Integrating resilience with functional ecosystem measures: A novel paradigm for management decisions under multiple-stressor interplay in freshwater ecosystems.

Moving beyond monitoring the state of water quality to understanding how the sensitive ecosystems "respond" to complex interplay of climatic and anthropogenic perturbations, and eventually the mechanisms that underpin alterations leading to transitional shifts is crucial for managing freshwater resources. The multiple disturbance dynamics-a single disturbance as opposed to multiple disturbances for recovery and other atrocities-alter aquatic ecosystem in multiple ways, yet the global models lack representation of key processes and feedbacks, impeding potential management decisions. Here, the procedure we have embarked for what is known about the biogeochemical and ecological functions in freshwaters in context of ecosystem resilience, feedbacks, stressors synergies, and compensatory dynamics, is highly relevant for process-based ecosystem models and for developing a novel paradigm toward potential management decisions. This review advocates the need for a more aggressive approach with improved understanding of changes in key ecosystem processes and mechanistic links thereof, regulating resilience and compensatory dynamics concordant with climate and anthropogenic perturbations across a wide range of spatio-temporal scales. This has relevance contexting climate change and anthropogenic pressures for developing proactive and adaptive management strategies for safeguarding freshwater resources and services they provide.

Monte Carlo-based dosimetric studies of a locally developed170Tm LDR brachytherapy seed source.

170Tm is being explored as a source for applications in brachytherapy. Although it has adequate physical properties, such as a short half-life (128.6 d), high specific activity and a mean photon energy of about 66 keV, it has a drawback of low photon yield (only about six photon emissions/100 beta emissions). The objective of this work is to study the dosimetric characteristics of a locally developed170Tm brachytherapy seed source using the Monte Carlo-based EGSnrc code system. In this study, we calculate the dose rate constant, air-kerma strength, radial dose function, anisotropic function and 2D dose-rate distributions in water. Separate simulations are carried out by considering the photon (gamma and characteristic x-ray) and beta spectra of the source. For regions close to the source (surface of the source

Metal Contamination in Seven Tributaries of the Ganga River and Assessment of Human Health Risk from Fish Consumption.

We investigated the distribution of Zn, Cu, Ni, Pb, Cr, and Cd in water, sediment, and two dietary fish (an omnivore, Labeo rohita and a benthic carnivore, Clarias batrachus) and potential health risk to human consumers during summer low flow (2017-2018) at 28 sites across 7 tributary confluences of the Ganga River. We selected Devprayag, an upper reach site, as a reference for data comparison. We found significant spatial variations in the distribution of study metals and the concentrations remained higher in tributaries, confluences, and downstream cities. The pollution load index showed all sites except Devprayag in the polluted category. Ecological risk analysis indicated 1 site with very high risk, 7 with considerable risk, and 10 with moderate-risk category. The Zn did appear the most, and Cd the least accumulated metal in the fish. The metal accumulation was higher in C. batrachus. The levels of Cd, Cr, and Pb in the study fishes were higher compared with the international standards. The health risk analysis indicated safe levels for individual metals except for Cd where the target hazard quotient (THQ) did exceed 1 for C. batrachus at the Ramganga and Varuna confluences. When all metals were considered, the THQ was > 1 (> 2 for C. batrachus), indicating the full possibility of adverse health effects to human consumers. Our study highlights the importance of tributaries in creating a mosaic of metal-rich habitats in the Ganga River and food chain associated with a health risk to human consumers.

Preparation of 177 Lu-labeled Nimotuzumab for radioimmunotherapy of EGFR-positive cancers: Comparison of DOTA and CHX-A″-DTPA as bifunctional chelators.

