A 228Ra-212Pb tandem generator for potential application in biomedical studies

A new tandem generator system (cation-exchange generator column coupled to anion-exchange), based on the ²²⁸Ra as starting radionuclide, for ²¹²Pb/²¹²Bi production in the solutions suitable to direct application in biomedical investigations has been developed. Optimum conditions have been found for retention of Ra, Th and Ac parent radionuclides on the cation-exchange column and repeated elution of Pb with subsequent concentration on anion-exchange column using HBr and mixed HBr/CH₃OH solutions. It was shown that Pb/Bi could be eluted from anion — exchange column with a small volume of EDTA, DTPA, NaCl solutions or heated H₂O. The advantages of the tandem generator system for production of short-lived Pb/Bi radionuclides and their application for biomedical studies are discussed.     

Rapid separation of212Pb−212Bi−208Tl by high-performance liquid ion chromatography

Fast radiochemical separation of carrier-free²¹²Pb–²¹²Bi–²⁰⁸Tl in radioactive equilibrium was performed using the HPLC technique with an ion-exchange column /ION-210 for cation exchange, ION-110 for anion exchange and C18 loaded with cation-exchange sites/. Optimal results are obtained with the ION-110 column.²⁰⁸Tl and²¹²Pb are eluted by 0.5M HCl in 2.5 and 5 min, respectively.²¹²Bi is recovered by elution with 1M HNO₃.     

Search of ligands suitable for 212Pb/212Bi in vivo generators

The short half-life of ²¹²Bi and ²¹³Bi limits the application of these radionuclides in α radionuclide therapy. The labeling of biomolecules with ²¹²Pb (mother nuclide of ²¹²Bi) instead of ²¹²Bi or ²¹³Bi has the advantage of obtaining a conjugate with a half-life of 10.6 h, compared with of 60 min for ²¹²Bi or 46 min for ²¹³Bi. Previous attempts to prepare a potential in vivo generator with ²¹²Pb complexed by the DOTA chelator failed, because about 36 % of Bi was reported to escape as a result of the radioactive decay $^{{212}}{\text{Pb}}{\mathop{\longrightarrow}\limits^{\beta ^{ - }}}{^{212}{\text{Bi}}}$ . Herein, we report studies on the stability of the ²¹²Pb complexes with eight selected polydentate ligands, which demonstrate high affinity for 3+ metal cations. From the ligand studied DOTP and BAPTA show a sufficient ²¹²Pb labeling yields but only ²¹²Pb–DOTP complex is stable in isotonic solution of sodium chloride making this way radioactivity level of released ²¹²Bi is below the limit of detection. It should be emphasized that the DOTP complex is stable only in the case when the concentration of free DOTP exceeds 10^?4 M.     

Separation of zirconium and hafnium from early actinides and rare earth elements with eichrom’s pb resin in HCl

The separation of zirconium and hafnium isotopes from the early actinides and rare earth elements (REE) with Eichrom’s Pb resin has been studied. Batch studies were performed to characterize the behavior of actinium, thorium, zirconium, hafnium, lutetium, and yttrium on Pb resin from HCl solutions (0.001 M to 11 M). The early actinides and REE had no affinity for the resin at any concentration of HCl, but zirconium and hafnium showed a moderate uptake at high concentrations of HCl with a maximum extraction at 11 M HCl. Several column separations were tested, including with only tracer isotopes and with mass. Rapid, simple separations of zirconium from actinium, thorium, protactinium, and the REE with high yields and low elution volumes are presented with applications for tracer isotope production and fission product separations. The resin is less suitable for hafnium separations as hafnium tends to bleed off the resin even at high concentrations of HCl.

