Immune response against antigens irradiated with 60Co gamma-rays

Summary In the present work, we investigated the immunological behavior of bothropstoxin-1, a K49 phospholipase from Bothrops jararacussu, and of ovalbumin before and after irradiation with ⁶⁰Co g-rays. Isogenic mice were immunized with either native or irradiated proteins. The circulating antibodies were isotyped and titrated by ELISA. Results indicate that irradiated proteins were immunogenic and the antibodies elicited by them were able to recognize the native proteins in ELISA. Data also indicate that the irradiated protein induced higher titers of IgG2a and IgG2b, suggesting that Th1 cells were predominantly involved in the immune response. Structural modifications of the proteins were investigated by SDS-PAGE, mass spectrometry and size exclusion chromatography. According to our data, irradiation promoted structural modifications on both proteins, characterized by higher molecular weight forms (aggregates and oligomers). When analyzed by mass spectrometry, the irradiated bothropstoxin appeared in several oxidized forms. These results indicate that irradiation of toxic proteins can promote significant modifications in their structures, but still retain many of the original antigenic and immunological properties of native form.     

Structure alteration and immunological properties of 60Co-gamma-rays irradiated bothropstoxin-I

In this work, the authors investigated the immunological behavior of bothropstoxin-I (BTHX-1), before and after irradiation process, and also the influence of scavengers substances on protein alterations induced by free radical production. Structural modifications were investigated by SDS-PAGE in reducing or non-reducing conditions. In vitro cytotoxicity assay was performed to test average toxic activities of BTHX-I. BALB/c Isogenic mice were immunized with irradiated or non-irradiated (native) forms of BTHX-I and antibody titers and isotypes were determined by ELISA method. Expression of murine cytokines was analyzed by using expression data obtained by quantitative real-time PCR (qPCR) assays. The results indicate that irradiation of proteins leads to significant structural modifications, and also changes the cytokines profile during immunization process, regarding a suitable approach to new immunogenic production.     

Preparation of <Superscript>95m</Superscript>Tc radiotracer

Several procedures for preparation of the ^95mTc radiotracer following irradiation of a thin Mo target with deuterons were tested. The procedures consisting of alkaline-oxidative fusion of the irradiated target in a mixture of Na₂O₂ + NaOH and subsequent liquid–liquid extraction with 2-butanone, and acid decomposition of the target in a mixture of H₂SO₄ + HNO₃ followed by extraction chromatography with PAN-Aliquat 336 composite material appeared suitable for the given purpose.     

A comparative study on the separation of radioyttrium from Sr- and Rb-targets via ion-exchange and solvent extraction techniques,with special reference to the production of no-carrier-added <Superscript>86</Superscript>Y, <Superscript>87</Superscript>Y and <Superscript>88</Superscript>Y using a cyclotron

The radiochemical separation of ⁸⁸Y from proton irradiated ^natSrCO₃ and alpha-particle irradiated ^natRbCl, of ⁸⁶Y from proton irradiated ⁸⁶SrCO₃, and of ⁸⁷Y from alpha-particle irradiated ^natRbCl were studied at no-carrier-added levels by two techniques, namely, ion-exchange chromatography using Dowex 50W-X8 and Dowex 21K resins, and solvent extraction using HDEHP. Out of all those methods, the ion-exchange chromatography using Dowex 50W-X8 (cation-exchanger) was found to be the best: the separation yield was high, the chemical impurity in the separated radioyttrium (inactive Sr or Rb) was low (0.5 μg) and the final product was obtained in the form of citrate. The optimized separation method using Dowex 50W-X8 was applied in practical production of ⁸⁶Y and ⁸⁸Y via proton irradiations of ⁸⁶SrCO₃ and ^natSrCO₃, respectively, at 16 MeV as well as of ⁸⁷Y and ⁸⁸Y via α-particle irradiation of ^natRbCl at 26 MeV. The tangible experimental yields of ⁸⁶Y and ⁸⁷Y amounted to 150 and 5.7 MBq/μA·h, respectively. The yields of ⁸⁸Y obtained were 0.06 MBq/μA·h and 1 MBq/μA·h for alpha-particle and proton irradiations, respectively. Each yield value corresponds to more than 70% of the respective theoretical value.     

