Recovery of high specific activity molybdenum-99 from accelerator-induced fission on low-enriched uranium for technetium-99m generators

A new process was developed to recover high specific activity (no carrier added) 99Mo from electron-accelerator irradiated U3O8 or uranyl sulfate targets. The process leverages a novel solvent extraction scheme to recover Mo using di(2-ethylhexyl) phosphoric acid following uranium and transuranics removal with tri-n-butyl phosphate. An anion-exchange concentration column step provides a final purification, generating pure 99Mo intended for making 99Mo/99mTc generators. The process was demonstrated with irradiated uranium targets resulting in more than 95% 99Mo recovery and without presence of fission products or actinides in the product.

In Vitro Evaluation of No-Carrier-Added Radiolabeled Cisplatin ([189, 191Pt]cisplatin) Emitting Auger Electrons

Due to their short-range (2–500 nm), Auger electrons (Auger e−) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Auger e−, it remains challenging to maximize the interaction between Auger e− and DNA. To assess the DNA-damaging effect of Auger e− released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [189, 191Pt]cisplatin and evaluated both its in vitro properties and DNA-damaging effect. Cellular uptake, intracellular distribution, and DNA binding were investigated, and DNA double-strand breaks (DSBs) were evaluated by immunofluorescence staining of γH2AX and gel electrophoresis of plasmid DNA. Approximately 20% of intracellular radio-Pt was in a nucleus, and about 2% of intra-nucleus radio-Pt bound to DNA, although uptake of n.c.a. radio-cisplatin was low (0.6% incubated dose after 25-h incubation), resulting in the frequency of cells with γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by the release of Auger e− very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger e−.

Synthesis of no-carrier-added [188, 189, 191Pt]cisplatin from a cyclotron produced 188, 189, 191PtCl42− complex

We developed a novel method for production of no-carrier-added (n.c.a.) [188, 189, 191Pt]PtIICl42− from an Ir target material, and then synthesized n.c.a. [*Pt]cis-[PtIICl2(NH3)2] ([*Pt]cisplatin) from [*Pt]PtIICl42−. [*Pt]PtIICl42− was prepared as a synthetic precursor of n.c.a. *Pt complex by a combination of resin extraction and anion-exchange chromatography after the selective reduction of IrIVCl62− with ascorbic acid. The ligand-substitution reaction of Cl with NH3 was promoted by treating n.c.a. [*Pt]PtIICl42− with excess NH3 and heating the reaction mixture, and n.c.a. [*Pt]cisplatin was successfully produced without employing precipitation routes. After this treatment, [*Pt]cisplatin was isolated through preparative HPLC with a radiochemical purity of 99 + % at the end of synthesis (EOS).

In Vitro Evaluation of No-carrier-added Radiolabeled Cisplatin ([189, 191Pt]cisplatin) Emitting Auger Electrons

Due to their short range (2–500 nm), Auger electrons (Auger e-) have the potential to induce nano-scale physiochemical damage to biomolecules. Although DNA is the primary target of Au-ger e-, it remains challenging to maximize the interaction between Auger e- and DNA. To assess the DNA-damaging effect of Auger e- released as close as possible to DNA without chemical damage, we radio-synthesized no-carrier-added (n.c.a.) [189, 191Pt]cisplatin and evaluated both its in vitro properties and DNA-damaging effect. Cellular uptake, intracellular distribution, and DNA binding were investigated, and DNA double-strand breaks (DSBs) were evaluated by im-munofluorescence staining of γH2AX and gel electrophoresis of plasmid DNA. Approximately 20% of intracellular radio-Pt was in a nucleus, and about 2% of intra-nucleus radio-Pt bound to DNA, although uptake of n.c.a. radio-cisplatin was low (0.6% incubated dose after 25-h incuba-tion), resulting in the frequency of cells with γH2AX foci was low (1%). Nevertheless, some cells treated with radio-cisplatin had γH2AX aggregates unlike non-radioactive cisplatin. These findings suggest n.c.a. radio-cisplatin binding to DNA causes severe DSBs by release of Auger e- very close to DNA without chemical damage by carriers. Efficient radio-drug delivery to DNA is necessary for successful clinical application of Auger e-.

Production of no-carrier-added 89Zr at an 18 MeV cyclotron, its purification and use in investigations in solvent extraction

The chemical separation of zirconium from lanthanides by liquid–liquid extraction is challenging but critical for medical and technological applications. Using the example of 89Zr, we optimize the liquid–liquid-extraction process by means of the radiotracer technique. We produced 89Zr by proton irradiation of a metallic yttrium target at a cyclotron. The purification of the radionuclide was performed by a UTEVA resin. 89Zr was separated in no-carrier-added form in a sulfuric acid solution. 89Zr was successfully used in solvent extraction tests with calixarenes for the separation of zirconium from lanthanides. This reaction is suitable for the efficient extraction and purification of lanthanides.

Separation of no-carrier-added 71,72As from 46 MeV alpha particle irradiated gallium oxide target

No-carrier-added (NCA) 71,72As radionuclides were produced by irradiating gallium oxide target by 46 MeV α-particles. NCA 71,72As was separated from the target matrix by liquid-liquid extraction (LLX) using trioctyl amine (TOA) and tricaprylmethylammonium chloride (aliquat-336) diluted in cyclohexane. The bulk gallium was quantitatively extracted into the organic phase leaving 71,72As in the aqueous phase. Complete separation was observed at 3 M HCl + 0.1 M TOA and 2 M HCl + 0.01 M aliquat-336.