     

<Superscript>137</Superscript>Cs/<Superscript>137m</Superscript>Ba radioisotope generator based on 6-tungstocerate(IV) column matrix

Summary Barium-137m radioisotope generator of the chromatographic column elution mode based on loading 1.5 g 6-tungstocerate(IV) gel matrix with ~54 kBq of fission-produced ¹³⁷Cs is described. The elution performance of the generated ^137mBa radionuclide was investigated as a function of chemical composition of the eluent, flow rate, elution frequency, and age of the generator system. At comparable conditions, ^137mBa eluates with 0.9% NaCl-0.1M HCl eluent had higher elution yields and radionuclidic purity than with 0.1M NH₄Cl-0.1M HCl eluent. The generator has been repeatedly eluted for 311 days by passing 4810 ml of the saline eluent (10 ml × 481 elution operations) at a flow rate of 3.0 ml/min. Barium-137m eluates of high and reproducible elution yields, chemical and radionuclidic purities of (≥ 99.99%) were obtained.     

Time sequence determination of parent–daughter radionuclides using gamma-spectrometry

The acquisition of time-stamped list data provides additional information useful to gamma-spectrometry analysis. A novel technique is described that uses non-linear least-squares fitting and the Levenberg–Marquardt algorithm to simultaneously determine parent-daughter atoms from time sequence measurements of only the daughter radionuclide. This has been demonstrated for the radioactive decay of short-lived radon progeny (²¹⁴Pb/²¹⁴Bi, ²¹²Pb/²¹²Bi) described using the Bateman first-order differential equation. The calculated atoms are in excellent agreement with measured atoms, with a difference of 1.3–4.8% for parent atoms and 2.4–10.4% for daughter atoms. Measurements are also reported with reduced uncertainty. The technique has potential to redefine gamma-spectrometry analysis.

     

210Pb/210Po isotope generator

As a continuation of previous work (Kmak et al. in J Radioanal Nucl Chem 314:985–989, 2017), an isotope generator column based on the ²¹⁰Pb decay chain has been made to produce highly radiopure ²¹⁰Po. Two replicate studies were performed on AG 50Wx8 columns with an average yield of 90.4 ± 1.9%. ²¹⁰Pb breakthrough was seen at the 6 month elution for both generators.

     

Isolation of 212Pb from natural thorium for targeted alpha-therapy

Targeted alpha-therapy (TAT) is increasingly attractive due to its extraordinary antitumor efficacy. However, the supply of α-emitters for TAT is insufficient and under control by a limited number of countries. ²¹²Pb is a promising α-emitter with an optimal half-life (10.6 h) and favored decay chain. Of interest, ²¹²Pb can be extracted directly from natural thorium, which may be abundant in the mining waste of rare-earth, uranium, etc. Indeed, radioactive thorium waste has been a longstanding environmental challenge that needs immediate action. Developing an on-demand and facile process to isolate ²¹²Pb from natural thorium would be ideal to meet the above challenges, yet is difficult. In theory, the ratio of ²¹²Pb to ^natTh is below 10^?13 in commercially available thorium salts. As a pilot study, 2.2 MBq of ²¹²Pb was successfully extracted from a 5 L solution of thorium nitrate by using a Pb-selective resin. The radiochemical purity of ²¹²Pb is over 99.9% according to gamma-ray analysis. The purified ²¹²Pb was applied to radiolabel a couple of peptides used in clinics (i.e. PSMA, TATE and FAPI-04), and the radiochemical yields are >85%. Of note, ²¹²Pb can be repeatedly separated from the thorium solution every 2 days. In summary, a practical and scalable method was developed to isolate ²¹²Pb for potentially clinical use, which may be of great importance as it does not require either cyclotron or nuclear reactor.     

A generator system for production of medical alpha-radionuclides Ac-225 and Bi-213

A generator system, consisting of two anion- and one cation-exchange columns for production of medical α-radionuclides ²²⁵Ac and ²¹³Bi, has been developed. The first anion-exchange column was used for periodical separation of ²²⁵Ac from Th with 8 M HNO₃, while the second anion-exchange column was employed for purification of ²²⁵Ac from Ra and inactive impurities in mixed HNO₃/CH₃OH media. From anion-exchange column ²²⁵Ac was stripped with 0.1–0.2 M HNO₃ and loaded directly onto cation-exchange column, used as a generator for repeated isolation of ²¹³Bi. The cation exchange behavior of Bi and other radionuclides of the interest were studied in diluted HCl, HBr and DTPA solutions used as eluents. As result, a simple and effective method for the production and purification of ²²⁵Ac and ²¹³Bi suitable for biomedical studies was elaborated.     