This study was aimed at evaluating the role of bifunctional chelators DOTA-NCS and CHX-A″-DTPA-NCS used for conjugating 177 Lu with Nimotuzumab on the radiochemical yields, purity, in vitro stability, and specificity of the radioimmunoconjugates to EGFR. Two immunoconjugates were prepared wherein Nimotuzumab was conjugated with the acyclic ligand p-NCS-Bn-CHX-A″-DTPA and macrocyclic ligand p-NCS-Bn-DOTA. These were radiolabeled with 177 Lu, purified on PD-10 column, and characterized by SE-HPLC. In vitro stability was determined up to 4 days post preparation. Specificity of the radioimmunoconjugates was ascertained by in vitro studies in A431 cells while the biodistribution patterns were studied in normal Swiss mice up to 96 hours post injection. Four to five molecules of CHX-A″-DTPA/DOTA were attached to one molecule of Nimotuzumab. Radiochemical purity of both 177 Lu-CHX-A″-DTPA-Nimotuzumab and 177 Lu-DOTA-Nimotuzumab was determined to be greater than 98%. Both the radioimmunoconjugates exhibited good in vitro stability at 37°C up to 4 days post preparation in saline, and their clearance was largely by the hepatobiliary route. The DOTA- and CHX-A″-DTPA-based radioimmunoconjugates could be prepared with good radiochemical purity, in vitro stability, and specificity to EGFR. Further studies in EGFR-positive cancers would pave way for them for use in the clinics.

Preparation and preliminary bioevaluation studies of 68 Ga-NOTA-rituximab fragments as radioimmunoscintigraphic agents for non-Hodgkin lymphoma.

Rituximab is used for the treatment of non-Hodgkin lymphoma (NHL). This study focuses on development of 68 Ga-labeled rituximab fragments, (68 Ga-NOTA-F (ab')-rituximab and 68 Ga-NOTA-F (ab')2 -rituximab, as PET-imaging agents for NHL. Rituximab was digested with immobilized pepsin and papain to yield F (ab')2 and Fab fragments respectively that were characterized by size exclusion HPLC (SE-HPLC) and SDS-PAGE. They were conjugated with p-SCN-Bn-NOTA, labeled with 68 Ga and characterized by SE-HPLC. Intact rituximab was labeled with gallium-68 for comparison. Specificity of 68 Ga-labeled immunoconjugates was ascertained by immunoreactivity and cell binding studies in Raji cells, while biodistribution studies were performed in normal Swiss mice. Gradient SDS-PAGE under nonreducing condition showed molecular weights of F (ab')2 -rituximab and F (ab')-rituximab as approximately 100 and 40 Kd, respectively. Radiochemical purity (RCP) of 68 Ga-NOTA-F (ab')2 -rituximab and 68 Ga-NOTA-F (ab')-rituximab were 98.2 ± 0.5% and 98.8 ± 0.2% respectively with retention times of 17.1 ± 0.1 min and 19.3 ± 0.1 min in SE-HPLC. 68 Ga-labeled rituximab fragments were stable in saline and serum up to 2-hour post preparation and exhibited specificity to CD20 antigen. Immunoreactivity of 68 Ga-labeled immunoconjugates was greater than 80%. Clearance of the fragmented radioimmunoconjugates was predominantly through renal route. Preliminary results from this study demonstrate the potential of 68 Ga- NOTA-F (ab')2 -rituximab and 68 Ga-NOTA-F (ab')-rituximab as PET imaging agents for NHL.

68Ga labeled Erlotinib: A novel PET probe for imaging EGFR over-expressing tumors.

Molecular imaging using radiolabeled Tyrosine Kinase Inhibitors (TKI) is a promising strategy for detection and staging of EGFR-positive cancers. A novel analogue of one such TKI, Erlotinib has been developed for PET imaging by derivatizing the parent Erlotinib molecule for conjugation with the bifunctional chelator p-SCN-Bn-NOTA towards radiolabeling with 68Ga. NOTA-Erlotinib conjugate was synthesized and characterized by NMR and ESI-MS techniques. The conjugate was radiolabeled with 68Ga in 95±2% yield, as evidenced by HPLC characterization. The logP value of 68Ga-NOTA-Erlotinib was - (0.6±0.1). The 68Ga-NOTA-Erlotinib conjugate was characterized using its natGa-NOTA-Erlotinib surrogate. Cell viability studies showed that the NOTA-Erlotinib conjugate retained the biological efficacy of the parent Erlotinib molecule. Further, 68Ga-NOTA-Erlotinib exhibited an uptake of 9.8±0.4% in A431 cells which was inhibited by 55.1±0.2% on addition of cold Erlotinib (10µg) confirming the specificity of the radioconjugate for EGFR expressing cells. In the biodistribution studies carried out in tumor bearing SCID mice, 68Ga-NOTA-Erlotinib conjugate showed moderate tumor accumulation (1.5±0.1% ID/g at 30minp.i.; 0.7±0.2% ID/g at 1hp.i.). Hepatobiliary clearance of the radioconjugate was observed. The 68Ga-NOTA-Erlotinib conjugate was found to have high in vivo stability as determined by the metabolite analysis study using urine sample of the Swiss mice injected with the preparation. The overall properties of 68Ga-NOTA-Erlotinib are promising and merit further exploration. To the best of our knowledge, this is the first report on the design of a 68Ga labeled Erlotinib for PET imaging of EGFR and opens avenues for the successful development of 68Ga labeled TKI for imaging of EGFR over-expressing tumors.