Separation of <Superscript>139</Superscript>Ce using solvent extraction technique from La<Subscript>2</Subscript>O<Subscript>3</Subscript> target irradiated by 14.7 MeV protons

The radiochemical separation of no-carrier-added cerium from proton irradiated lanthanum was studied by solvent extraction using DEE, TBP and TPPO, the latter reagent being employed for the first time for separation of radiocerium from bulk of lanthanum. Distribution coefficients of cerium and lanthanum were investigated as a function of equilibrium time and concentration of HNO₃. A mixture of 0.05M K₂Cr₂O₇ and 0.1M H₂SO₄ was used as an oxidizing agent to improve the separation efficiency of cerium. A comparative study of the three extractants released that DEE is the best for separation of cerium from bulk of lanthanum oxide. The target was prepared by pressing. The production of ¹³⁹Ce of high radionuclidic purity and chemical purity via irradiation of lanthanum oxide target at MGC-20 cyclotron with protons of energy 14.5 MeV is described. The experimental yield was found to be 153 kBq/μA·h.     

A comparison of modifications induced by Li<Superscript>3+</Superscript> and Ag<Superscript>8+</Superscript> ion beams irradiation in poly(lactide-<Emphasis Type="Italic">co</Emphasis>-glycolide) films

Poly(lactide-co-glycolide) (PLGA) films were irradiated by 180 MeV/amu Ag⁸⁺ ions and 50 MeV/amu Li³⁺ ions at different fluences of 5 × 10¹⁰, 5 × 10¹¹ and 1 × 10¹² ions/cm². Modifications of polymer films induced by the swift heavy ions (SHI) irradiation were studied by X-ray diffraction (XRD), Field emission scanning electron microscopy (FESEM), Fourier transform infrared spectroscopy (FTIR) and UV–Vis spectroscopy. The dominant effect of the SHI beam irradiation is proposed to be chain scission which leads to breakage of polymer chains, followed by hydrogen abstraction. The results from FTIR spectroscopy showed that the intensity of all peaks of the irradiated samples decreased at high fluence of SHI, suggesting PLGA samples significantly degraded at high SHI fluence. The variation in optical band gap energy and Urbach energy with increasing fluence was calculated from UV–Vis spectroscopy and explained in terms of changes occurring in the polymer matrix. X-ray diffraction patterns also show appreciable changes in PLGA at high fluence. FESEM results revealed that the hydrophilicity of the PLGA surface increased with an increase in ion fluence. In this paper the optical, chemical and structural changes with different fluence rates are discussed.     

Porous ZrC-carbon microspheres as potential insoluble target matrices for production of <Superscript>188</Superscript>W/<Superscript>188</Superscript>Re

New microsphere sorbents are reported, which could find application in demanding radiation environments and especially as targets for the production of nuclear medicines by neutron irradiation. An easily-synthesized Zr anionic complex was introduced into quaternary amine-functionalised polystyrene-divinylbenzene-based anion-exchange resins by batch adsorption. Upon carbothermal reduction, the precursors were converted to porous carbon matrices containing particles of ZrC and ZrO₂ polymorphs. The most phase-pure material, ZrAX-1, possessed high surface area, multi-scale porosity and high mechanical strength. Adsorption of Re and W was investigated and its possible deployment as a reusable host for the production of ¹⁸⁸W/¹⁸⁸Re is discussed.     

Pyridyl derivatives provide new pathways for labeling protein with fac-[<Superscript>188</Superscript>Re(CO)<Subscript>3</Subscript>(H<Subscript>2</Subscript>O)<Subscript>3</Subscript>]<Superscript>+</Superscript>

The purpose of this work was to indirect label IgG with fac-[¹⁸⁸Re(CO)₃(H₂O)₃]⁺ and to check the radiochemical behavior of the labeled product. The compound of (bis(2-pyridylmethyl)-amino)-acetic acid (L²H) was synthesized and labeled with fac-[¹⁸⁸Re(CO)₃(H₂O)₃]⁺. The labeling yield of ¹⁸⁸Re(CO)₃–L²H was more than 90%. The effects of protein concentration, reaction time, pH and reaction temperature of labeling of IgG with ¹⁸⁸Re(CO)₃–L²H were investigated. The conjugation conditions were optimized. The labeled product was analyzed by size exclusion HPLC and TLC. The stability of ¹⁸⁸Re(CO)₃–L²H–IgG in vitro was high. The results of this study may be useful for [¹⁸⁸Re(CO)₃(H₂O)₃]⁺ labeling of protein for radioimmunotherapy.     

