Anti-proliferative effect and underlying mechanism of ethoxy-substituted phylloquinone (vitamin K1 derivative) from Spinacia oleracea leaf and enhancement of its extractability using radiation technology.

In our previous studies, a novel antimutagenic compound, 2-ethoxy-3-(3,7,11,15-tetramethylhexadec-2-ethyl) naphthaquinone-1,4-dione (ethoxy-substituted phylloquinone; ESP) from spinach was characterized and mechanism contributing to its antimutagenicity was deduced. In the current study, anti-proliferative activity of ESP was assessed in lung cancer (A549) cells using MTT [3-(4,5-dimethylthiazole-2yl)-2,5-diphenyl tetrazolium bromide], clonogenic assays and cell cycle analysis. ESP treatment showed selective cytotoxicity against lung cancer cells and no cytotoxicity in normal lung (WI38) cells. Cell cycle analysis revealed that ESP treatment arrests A549 cell population in G2-M phase. In-silico analysis indicated positive drug-likeness features of ESP. Molecular docking showed H-bonding and hydrophobic interactions between ESP and B-DNA dodecamer residues at minor groove. SWATH-MS (Sequential Window Acquisition of All Theoretical Mass Spectra) based proteomic analysis indicated down-regulation of proteins involved in EGFR signaling, NEDDylation and other metabolic pathways and up-regulation of tumor suppressor (STAT1 and NDRG1) proteins. Treatment of spinach powder with gamma radiation (5-20 kGy) from cobalt (Co-60) enhanced the extractability of ESP up to 4.4-fold at the highest dose of 20 kGy. Scanning electron microscopy of spinach powder displayed decrease in smoothness and compactness with increase in radiation dose attributing to its enhanced extractability. Increase in the extractability of ESP with increasing radiation doses as measured by fluorescence intensity and dry weight basis was strongly correlated. Nonetheless, radiation treatment did not affect the functionality of ESP in terms of anti-proliferative and antimutagenic activities. Current findings thus highlight broad spectrum bioactivity of ESP from spinach, its underlying mechanism and applicability of radiation technology in enhancing extractability. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03264-6.

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.

Utilization of Chemical Deposition Technique for Preparation of Miniature 170Tm Sources and Preliminary Quality Assessment for Potential Use in Brachytherapy.

OBJECTIVE: This article describes the preparation of a 170Tm source by chemical deposition technique, its encapsulation in a titanium holder, and preliminary quality evaluation for potential utility as a brachytherapy source. METHODS: The procedure consisted of electrodeposition of Ni on a Cu wire followed by chemical deposition of 170Tm on it. Influence of feed solution pH, carrier Tm concentration, and reaction time were studied for optimum deposition of 170Tm on substrate. After sealing the source core in a titanium capsule, quality control tests were performed. Distribution of 170Tm on substrate was evaluated by autoradiography. Inactive Tm source was characterized by scanning electron microscope (SEM) and energy-dispersive X-ray (EDS) analyses. RESULTS: Under optimized conditions (pH 5, 10 µg Tm carrier, 5 h), 170Tm source core could be prepared by deposition of >95% of 170Tm radioactivity on substrate. Swipe tests and immersion tests on encapsulated sources confirmed that removable radioactivity and radioactivity leakage levels were within stipulated limits. Autoradiography of 170Tm source confirmed uniformity of radioactivity distribution. While SEM analysis confirmed good adhesion of Tm on substrate, EDS analysis confirmed elemental constituents of the Tm-deposited substrate. CONCLUSION: The objective of preparing a 170Tm source by chemical deposition for potential brachytherapy applications could be successfully achieved.

Hydroxyapatite (HA) microparticles labeled with (32)P - A promising option in the radiation synovectomy for inflamed joints.

In the present article we describe a systematic approach pursued for the synthesis of (32)P-labeled hydroxyapatite (HA) microparticles (1-10µm size range) using no carrier added (NCA) (32)P produced in a nuclear reactor and animal evaluation of its utility as an expected viable radiopharmaceutical for the treatment of pain intensive arthrosis. NCA (32)P was produced via the (32)S(n,p)(32)P route in nuclear reactor with high radionuclidic purity (99.95±0.01%, n=5). Phosphorus-32-labeled hydroxyapatite microparticles (1-10µm size range) were synthesized with high radiochemical purity (99.0±0.3% n=12) under optimized conditions and the formulation showed excellent in vitro stability in saline as well as in rat serum. Intra-articular administration of the radiolabeled particles in the knee joints of normal Wistar rats showed near-complete retention of activity within the synovial cavity upto 1 month post-administration. The radiochemical formulation thus demonstrated promising features as a radiopharmaceutical for treatment of arthritis with excellent logistic advantage for shipment to sites distant from the production facility thanks to the suitable nuclear decay properties of (32)P.