68Ga labeled fatty acids for cardiac metabolic imaging: Influence of different bifunctional chelators.

Development of 68Ga labeled fatty acids is of immense interest due to the availability of 68Ga through a generator and its superiority over SPECT based tracers in carrying out dynamic imaging on a PET scanner. Our present work explores the influence of different chelators on the cardiac uptake and pharmacokinetics of the 68Ga-labeled fatty acids. Two new 68Ga labeled fatty acids were synthesized by conjugation of 11-aminoundecanoic acid with the bifunctional chelators (BFCs) viz. p-SCN-Bn-DTPA (S-2-(4-isothiocyanatobenzyl)-diethylenetriaminepentaacetic acid) and p-SCN-Bn-NODAGA (S-2-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1-glutaric acid-4,7-acetic acid) and their comparison was carried out with the previously reported 68Ga-NOTA-undecanoic acid. Both the conjugates were radiolabeled with 68Ga in high yields and purities (>95%). Their formation was established by preparation and characterization of their inactive analogs with natGa at macroscopic levels. Biodistribution studies of the complexes in Swiss mice showed lower initial myocardial uptake for 68Ga-NODAGA-undecanoic acid (3.8±0.6%ID/g) and 68Ga-DTPA-undecanoic acid (1.3±0.5%ID/g) complexes in comparison to previously reported 68Ga-NOTA-undecanoic acid complex (7.4±2.8%ID/g) at 2min p.i. However, significant retention of the tracer in the myocardium was observed in the case of 68Ga-NODAGA-undecanoic complex, which led to improved heart/non-target ratios of the complex over time in comparison to the other 68Ga complexes. Similarly, the DTPA complex exhibited increased washout from the liver in comparison to other 68Ga derivatives. The ß oxidation mechanism in myocytes was investigated by isolating the myocardial extract post intravenous injection of the respective 68Ga complexes and analyzing them by radio-HPLC, which showed metabolic transformation of the parent fatty acid complex peak in all the three complexes. This study has provided an insight into the design characteristics of 68Ga labeled fatty acids to achieve the desired myocardial imaging characteristics.

Preparation & in vitro evaluation of 9°Y-DOTA-rituximab.

BACKGROUND & OBJECTIVES: Radioimmunotherapy is extensively being used for the treatment of non-Hodgkin's lymphoma (NHL). Use of rituximab, a chimeric anti-CD20 antibody directed against the CD20 antigen in combination with suitable beta emitters is expected to result in good treatment response by its cross-fire and bystander effects. The present work involves the conjugation of p-isothiocyanatobenzyl DOTA (p-SCN-Bn-DOTA) to rituximab, its radiolabelling with [90] Y and in vitro and in vivo evaluation to determine its potential as a radioimmunotherapeutic agent. METHODS: Rituximab was conjugated with p-SCN-Bn-DOTA at 1:1 antibody: DOTA molar ratio. The number of DOTA molecules linked to one molecule of rituximab was determined by radioassay and spectroscopic assay. Radiolabelling of rituximab with 90 Y was carried out and its in vitro stability was evaluated. In vitro cell binding studies were carried out in Raji cells expressing CD20 antigen. Biodistribution studies were carried out in normal Swiss mice. RESULTS: Using both radioassay and spectroscopic method, it was determined that about five molecules of DOTA were linked to rituximab. Radiolabelling of the rituximab conjugate with [90] Y and subsequent purification on PD-10 column gave a product with radiochemical purity (RCP) > 98 per cent which was retained at > 90 per cent up to 72 h when stored at 37°C. In vitro cell binding experiments of 90 Y-DOTA-rituximab with Raji cells exhibited specific binding of 20.7 ± 0.1 per cent with [90] Y-DOTA-rituximab which reduced to 15.5 ± 0.2 per cent when incubated with cold rituximab. The equilibrium constant K d for 90 Y-DOTA-Rituximab was determined to be 3.38 nM. Radiolabelled antibody showed clearance via hepatobiliary and renal routes and activity in tibia was found to be quite low indicating in vivo stability of [90] Y-DOTA-rituximab. INTERPRETATION & CONCLUSIONS: p-SCN-Bn-DOTA was conjugated with rituximab and radiolabelling with 90 Y was carried out. In vitro studies carried out in Raji cells showed the specificity of the radiolabelled conjugate suggesting the potential uitability of the formulation as a radiopharmaceutical for therapy of NHL.