Radiochemical separation of bismuth activities using Dalzin,and its application to geological problems

A radiochemical method has been devised for the separation of bismuth activities of the natural series,viz.²¹⁴Bi,²¹⁰Bi and²¹²Bi, and applied to the indirect estimation of their corresponding precursors,²²²Rn,²¹⁰Pb and²¹²Pb, in a wide variety of geological materials. The method consists of the solvent extraction of bismuth in radiochemically pure form from the sample solution atpH 2 with diallyldithiocarbamido-hydrazine (Dalzin) in chloroform, and back extraction with 2M acid. The advantages of this method over the dithizone extraction system are discussed.     

Towards translation of 212Pb as a clinical therapeutic; getting the lead in!

Targeted α-particle therapy offers the potential for more specific tumor cell killing with less damage to surrounding normal tissue than β-emitters because of the combination of short path length (50-80 μm) with the high linear energy transfer (100 keV μm(-1)) of this emission. These physical properties offer the real possibility of targeted (pre-targeted) α-therapy suitable for the elimination of minimal residual or micrometastatic disease. Targeted and pre-targeted radioimmunotherapy (RIT) using α-emitters such as (212)Bi (T(1/2) = 1.01 h) and (212)Pb (T(1/2) = 10.6 h) has demonstrated significant utility in both in vitro and in vivo model systems. (212)Pb, a promising α-particle emitting source, is the longer-lived parent nuclide of (212)Bi, and serves as an in vivo generator of (212)Bi. The radionuclide has been successfully used in RIT and pre-targeted RIT and demonstrated an enhanced therapeutic efficacy in combination with chemotherapeutics, such as gemcitabine and paclitaxel. The following perspective addresses the modes of radionuclide production, radiolabelling and chelation chemistry, as well as the application of (212)Pb to targeted and pre-targeted radiation therapy.     

The role of Cherenkov and liquid scintilation counting in evaluating the anion-exchange separation of210Pb−210Bi−210Po

Using as eluent a sequence of 3M HCl, 12M HCl, and 8M HNO₃, a mixture of²¹⁰Pb,²¹⁰Bi, and²¹⁰Po may be clearly separated on a column of Dowex 1×2−100 anion exchange resin. A Cherenkov count in H₂O and the variation in count rate with time confirm that the nuclides emerge in the order²¹⁰Pb→²¹⁰Bi→²¹⁰Po. If 12M HCl is replaced by 1.5M H₂SO₄/2.3 M Na₂SO₄, a clean separation also results, but recovery of²¹⁰Po becomes considerably more difficult. All three nuclides are readily detectable by liquid scintillation counting, with the efficiency for²¹⁰Pb in the 60–70% range. The Cherenkov aqueous counting efficiency for²¹⁰Bi is ∼14–15%.     

Determination of 210Pb, 210Bi and 210Po in natural drinking water

A new method for the radioanalytical determination of the ²²²Rn progenies ²¹⁰Pb, ²¹⁰Bi and ²¹⁰Powill be presented, which has been improved for analyses of water samples fromdifferent regions in Austria. 1–2 liter samples were taken in polyethylenebottles prefilled with conc. HNO₃ to obtain 0.2M acidic solutions,thus avoiding adsorption effects. After adding 1.6 mg of inactive lead carrier,the water sample was evaporated to dryness, converted to the chloride formand dissolved in 1M HCl.     

