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The article presents a novel gas-chemical approach for 225Ac/213Bi generators, which provides effective separation of 213Bi from parent 225Ac. The main problem with the generators of high activity is the radiation stability of sorbents, which is not substantial in this gas-chemical method of separation, where only radiationally stable inorganic materials are used. The approach includes heating at high temperature (about 900–1000 °C) 225Ac sample deposited on a backing material (Nb, quartz glass, stainless steel) in hydrogen-containing inert gas flow. Actinium is non-volatile in these conditions, while Bi sublimes and is deposited on a catcher-foil along a temperature gradient. Niobium was found to be the best of the used material for both the starting backing and catcher-foil. The effective activation energy of carrier-free amount of Bi-sublimation from Nb-backing as 102 ± 9 kJ/mol has been calculated, and standard enthalpy of desorption of Bi on Nb from thermochromatographic data has been evaluated as 269 ± 13 kJ/mol 213Bi may be recovered for the consequent preparation of radiopharmaceuticals by washing from the catcher-foil surface. The gas-chemical method has been demonstrated to be a promising approach for 225Ac/213Bi generators for its application in targeted alpha therapy. • A new approach for an 225Ac/213Bi generator tackles the challenge of radiation stability of materials in existing generators. • The difference in actinium and bismuth volatilities in a reducing atmosphere allows for effective separation of 213Bi. • The effective activation energy of NCA Bi sublimation from Nb-backing and its adsorption enthalpy on Nb have been measured. [ABSTRACT FROM AUTHOR]

The radiation resistance of sorbents AG 50 W-X8, Ac resin, and UTEVA resin in contact with hydrochloric solutions under irradiation with 10 MeV electrons in a wide absorbed-dose range up to 2 MGy was studied. Mass distribution ratios and total sorption capacity were used as quantitative measures to determine the changes in ion exchange or extractive abilities of the resins. Based on the data obtained and on a review of the performance of the 225Ac/213Bi generators reported in the literature, the applicability of investigated resins for high activity loaded onto different generator systems was concluded. [ABSTRACT FROM AUTHOR]

Scheme of a two-column 225Ac/213Bi generator using inorganic sorbents based on hydrated titanium oxide (JSC "Termoxid") and hydrated zirconium oxide modified with nickel-potassium ferrocyanide (Termoxid, T-35) is suggested. 213Bi is obtained via a prolonged washing-out of 221Fr from the first column with T-5 sorbent containing 225Ac and its retention in the second column with T-35 for the decay and accumulation of 213Bi, which is extracted afterwards with a 1 M HCl solution. The direct-flow and circulatory schemes were tested, and the properties of the generator toward radionuclides of the 225Ac subfamily were determined in a wide range of flow rates and eluent volumes. It is assumed that the sorbents of the T-5 and T-35 brands are suitable for creating a 225Ac/213Bi generator with activity of hundreds of 225Ac mCi. [ABSTRACT FROM AUTHOR]

A new two-column 225Ac/213Bi generator was developed specifically for using 225Ac containing an impurity of long lived 227Ac. The parent 225Ac was retained on the first Actinide Resin column, while 213Bi was accumulated on the second column filled with AG MP-50 resin via continuous elution and decay of intermediate 221Fr. The 213Bi accumulation was realized in circulation mode which allowed a compact generator design. It was demonstrated that 213Bi could be quickly and effectively extracted from AG MP-50 in form of complexes with various chelating agents including DTPA and DOTA. The performance of the generator presented and a conventional single-column generator on the base of AG MP-50 was tested and both generators were loaded with 225Ac containing 227Ac impurity. The 213Bi generation efficiencies were comparable and greater than 70%, whereas the developed generator provided a deeper degree of purification of 213Bi from Ac isotopes and decay products of 227Ac.