Preliminary evaluation of indigenous 90 Y-labelled microspheres for therapy of hepatocellular carcinoma.

BACKGROUND & OBJECTIVES: Yttrium-90 ( 90 Y)-based radioembolization has been employed to treat hepatocellular carcinoma (HCC) as commercial radioactive glass and polymeric resin microspheres. However, in India and other Asian countries, these preparations must be imported and are expensive, validating the need for development of indigenous alternatives. This work was aimed to develop an economically and logistically favourable indigenous alternative to imported radioembolizing agents for HCC therapy. METHODS: The preparation of 90 Y-labelled Biorex 70 microspheres was optimized and in vitro stability was assessed. Hepatic tumour model was generated in Sprague-Dawley rats by orthotopic implantation of N1S1 rat HCC cell line. In vivo localization and retention of the 90 Y-labelled Biorex 70 microspheres was assessed for seven days, and impact on N1S1 tumour growth was studied by histological examination and biochemical assays. RESULTS: Under optimal conditions, >95% 90 Y-labelling yield of Biorex70 resin microspheres was obtained, and these showed excellent in vitro stability of labelling (>95%) at seven days. In animal studies, 90 Y-labelled Biorex 70 microspheres were retained (87.72±1.56% retained in liver at 7 days). Rats administered with 90 Y-labelled Biorex 70 microspheres exhibited lower tumour to liver weight ratio, reduced serum alpha-foetoprotein level and greater damage to tumour tissue as compared to controls. INTERPRETATION & CONCLUSIONS: 90 Y-labelled Biorex 70 microspheres showed stable retention in the liver and therapeutic effect on tumour tissue, indicating the potential for further study towards clinical use.

The skewed N:P stoichiometry resulting from anthropogenic drivers regulate production of transparent exopolymer particles (TEP) in Ganga River.

Transparent exopolymer particles (TEP), generated from excretion products of microalgae, trigger flocculation of diatoms and sinking of organic matter. Investigations along 797 km stretch of Ganga River indicated that TEP declined with increasing N:P stoichiometric ratio downstream. The TEP showed positive relationship with chlorophyll a (R(2) = 0.9661; p < 0.0001) and biogenic silica (R(2) = 0.8797; p < 0.0001) and negative relationship (R(2) = 0.8547; p < 0.0001) with N:P ratio. The study that forms the first report on N:P linked changes in TEP in Ganga River showed that the shifting N:P stoichiometric ratios resulting from anthropogenic release may alter TEP production and, by implication, ecosystem functioning including carbon sequestration in the river.

Development of 68Ga-labeled fatty acids for their potential use in cardiac metabolic imaging.