Atmospheric depositional fluxes of cosmogenic <Superscript>32</Superscript>P, <Superscript>33</Superscript>P and <Superscript>7</Superscript>Be in the Sevastopol region

⁹⁰Y was separated from ⁹⁰Sr using an extraction chromatographic resin consisting of 4, 4′(5′)-bis-t-butylcyclohexano-18-crown-6 (DtBuCH₁₈C₆), 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl) amide (C₂mimNTf₂), and a polymer (Amberlite XAD-7). Ionic liquid was introduced into the column to improve the separation efficiency. The column showed an excellent performance for the separation of Y from Sr. After the separation, the ratio of ⁹⁰Sr/⁹⁰Y was <2.0 × 10^?5; the column was recycled for >18 times. This study provides preliminary results on columns to produce ⁹⁰Y with a high purity in radiopharmaceuticals.     

Extraction of metal ions (Fe<Superscript>3+</Superscript>, Co<Superscript>2+</Superscript>, Ni<Superscript>2+</Superscript>, Cu<Superscript>2+</Superscript> and Zn<Superscript>2+</Superscript>) using immobilized-polysiloxane iminobis(n-2-aminophenylacetamide) ligand system

A new insoluble solid functionalized ligand system bearing chelating ligand group of the general formula P-(CH₂)₃-N[CH₂CONH(C₆H₄)NH₂]₂, where P represents [Si–O] _n polysiloxane network, was prepared by the reaction of the immobilized diethyliminodiacetate polysiloxane ligand system, P-(CH₂)₃N(CH₂CO₂Et)₂ with 1,2-diaminobenzene in toluene. ¹³C CP-MAS NMR, XPS and FTIR results showed that most ethylacetate groups (–COOEt) were converted into the amide groups (–N–C=O). The new functionalized ligand system exhibits high capacity for extraction and removal of the metal ions (Fe³⁺, Co²⁺, Ni²⁺, Cu²⁺ and Zn²⁺) with efficiency of 95–97% after recovery from its primary metal complexes. This functionalized ligand system formed 1:1 metal to ligand complexes.     

Production and chemical separation of <Superscript>48</Superscript>V

Summary Vanadium-48 was produced with an activity of 222 MBq (6 mCi) by the ^natTi(d,xn)⁴⁸V nuclear reactions in the U-120 cyclotron. The energy of the irradiating beam was 13 MeV, its intensity 5 μA, and the metallic Ti target dimension 11’11 mm² (0.1 mm thickness). For target cooling, circulated water in target backside was used. After 3 cooling days, only ⁴⁸V and some ⁴⁶Sc (T_1/2 = 83.8 d), produced by the side nuclear reaction ⁴⁸Ti(d,α)⁴⁶Sc were found in the target. For production of the radiotracer of ⁴⁸V and for the preparation of source for standardization of ⁴⁸V by 4πβ-γ coincidence, the Ti target was dissolved either in HF or in H₂SO₄. For both dissolving methods an ion-exchange separation procedure was developed.     

Separation of radioarsenic from irradiated germanium oxide targets for the production of <Superscript>71</Superscript>As and <Superscript>72</Superscript>As

A method for the separation of no-carrier-added arsenic radionuclides from the bulk amount of proton-irradiated GeO₂ targets as well as from coproduced radiogallium was developed. The radionuclides ⁶⁹Ge and ⁶⁷Ga produced during irradiation of GeO₂ were used as tracers for Ge and Ga in the experiments. After dissolution of the target the ratio of As(III) to As(V) was determined via thin layer chromatography (TLC). The extraction of radioarsenic by different organic solvents from acid solutions containing alkali iodide was studied and optimized. The influence of the concentration of various acids (HCl, HClO₄, HNO₃, HBr, H₂SO₄) as well as of KI was studied using cyclohexane. The optimum separation of radioarsenic was achieved using cyclohexane with 4.75 M HCl and 0.5 M KI and its back-extraction with a 0.1% H₂O₂ solution. The separation leads to high purity radioarsenic containing no radiogallium and <0.001% [⁶⁹Ge]Ge. The overall radiochemical yield is 93 ± 3%. The practical application of the optimized procedure in the production of ⁷¹As and ⁷²As is demonstrated and batch yields achieved were in the range of 75–84% of the theoretical values.     