An 227Ac-211Pb generator for test experiments of solution chemistry of element 114

A simple and effective method has been developed for the continuous production of the short-lived isotope Pb as a homolog of element 114 on the principle of a radionuclide generator. The method is based on the initial sorption of ²²⁷Ac or ²²³Ra on a small cation-exchange column, with subsequent “milking” of ²¹¹Pb (36.1 m) by a mixture of HCl/CH₃OH. The optimum conditions for the repeated separation of ²¹¹Pb from radionuclides strongly sorbed by the cation-exchanger (Ac, Th, Ra, Pu, TPE) have been determined. Possibilities of using the ²¹¹Pb generator for test experiments on the solution chemistry of element 114 have been shown. Advantages of aqueous alcohol HCl solutions for the isolation of ²¹¹Pb (element 114) are discussed. This revised version was published online in August 2006 with corrections to the Cover Date.     

Radiochemical separation of 82Sr and the preparation of a sterile 82Sr/82Rb generator column

Summary Ion-exchange chromatography using the chelating resins Purolite S950 and Chelex 100 was investigated for the radiochemical separation of ⁸²Sr from a RbCl target. 0.25M NH₄Cl solution was employed for the retention of Sr and elution of Rb, and 2M HCl for the elution of Sr. Although both resins showed very similar results, the conditions for adsorption of Sr were different. The ammonium chloride solution was directly used with Purolite S950 while it was necessary to adjust the pH between 9 and 10 with Chelex 100. Purolite S950 was, therefore, selected for routine production of ⁸²Sr. A procedure has been introduced for the preparation of a hydrous tin dioxide as supporting material for the ⁸²Sr/⁸²Rb generator column. All components of the generator column were made up of stainless steel. The column was 4 cm long, 9.5 mm O.D. and 7.1 mm I.D. Using isotonic saline (0.9% NaCl) for elution of ⁸²Rb, elution curves with different flow rates ranging from 5 to 20 ml/min were obtained. Maximum available ⁸²Rb was eluted in the first 20 ml. The column generator provided a sterile ⁸²Rb in isotonic saline. The breakthrough of ⁸²Sr over 4 weeks of elution using 7 liter of saline was on average 4.5 ^. 10^-5% (based on the first 20 ml eluate).     

Biodistribution of 212Pb conjugated trastuzumab in mice

The biodistribution in mice of ²¹²Pb-trastuzumab, a HER2 targeting immunoglobulin (monoclonal antibody), was investigated for its potential as a therapeutic agent with immunocytotoxic applications. ²¹²Pb-trastuzumab is an alpha-emitting radioimmunoconjugate that can deliver a short-range, high linear energy transfer (LET) radiation dose to targeted tissue. ²¹²Pb is an attractive isotope for medical applications because it is has a short half-life (10.64 h), and one of its decay products (²¹²Po) emits a very high LET alpha-particle (E = 8.78 MeV). Radiolabeled trastuzumab was found to be pure, functional, and intact by both ELISA and SDS-PAGE evaluation. The uptake and biodistribution of ²¹²Pb-trastuzumab was determined as a percentage of the injected dose by analysis of nine different organs obtained from serially sacrificed male nude mice bearing orthotopic tumors of PC-3MM2 human prostate carcinoma. High-resolution gamma spectrometry was used to determine the content of ²¹²Pb in each organ at several fixed times post intravenous injection. Although the PC-3MM2 cells express limited HER2 receptors, approximately 8 % of injected dose was observed in the tumor at 12 h post IV injection. Results of this biodistribution study support further investigation of radiolabeled ²¹²Pb-trastuzumab, radiobiological organ microdosimetry, and optimal dosing regimens for trastuzumab as a therapeutic agent.     