A scheme of an "inverse" generator based on an inorganic sorbent (annealed zirconium and yttrium mixture oxides) has been proposed and tested. The generator demonstrated high yield of the 213Bi product (up to 97 % in 0.5 mL of eluate), high degree of purification from the actinium isotopes (up to 10−2 % of initial 225Ac in 3 M NaNO3 solution), as well as the products of 227Ac decay, and low radiation impact on the sorbent. Application of circulating approach to the sorption of 213Bi provides decreasing processing time to 5 min at higher yield of the product. [ABSTRACT FROM AUTHOR]

Binding of bismuth cation with two newly synthesized picolinate containing acyclic (L1) and macrocyclic (L2) ligands was studied. Both ligands demonstrate complex formation with Bi3+ under ambient conditions with high complexation constants. Serum stability of the complexes was investigated in serum protein excess of 10- and 100-times. Experiments with no-carrier-added radiobismuth (207Bi and 213Bi) were performed. A one-column 225Ac/213Bi generator system, based on Ac resin (Triskem Inc.), was tested. The overall yield of 213Bi was exceeding 85% with 225Ac breakthrough below 10−4%. [ABSTRACT FROM AUTHOR]

The ability of inorganic hydroxide sorbents Termoxid-5 (T-5) and Termoxid-39 (T-39) heat-treated at temperatures from 100 to 950°C to take up radionuclides of the 225Ac subfamily was examined in a wide range of solution acidities and salt compositions. T-5 and T-39 are principally suitable for the development of both direct and inverse 225Ac/213Bi generators with the activity of hundreds of millicuries of 225Ac. [ABSTRACT FROM AUTHOR]

Purpose: Patients with carcinoma in situ (CIS) of the bladder refractory to bacillus Calmette-Guérin (BCG) treatment are usually treated with cystectomy. Therefore, new treatment options with preservation of the urinary bladder are needed. The objective of the study was to investigate the feasibility, safety and efficacy of a novel targeted alpha-emitter immunotherapy for CIS after BCG treatment failure.Methods: A pilot study was conducted in 12 patients (age range 64-86 years, ten men, two women) with biopsy-proven CIS of the bladder refractory to BCG treatment. The patients were treated intravesically with a single instillation (one patient was treated twice) of the alpha-emitter 213Bi coupled to an anti-EGFR antibody (366-821 MBq). The primary aims of the study were to determine the feasibility of treatment with the 213Bi-immunoconjugate and evaluation of adverse effects. Therapeutic efficacy was monitored by histological mapping of the urinary bladder 8 weeks after treatment and at different time points thereafter.Results: The study proved that intravesical instillation of the 213Bi-immunoconjugate targeting EGFR is feasible. No adverse effects were observed and all blood and urine parameters determined remained in their normal ranges. Therapeutic efficacy was considered satisfactory, in that three of the 12 patients showed no signs of CIS 44, 30 and 3 months after treatment.Conclusion: Intravesical instillation of 213Bi-anti-EGFR monoclonal antibody was well tolerated and showed therapeutic efficacy. Repeated instillation and/or instillation of higher activities of the 213Bi-immunoconjugate might lead to better therapeutic outcomes. A phase I clinical trial is planned. [ABSTRACT FROM AUTHOR]

A new two-column 225Ac/213Bi generator was developed specifically for using 225Ac containing an impurity of long lived 227Ac. The parent 225Ac was retained on the first Actinide Resin column, while 213Bi was accumulated on the second column filled with AG MP-50 resin via continuous elution and decay of intermediate 221Fr. The 213Bi accumulation was realized in circulation mode which allowed a compact generator design. It was demonstrated that 213Bi could be quickly and effectively extracted from AG MP-50 in form of complexes with various chelating agents including DTPA and DOTA. The performance of the generator presented and a conventional single-column generator on the base of AG MP-50 was tested and both generators were loaded with 225Ac containing 227Ac impurity. The 213Bi generation efficiencies were comparable and greater than 70%, whereas the developed generator provided a deeper degree of purification of 213Bi from Ac isotopes and decay products of 227Ac. [ABSTRACT FROM AUTHOR]