While [(11)C]palmitate continues to be a promising tracer for cardiovascular Positron Emission Tomography (PET) imaging, unfavourable logistics due to the short half-life of (11)C (20 min) and cumbersome labeling methodologies are the major impediments that limit its widespread use. In order to circumvent such limitations, an attempt has been made to explore the potential of (68)Ga-labeled fatty acid analogs for metabolic imaging owing to the availability of (68)Ga through a (68)Ge/(68)Ga generator on an on-demand basis. In this study, two fatty acid conjugates were synthesized by conjugation of p-SCN-benzyl NOTA with the ω-amino group of 11-amino undecanoic acid and 12-amino dodecanoic acid, respectively, under alkaline conditions. Both derivatives were radiolabeled in high yields with (68)Ga obtained from an in-house (68)Ge/(68)Ga generator. Biodistribution studies in Swiss mice showed reasonable myocardial uptake at 2 min for both derivatives (7.4 ± 2.8% ID/g for 11-carbon fatty acid-NOTA conjugate and 6.4 ± 2.1% ID/g for 12-carbon fatty acid-NOTA conjugate), which cleared rapidly over 30 min. However, significant activity was found in blood for both tracers, with heart/blood ratios observed to be below 0.5 at all time points, diminishing the potential of the synthesized complexes for cardiac imaging.

The influence of DOC trends on light climate and periphyton biomass in the Ganga River, Varanasi, India.

Investigations on periphyton along an eutrophication gradient (NO(3)(-) = 0.23-0.96 mg L(-1); PO(4)(-3) = 0.16-0.86 mg L(-1)) of Ganga River indicated that benthic algal biomass decreased with increasing concentrations of nutrients and dissolved organic carbon (DOC). Periphyton biomass showed negative relationship (R(2) = 0.98; p < 0.0001) with DOC and positive relationship (R(2) = 0.96; p < 0.0001) with Secchi depth. Sites with high DOC showed dominance of cyanophycean Phormidium uncinatum. The study shows that the rising concentration of DOC over time may alter the light climate and consequently the fate of benthic primary producers in Ganga River.

68Ga-Labeled Trastuzumab Fragments for ImmunoPET Imaging of Human Epidermal Growth Factor Receptor 2 Expression in Solid Cancers.

Background: Trastuzumab, the first humanized antibody approved for therapeutic use has shown promising results for the treatment of patients with human epidermal growth factor receptor 2 (HER2) positive cancers. The aim of this study was to formulate immunoPET agents based on trastuzumab fragments and demonstrate their potential for early diagnosis of HER2-positive tumors. Materials and Methods: F(ab')2 and F(ab') fragments of trastuzumab were prepared by enzymatic digestion and conjugated with chelator NOTA for labeling with 68Ga. For comparison, intact trastuzumab was also radiolabeled. In vitro stability, immunoreactivity, and binding affinity of radio formulations toward HER2 receptors were evaluated by performing in vitro studies in cancer cell lines. Biodistribution and PET imaging studies were performed in animal model bearing tumors. Results: 68Ga-NOTA-F(ab')-trastuzumab, 68Ga-NOTA-F(ab')2-trastuzumab, and 68Ga-NOTA-trastuzumab could be prepared with >98% radiochemical purity (% RCP) and were found to be stable when studied up to 4 h. In vitro binding studies revealed high affinity and specificity of formulations toward HER2 receptors. Specific tumor uptake of 68Ga-NOTA-F(ab')-trastuzumab and 68Ga-NOTA-F(ab')2-trastuzumab in HER2-positive tumors was observed in biodistribution and PET imaging studies. Conclusions: This study describes optimization of protocol for the formulation of 68Ga-NOTA-F(ab')-trastuzumab and 68Ga-NOTA-F(ab')2-trastuzumab for targeting HER2-overexpressing tumors. Further studies with these radioformulations are warranted to confirm their potential as immunoPET agents for management of HER2-positive breast and other solid tumors.

Effects of COVID-19 lockdown on water quality, microbial extracellular enzyme activity, and sediment-P release in the Ganga River, India.