Ga2O for target, solvent extraction for radiochemical separation and SnO2for the preparation of a68Ge/68Ga generator

Summary The target for the production of⁶⁸Geconsists of a disc of gallium suboxide, Ga₂O, with a 19 mm diameter. The suboxide was primarily prepared by repeatedly mixing metallic Ga and Ga₂O₃at 700 °C. The target (2.4 g) was quite stable under a long-time irradiation with a 34 MeV proton beam at a current of ~80<span lang=EN-ZA style='font-size:12.0pt; font-family:Symbol;mso-bidi-font-family:Symbol;mso-ansi-language:EN-ZA'>mA. The dissolution of the target was performed using 12M sulphuric acid solution, assisted with the dropwise addition of 30% H₂O₂solution, and took less than 4 hours. A solvent extraction method, using a 9M H₂SO₄-0.3M HCl/CCl₄system, was employed for the radiochemical separation of⁶⁸Ge from Ga and Zn radionuclides, while 0.05M HCl was used for the back extraction of⁶⁸Ge from the organic phase. The⁶⁸Ge obtained in the dilute HCl was directly loaded onto a column containing either a hydrous tin dioxide or a crystalline tin dioxide, obtained by calcinations of the hydrous oxide at 450, 700, and 900 °C. The calcinated hydrous tin dioxide at 900 °C showed the highest crystallinity and highest⁶⁸Ga elution yield and was selected for use in the generator. The⁶⁸Ga elution from the column generator packed with 2 g of tin dioxide, using 3 ml of 1M HCl, and yielded an average of 65%. The breakthrough of⁶⁸Ge was 6.1^. 10^-4%.     

Improvement of quality in the evaluation of radium isotopes 224,226,228Ra in oil scale samples

Elevated concentrations of the radium isotopes ^224,226,228Ra exist in the scale and produced water in oil exploration. The activity concentration of ²²⁶Ra was calculated from 186.2 keV peak with no usual spectral interference of 185.7 from ²³⁵U. The activity concentration of ²²⁸Ra was calculated from its first daughter product ²²⁸Ac using the 911.2 keV gamma rays since it is a pure beta emitter. The activity concentration of ²²⁴Ra was calculated from ²¹²Pb using the 238.6 keV gamma-ray and the secular equilibrium equation with ²²⁸Ra. The IAEA 448 (oil contaminated field soil) reference material was used as a quality control for ^226,228Ra and but was unreliable for ²²⁴Ra using ²¹²Pb.

     

Comparative temporal behavior of radon- and thoron-progeny in surface air over the midwestern U.S.

Temporal variations in airborne²¹⁰Pb,²¹²Pb,²¹⁴Pb,²¹⁸Po, and²¹⁴Bi concentrations at Springfield, Missouri, USA, are compared with each other and with results reported from studies performed in other parts of the world. At Springfield diurnal concentration patterns of²¹⁰Pb are similar to those of²¹²Pb, but seasonal concentration patterns differ markedly. Additionally, abnormal disequilibrium conditions are sometimes found to exist in Springfield among²¹⁸Po,²¹⁴Pb, and²¹⁴Bi in which progeny/parent ratios are greater than 1. Findings similar to those presented here have been reported at some sites throughout the world, but different temporal patterns have been reported at others. Examination of concentration dependence on meteorological conditions at Springfield indicates that some of these differences are correlated with temperature and ground snow cover. Implications of these findings for use of thoron- and radon-progeny as atmospheric tracers are discussed.     

Separation of95Zr and95Nb from each other and from other fission products by adsorption and desorption on silica gel using hydrochloric acid solutions

The silica gel adsorption behaviour of zirconium, niobium, ruthenium and cerium in hydrochloric acid has been investigated by batch and column techniques. A satisfactory radiochemical separation of zirconium and niobium from each other and from other fission products has been achieved by a two column technique. The recommended procedure consists of sorption of all the nuclides on a primary silica gel column. Fifteen per cent of⁹⁵Nb, all of the zirconium and all of the other fission products are eluted first by washing with 5.5 M HCl. A second elution with concentrated hydrochloric acid then recovers the⁹⁵Nb (free from other products). The solution from the first elution after evaporation to 1 ml is then passed through another silica gel column and successively washed with 0.5M HCl, 5.5M HCl and concentrated HCl to obtain three fractions—other fission products—⁹⁵Zr free from other products—⁹⁵Nb free from other products, respectively.