3 and OTDA concentrations. The nature of the extracted species was found to be [Pu(NO3)4(OTDA)]. One of the OTDA ligands was elaborately tested and showed the selective extraction of Pu(iv) and Np(iv) over other actinide species, viz., U(vi), Np(v), Am(iii), lanthanides and fission products contained in a nuclear waste from the PUREX process. DFT calculations predicted the charge density on each of the coordinating 'O' atoms of OTDA supporting its high Pu(iv) selectivity over other ions studied and also provided the energy optimized structure of OTDA and its Pu(iv) complex.

Am(III) is one of the most hazardous radionuclide present in nuclear fuel cycle. A new conformationally constrained diamide, (N,N,N',N'-tetra-2-ethylhexyl)7-oxabicyclo[2.2.1]heptane-2,3-dicarboxamide (OBDA) was studied for Am(III) transport from HNO3 medium across a Supported Liquid Membrane. Transport rate was observed to be significantly fast with ∼95% transport of Am(III) within 1h using 0.1M OBDA in the presence of 15% isodecyl alcohol (IDA)/n-dodecane as carrier. The mechanism of transport was investigated by studying various parameters like feed HNO3/NaNO3 concentration, OBDA concentration in the membrane, membrane pore size, membrane thickness etc. From these studies, the mechanism of transport was found to be diffusion controlled with diffusion co-efficient value of 5.1×10(-6)cm(2)/s. The membrane was found to be highly selective for tri- and tetra-valent actinides, and trivalent lanthanides. OBDA based membrane was found to be stable for at least for ten consecutive cycles of operation., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A new class of conformationally constrained 7-oxabicyclo[2.2.1]heptane-2,3-dicarboxamides (OBDA) of three secondary amines was synthesized, and their extraction behavior for trivalent and tetravalent actinides in HNO3 medium was studied. Amongst the diamides, N,N-bis-2-ethylhexyl substituted diamide showed the best results for actinide extraction. This diamide also exhibited a very low level of extraction for Sr(ii) and Ru(iii) which is desirable, thus providing higher selectivity for actinides. The stripping of extracted metal ions was achieved using 0.1 M oxalic acid for Pu(iv) or pH ∼ 2 solution for Am(iii). Third phase formation was not observed for the OBDA ligand even for a higher concentration of Eu up to 5 g L(-1) with retention of good DEu. The tridentate nature of the OBDA ligand was ascertained by studying the IR and NMR spectra of the Eu(iii) complex with the ligand. The OBDA showed the formation of a mixture of mono- and di-solvated species of Eu(iii) as indicated by the slope analysis method and ESI-MS. Density functional theoretical (DFT) study was carried out to determine the energy optimized structure of the free ligand and its Am(3+) complex.

A monoamide, N,N'-dioctyl, α-hydroxy acetamide, shows unusual extraction properties towards trivalent lanthanide and actinide ions above 3 M HNO3. The extracted ions could be quantitatively back extracted using 0.5 M HNO3. This amide shows negligible extraction towards Sr(II) and Ru(III) ions, making it advantageous over other reported extractants. The structures of Sm(III) and Eu(III) nitrate compounds show that the metal ion is surrounded by three of the ligands, one nitrate and one water molecule. The ligand acts as a neutral bidentate ligand and bonds through the amido and hydroxyl oxygen atoms.

Objective: The aim of the present study was to evaluate the behaviour of (90)Y-labeled particles when injected into an arthritic knee joint of Wistar rats with severe inflammation induced using Complete Freund's Adjuvant (CFA)., Methods: (90)Y-ferric hydroxide macroaggregates ((90)Y-FHMA), (90)Y-hydroxyapatite ((90)Y-HA) and (90)Y-phosphate particles ((90)YPO(4)) were prepared, subjected to quality control analyses and in vitro stability studies. Biodistribution studies were carried out by intra-articular injection into knee joints of Wistar rats induced with chronic inflammatory arthritis using CFA and by monitoring the radioactivity for retention and leakage., Results: All the three preparations exhibited ~99% localization in knee joints even at 24 h p.i. with very small amounts observed in the liver and lungs, possibly due to leakage of the radiolabeled particles from the inflamed knee joint. Absence of any radioactivity in the femur indicated the in vivo stability of the particle preparations., Conclusions: The biodistribution patterns were very similar in the normal and arthritic rats and were associated with negligible leakage (up to 24 h) from the knee joint indicating the potential of all the (90)Y-radiolabeled preparations reported here, for use in radiation synoviorthesis.

Yttrium-90 used for therapy should be of very high radionuclidic (RN) purity (>99.998%) as the most probable contaminant, strontium-90, is a bone seeker with a maximum permissible body burden of 74 kBq (2 microCi) only. None of the current known methods of RN purity estimations is adequate to reliably measure the 90Sr RN impurity at such low levels. Our aim was to develop a reliable technique to accurately determine the amount of 90Sr in 90Y used for therapy. This new technique combines chelate-based extraction with paper chromatography using paper impregnated with 2-ethylhexyl, 2-ethylhexylphosphonic acid (KSM-17), which is a 90Y-specific chelator. A PC strip impregnated with KSM-17 at the point of spotting is used for chromatography. Upon development with normal saline, 90Sr moves to the solvent front leaving 90Y completely chelated and retained at the point of spotting. The activity at the solvent front (90Sr) is quantified by liquid scintillation counting, and the data are compared with the total applied activity to provide the RN purity of the test solution. The method has a sensitivity of > or =74 kBq (2 microCi) of 90Sr per 37 GBq (1 Ci) of 90Y. This novel, innovative, and simple technique offers a reliable solution to the unanswered problem of estimation of 90Sr content in 90Y used for cancer therapy.

Background: 90Y is one of the radioisotopes used extensively for therapy due to its favourable nuclear characteristics. Particles and colloids incorporating 90Y are being used for radiation synovectomy, especially in European countries., Methods: In our present work, 90Y phosphate particles were prepared and evaluated for use in radiation synovectomy. The radioactive particles were prepared by reacting carrier added 90YCl3 with phosphoric acid., Results: The radiolabelling yield obtained was >95%. The particles were found to be stable in saline for up to 7 days of study at 37 degrees C. Particle size analysis of inactive yttrium phosphate showed that most of the particles were in the size range of 2-20 microm. Biodistribution studies carried out by intra-articular injection of the particles into the knee joints of rats showed that approximately 99% of the particles were retained in the joints with negligible radioactivity in the major organs even at 48 h post-injection. Scintigraphic studies in rabbit showed that >99% of the radioactive particles were retained in the knee joint even at 96 h post-injection. No significant radioactivity above background was detected in the blood., Conclusion: The promising results warrant further studies on 90Y phosphate particles for use in radiation synovectomy.

Studies on the determination of trace metallic impurities in nuclear materials such as uranium, thorium and plutonium are described. The bulk of the matrix is separated by batch extraction from their nitric acid solutions using 2-ethylhexyl hydrogen 2-ethylhexyl phosphonate (KSM-17, equivalent to PC88-A). The final aqueous phase containing the metallic impurities is fed to a high-temperature source inductively coupled plasma and the analysis is carried out employing a computer-controlled multichannel direct-reading spectrometer. The studies also included the recovery of impurities at various acidities and spectral interferences of the above matrices over the analyte elements. Based on the above studies, methods were standardized for the determination of 19 elements, viz. Al, B, Be, Ca, Cd, Cr, Cu, Fe, Mg, Mn, Ni, Pb, Si, Zn, Ce, Dy, Eu, Gd and Sm, in U/Th/Pu solutions. The relative standard deviation for various elements is in the range 1-5%.