Synthesis,scope, <Superscript>1</Superscript>H and <Superscript>13</Superscript>C spectral assignments of isomeric dibenzofuran carboxaldehydes

Two isomeric dibenzofuran carboxaldehydes, namely 2-methoxydibenzo[b,d]furan-1-carbaldehyde (4) and 2-methoxydibenzo[b,d]furan-3-carbaldehyde (5), were synthesized. Formylation of 2-methoxydibenzo[b,d]furan (3) with α,α-dichloromethyl methyl ether and tin(IV) chloride gave a mixture of aldehydes 4 and 5 in 95 % yield and in a 35:65 ratio. Their ¹H and ¹³C NMR spectral signals were not sufficiently resolved in CDCl₃ solution to achieve their complete assignment, but this was possible in DMSO-d ₆ with the help of 2D-NMR techniques: NOESY for ¹H–¹H interactions and HSQC and HMQC experiments for ¹H–¹³C correlations. These aldehydes were used in the synthesis of novel β-phenylethylamines and NBOMe derivatives, which are undergoing biological evaluation.     

Production of <Superscript>122</Superscript>Sb for the study of environmental pollution

This article presents, ¹²²Sb (T _1/2 = 2.723 days, I _β- = 97.59%) was produced via the ^natSn(p,xn) nuclear process at the AMIRS (Cyclone-30, IBA, Belgium). The electrodeposition experiments were carried out by potassium stannate trihydrate (K₂Sn(OH)₆) and potassium hydroxide. The optimum conditions of the electrodeposition of tin were as follows: 40 g/L ^natSn, 20 g/L KOH, 115 g/L K₂Sn(OH)₆, DC current density of 5 A/dm² with a bath temperature of 75 °C. The electroplated Tin-target was irradiated with 26.5 MeV protons at current of 180 μA for 20 min. Solvent extraction of no-carrier-added ¹²²Sb from irradiated Tin-natural target hydrochloric solution was investigated using di-n-butyl ether (C₈H₁₈O). Yields of about 3.61 MBq/μAh were experimentally obtained.     

PC-controlled radiochemistry system for preparation of no-carrier-added <Superscript>64</Superscript>Cu

A homemade modular PC-controlled radiochemistry system, used to separate the no-carrier-added ⁶⁴Cu from irradiated electroplated solid cyclotron target ⁶⁴Ni layers was developed. Upon irradiation the target layer is dissolved in diluted nitric acid, followed by selective liquid–liquid extraction of the ⁶⁴Cu. The final purification step is achieved making use of an anion exchange column. All the separation procedures can be carried out remote-controlled with a minimized risk of operator errors within less than 2 h, with excellent processing yield (>95%).     

Preparation of <Superscript>26</Superscript>Al, <Superscript>59</Superscript>Ni, <Superscript>44</Superscript>Ti, <Superscript>53</Superscript>Mn and <Superscript>60</Superscript>Fe from a proton irradiated copper beam dump

The station for pions cancer therapy was operated at PSI from 1980 to 1992. After a cooling time of 12 years it’s made of copper beam dump was cut and samples were taken for analytical purposes. The sampling collected about 500 g of high active copper chips that can be used for separation of exotic radionuclides. The analyses by gamma spectrometry, LSC and AMS showed main nuclides present to be ⁶⁰Co, ⁵⁴Mn, ²²Na, ⁶⁵Zn, ²⁶Al, ⁵³Mn, ⁵⁹Ni, ⁶³Ni, ⁵⁵Fe and ⁶⁰Fe and ⁴⁴Ti with a daughter nuclide ⁴⁴Sc. In the frame of ERAWAST project a procedure combining selective precipitation and ion exchange for the separation of the rare radionuclides from the copper beam dump was developed. The proposed separation procedure is easy for remote controlled implementation in a hot cell. The ion exchange separation of Ni, Al, Mg, Ti and Fe was complete and high decontamination factors for copper and cobalt were achieved. Based on the developed procedure a remotely controlled system for separation of exotic radionuclides from the copper chips was set up. The full scale system was installed in a hot cell where high activity levels can be handled. In order to evaluate the reliability and functionality of the system extensive tests have been done. During the test period 13.86 g in total of the proton irradiated copper beam dump were processed for separation of ²⁶Al, ⁵⁹Ni, ⁵³Mn, ⁴⁴Ti and ⁶⁰Fe. The results showed that the system was operational and the radionuclide separation was selective with high chemical yield. The procedure manages as well the generated liquid wastes containing high level of ⁶⁰Co activity.     