Studies on the development of ¹69Yb-brachytherapy seeds: New generation brachytherapy sources for the management of cancer.

This paper describes development of (169)Yb-seeds by encapsulating 0.6-0.65 mm (ϕ) sized (169)Yb2O3 microspheres in titanium capsules. Microspheres synthesized by a sol-gel route were characterized by XRD, SEM/EDS and ICP-AES. Optimization of neutron irradiation was accomplished and (169)Yb-seeds up to 74 MBq of (169)Yb could be produced from natural Yb2O3 microspheres, which have the potential for use in prostate brachytherapy. A protocol to prepare (169)Yb-brachytherapy sources (2.96-3.7 TBq of (169)Yb) with the use of enriched targets was also formulated.

Radiochemistry, pre-clinical studies and first clinical investigation of 90Y-labeled hydroxyapatite (HA) particles prepared utilizing 90Y produced by (n,γ) route.

INTRODUCTION: The scope of using no carrier added (NCA) (90)Y [T(1/2) = 64.1 h, Eß(max) = 2.28 MeV] obtained from (90)Sr/(90)Y generator in radiation synovectomy (RSV) is widely accepted. In the present study, the prospect of using (90)Y produced by (n,γ) route in a medium flux research reactor for use in RSV was explored. METHODS: Yttrium-90 was produced by thermal neutron irradiation of Y(2)O(3) target at a neutron flux of ~1×10(14) n/cm(2).s for 14 d. The influence of various experimental parameters were systematically investigated and optimized to arrive at the most favorable conditions for the formulation of (90)Y labeled hydroxyapatite (HA) using HA particles of 1-10 µm size range. An optimized kit formulation strategy was developed for convenient one-step compounding of (90)Y-HA, which is easily adaptable at hospital radiopharmacy. The pre-clinical biological evaluation of (90)Y-HA particles was studied by carrying out biodistribution and bioluminiscence imaging studies in Wistar rats. The first clinical investigation using the radiolabeled preparation was performed on a patient suffering from chronic arthritis in knee joint by administering 185 MBq (90)Y-HA formulated at the hospital radiopharmacy deploying the proposed strategy. RESULTS: Yttrium-90 was produced with a specific activity of 851 ± 111 MBq/mg and radionuclidic purity of 99.95 ± 0.02%. (90)Y-labeled HA particles (185 ± 10 MBq doses) were formulated in high radiochemical purity (>99%) and excellent in vitro stability. The preparation showed promising results in pre-clinical studies carried out in Wistar rats. The preliminary results of the first clinical investigation of (90)Y-HA preparation in a patient with rheumatoid arthritis in knee joints demonstrated the effectiveness of the formulation prepared using (90)Y produced via (n,γ) route in the management of the disease. CONCLUSION: The studies revealed that effective utilization of (90)Y produced via (n,γ) route in a medium flux research reactor coupled with the developed strategy of using HA kits for convenient formulation of (90)Y-HA at the hospital radiopharmacy can contribute to sustainable growth in the clinical utilization of (90)Y in RSV in the foreseeable future.

Lanthanide-ion-assisted structural collapse of layered GaOOH lattice.

GaOOH nanorods were prepared by hydrolysis of Ga(NO(3))(3)·xH(2)O by urea at ~100 °C in the presence of different amounts of lanthanide ions like Eu(3+), Tb(3+), and Dy(3+). On the basis of X-ray diffraction and vibrational studies, it is confirmed that layered structure of GaOOH collapses even when very small amounts of lanthanide ions (1 atom % and more) are present in the reaction medium during the synthesis of GaOOH nanorods. The incorporation of lanthanide ions at the interlayer spacing of the GaOOH lattice, followed by its reaction with OH groups that connect the layers containing edge-shared GaO(6) in GaOOH, is the reason for the collapse of the layered structure and associated amorphization. This leads to the formation of finely mixed hydroxides of lanthanide and gallium ions. These results are further confirmed by steady-state luminescence and excited-state lifetime measurements carried out on the samples. The morphology of the nanorods is maintained upon heat treatment at high temperatures like 500 and 900 °C, and during this process, the finely mixed lanthanide and gallium hydroxides facilitate diffusion of lanthanide ions into the Ga(2)O(3) lattice, as revealed by the existence of strong energy transfer with an efficiency of more than 90% between the host and lanthanide ions.