This study investigates possible improvement in water quality and ecosystem functions in the Ganga River as influenced by COVID-19 lockdown in India. A total of 132 samples were collected during summer-2020 low flow (coinciding COVID-19 lockdown) for water (sub-surface and sediment-water interface) and 132 samples separately for sediment (river bottom and land-water interface) considering 518-km main river stem including three-point sources (one releases urban sewage and the other two add metal-rich industrial effluents) and a pollution-impacted tributary. Parameters such as dissolved oxygen deficit and the concentrations of carbon, nutrients (N and P), and heavy metals were measured in water. Sediment P-release was measured in bottom sediment whereas extracellular enzymes (EE; alkaline phosphatase, FDAase, protease, and ß-D-glucosidase) and CO2 emission were measured at land-water interface to evaluate changes in water quality and ecosystem functions. The data comparisons were made with preceding year (2019) measurements. Sediment-P release and the concentrations of carbon, nutrients, and heavy metals declined significantly (p<0.05) in 2020 compared to those recorded in 2019. Unlike the preceding year, we did not observe benthic hypoxia (DO <2.0 mg L-1) in 2020 even at the most polluted site. The EE activities, which declined sharply in the year 2019, showed improvement during the 2020. The stability coefficient and correlative evidences also showed a large improvement in the water quality and functional variables. Positive changes in functional attributes indicated a transient recovery when human perturbations withdrawn. The study suggests that timing the ecosystem recovery windows, as observed here, may help taking management decision to design mitigation actions for rivers to recover from anthropogenic perturbations.

A Facile Strategy for Preparation of Yttrium-90 Therapeutic Sources for Radionuclide Therapy.

Background: Mold brachytherapy using high-energy ß--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 (90Y) 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 90Y onto the membranes. Quality control tests essential for confirming the suitability of the 90Y 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 90Y 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 90Y-based mold brachytherapy sources could be established. Conclusions: The source fabrication methodology standardized in this work could be tailored for fabrication of custom-made 90Y sources for individualized treatment of superficial tumors, Bowen's disease, and keloids.

Mannosylated dextran derivatives labeled with fac-[M(CO)3]+ (M = (99m)Tc, Re) for specific targeting of sentinel lymph node.

Despite being widely used in the clinical setting for sentinel lymph node detection (SLND), (99m)Tc-based colloids (e.g., (99m)Tc-human serum albumin colloids) present a set of properties that are far from ideal. Aiming to design novel compounds with improved biological properties, we describe herein the first class of fully characterized (99m)Tc(CO)3-mannosylated dextran derivatives with adequate features for SLND. Dextran derivatives, containing the same number of pendant mannose units (13) and a variable number (n) of tridentate chelators (9, n = 1; 10, n = 4, 11, n= 12), have been synthesized and fully characterized. Radiolabeled polymers of the type fac-[(99m)Tc(CO)3(k³-L)] (12, L = 9, 13, L = 10, 14, L = 11) have been obtained quantitatively in high radiochemical purity (≥ 98%) upon reaction of the dextran derivatives with fac-[(99m)Tc(CO)3(H2O)3]+. The highly stable compounds 13 and 14 were identified by comparing their HPLC chromatograms with the ones obtained for the corresponding rhenium surrogates fac-[Re(CO)3(k³-10)] (13a) and fac-[Re(CO)3(k³-11)] (14a), which have been characterized both at the chemical (NMR and IR spectroscopy, and HPLC) and physical level (DLS, AFM and LDV). Compounds 13a and 14a present a positive zeta potential (+ 7.1 mV, pH 7.4) and a hydrodynamic diameter in the range 8.4-8.7 nm. Scintigraphic imaging and biodistribution studies in Wistar rats have shown good accumulation in the sentinel node at 60 min postinjection (6.71 ± 2.35%, 13; and 7.53 ± 0.69%, 14), with significant retention up to 180 min. A clear delineation of the sentinel lymph node without significant washout to other regions was observed in the scintigraphic images. The popliteal extraction of 94.47 ± 2.45% for 14 at 1 h postinjection, as compared to 61.81 ± 2.4% for 13, indicated that 14 is a very promising compound to be further explored as SLN imaging agent.

An electrochemical technique for fabrication of Mn-54 sources towards characterization of gamma counting nuclear instruments.

Long lived sealed radioactive sources are used for the energy calibration and efficiency determination of counting systems used in the nuclear sector. Using a sulphate bath, a facile electrochemical method was developed by electrodeposition of 54Mn on 5 mm (φ) stainless steel substrates for the preparation of 54Mn sources for such uses. Inactive sources prepared under suitable experimental parameters characterized by XRD revealed that manganese is deposited in oxide form. SEM and EDS analyses of electrodeposited surfaces confirmed uniform distribution of elements and the absence of fractures, flaws, and spatial variations. Cyclic voltammetry (CV) scans provided information about the electrochemical processes involved in the deposition process. Uniform distribution of radioactivity on surface of source was ascertained by autoradiography. Swipe tests of the encapsulated sources confirmed negligible removable surface contamination. The 54Mn sources containing up to 185KBq of 54Mn on stainless steel discs were prepared. These sources along with other longer lived sources were supplied to various users as a package of radiation sources for characterization of gamma counting systems over a wide energy range.