Industrial production and purification of <Superscript>32</Superscript>P by sulfur irradiation with partially moderated neutron fluxes and target melting

Target purification of S_α is carried out by distillation at 444±2 °C under N atmosphere and diluting the vapors in CS₂. The solution is filtered through fiberglass, Teflon and cellulose to obtain S_α by CS₂ evaporation. Once 30 g of this target are irradiated with fast neutron fluxes from 4.5 to 7.4·10¹² n·cm⁻²s⁻¹ from 6 to 12 hours, the nuclear reaction ³²S(n,p)³²P takes place. So, the irradiated S_α sample is placed in a Pyrex container situated inside a furnace as the most important piece of equipment in one aluminum and Lucite glove box. The distillation of irradiated sulfur takes place at 444±2 °C under N atmosphere during 1–2 hours. The vapors are connected to a sulfur diluter containing 20% CS₂ aqueous solution, followed by an activated carbon filter and the two similar additional sulfur diluters. Once cooled, the distillation chamber keeps the radioactive, carrier-free ³²P stuck to the wall. Then 25–50 ml of 0.1N HCl acid was injected by suction and heated again at 110±2 °C during 1 hour. The corresponding chemical reaction takes place and the labeled H₃ ³²PO₄ solution is produced. In such a way, industrial production of ³²P labeled molecules has started in Mexico, with an initial production of 3700–5550 MBq per week.     

Photocatalytic degradation of adenosine triphosphate in an aqueous suspension of TiO<Subscript>2</Subscript>: a HPLC and <Superscript>1</Superscript>H-NMR study

Photocatalytic degradation process of ATP was followed by HPLC and ¹H-NMR measurements. Adenine was one of the major products when the aqueous ATP sample with TiO₂ dispersion was irradiated by UV light (λ = 365 nm) for 90 min. The ¹H-NMR spectra indicated the presence of another product (Z), which likely came from the ribose moiety in ATP. Photocatalytic generation of OH^˙ radicals on TiO₂ surface was concluded to be responsible for degrading ATP. A working hypothesis of the reaction process was proposed to account for the reaction products.     

Synthesis,characterisation and photocatalytic activity of Ag<Superscript>+</Superscript>- and Sn<Superscript>2+</Superscript>-substituted KSbTeO<Subscript>6</Subscript>

Ag⁺- and Sn²⁺-substituted KSbTeO₆ were prepared by a facile ion-exchange method at ambient temperature. All the samples were characterised by scanning electron microscopy, energy-dispersive spectra, thermogravimetric analysis, powder X-ray diffraction, Raman spectra and UV-VIS diffuse reflectance spectra. Both Sn²⁺- and Ag⁺-substituted KSbTeO₆ were crystallised in a cubic lattice with the \(Fd\bar 3m\) space group. The band-gap energy of all the samples was deduced from their UV-VIS diffuse reflectance spectral profiles. The visible light-induced photocatalytic oxidation of the methylene blue (MB) dye was examined in the presence of all the as-prepared materials. The Ag⁺- and Sn²⁺-substituted KSbTeO₆ exhibited a higher photocatalytic activity than the parent KSbTeO₆ in degradation of the MB dye under visible light irradiation.     

Study of the cyclotron production of <Superscript>172</Superscript>Lu: an excellent radiotracer

¹⁷²Lu due to its suitable (T _1/2 = 6.7 days) and high detection sensitivity, is used as a radiotracer in different fields. ¹⁷²Lu appears to be suitable as a long-lived rare-earth tracer for compound labelling and biodistribution studies. In the present study, excitation functions via ¹⁷²Yb(p,n)¹⁷²Lu, ^natYb(p,xn)¹⁷²Lu, ¹⁷²Yb(d,2n)¹⁷²Lu and ^natYb(d,xn)¹⁷²Lu reactions were calculated by ALICE/91, ALICE/ASH and TALYS-1.2 codes. Deposition of ^natYb₂O₃ on Cu substrate was carried out via sedimentation method for the production of ¹⁷²Lu. Cementation separation process and liquid–liquid extraction (LLX) of no-carrier-added (nca) radiolutetium from irradiated ytterbium(III)oxide target hydrochloric solution was described using Na(Hg) amalgam, α-hydroxyisobutyric acid (α-HIB) and di-(2-ethylhexyl)phosphoric acid (HDEHP).