Dose-dependent cell cycle arrest and apoptosis in HER2 breast cancer cells by177Lu-CHX-A"-DTPA-Trastuzumab.

BACKGROUND: Trastuzumab is a Food and Drug Administration-approved humanized monoclonal antibody which targets the extracellular domain of human epidermal growth factor receptor 2 (HER2) receptor overexpressed on HER2-positive breast cancer cells. The combination of Lutetium-177 (177 Lu) (t½= 6.7 days, Eßmax497 keV (78.6%) and trastuzumab makes it a suitable targeting agent for radioimmunotherapy. In preclinical and clinical studies,177 Lu-Trastuzumab has proven to be effective for the treatment of HER2-positive malignancies such as breast and ovarian cancer. OBJECTIVES: In this study, we report the mechanism of action of177 Lu-CHX-A"-diethylenetriaminepentaacetic acid (DTPA)-trastuzumab at the cellular and molecular level by performing various in vitro assays in HER2-positive MDA-MB-453 breast cancer cells. MATERIALS AND METHODS: Trastuzumab was conjugated to the bifunctional chelating agent (BFCA) para-isothiocyanatobenzyl-DTPA and radiolabeled with177 Lu. In vitro cell binding studies were carried out in MDA-MB-453 cells to confirm the specificity of the complex toward the receptor. Cellular toxicity, cell cycle, and cell death analysis were also performed for exploring the potential of the radioimmunoconjugate at cellular and molecular level. RESULTS: In vitro cell binding studies showed a maximum binding of 10.7 ± 0.1% which reduced to 2.9 ± 0.1% on coincubation with unlabeled antibody. Our study revealed that the cellular toxicity was dose dependent, and mode of cell death was predominantly by apoptosis. The radioimmunoconjugate retarded the cell in the S phase of cell cycle with two-fold increase in G2/M arrest which justifies the enhanced apoptosis at higher doses. CONCLUSIONS: The study revealed that the formulation can execute a dose-dependent cellular toxicity through induction of apoptosis.

Bioevaluation of (90)Y-labeled particles in animal model of arthritis.

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.

Accumulation of heavy metals in dietary vegetables and cultivated soil horizon in organic farming system in relation to atmospheric deposition in a seasonally dry tropical region of India.

Increasing consciousness about future sustainable agriculture and hazard free food production has lead organic farming to be a globally emerging alternative farm practice. We investigated the accumulation of air-borne heavy metals in edible parts of vegetables and in cultivated soil horizon in organic farming system in a low rain fall tropical region of India. The factorial design of whole experiment consisted of six vegetable crops (tomato, egg plant, spinach, amaranthus, carrot and radish) x two treatments (organic farming in open field and organic farming in glasshouse (OFG)) x seven independent harvest of each crop. The results indicated that except for Pb, atmospheric deposition of heavy metals increased consistently on time scale. Concentrations of heavy metals in cultivated soil horizon and in edible parts of open field grown vegetables increased over time and were significantly higher than those recorded in OFG plots. Increased contents of heavy metals in open field altered soil porosity, bulk density, water holding capacity, microbial biomass carbon, substrate-induced respiration, alkaline phosphatase and fluorescein diacetate hydrolytic activities. Vegetable concentrations of heavy metal appeared in the order Zn > Pb > Cu > Ni > Cd and were maximum in leaves (spinach and amaranths) followed by fruits (tomato and egg plant) and minimum in roots (carrot and radish). Multiple regression analysis indicated that the major contribution of most heavy metals to vegetable leaves was from atmosphere. For roots however, soil appeared to be equally important. The study suggests that if the present trend of atmospheric deposition is continued, it will lead to a destabilizing effect on this sustainable agricultural practice and will increase the dietary intake of toxic metals.