Separation and purification of no-carrier-added arsenic from bulk amounts of germanium for use in radiopharmaceutical labelling

Abstract

72 As, 74 As, 77 As / Radioactive arsenic / Germanium target / Radiochemical separation / Labelled antibodies Summary. Radioarsenic labelled radiopharmaceuticals could add special features to molecular imaging with positron emission tomography (PET). For example the long physical half-lives of 72 As (T 1/2 = 26 h) and 74 As (T 1/2 = 17.8 d) in conjunction with their high positron branching rates of 88% and 29%, respectively, allow the investigation of slow physiological or metabolical processes, like the enrichment and biodistribution of monoclonal antibodies in tumour tissue or the characterization of stem cell trafficking. A method for separation and purification of no-carrier-added (nca) arsenic from irradiated metallic germanium targets based on distillation and anion exchange is developed. It finally converts the arsenic into an * As(III) synthon in PBS buffer and pH 7 suitable for labelling of proteins via As−S bond formations. The method delivers radioarsenic in high purity with separation factors of 10 6 from germanium and an overall yield from target to labelling synthon of > 40%. In a proof-ofprinciple experiment, the monoclonal antibody Bevacizumab, directed against the human VEGF receptor, was labelled with a radiochemical yield > 90% within 1 h at room temperature with nca 72/74/77 As.

High Yield Production and Radiochemical Isolation of Isotopically Pure Arsenic-72 and Novel Radioarsenic Labeling Strategies for the Development of Theranostic Radiopharmaceuticals

“…The reduction and SPE procedures detailed in this manuscript were adapted from Jahn et al 19 and Jennewein et al, 13 respectively. The result is significantly more automatable and resulted in less radiation worker dose exposure compared with the liquid-phase solvent extraction procedure adapted from Jahn et al 19 and Shehata et al 14 The conditions utilized in this work resulted in reasonable yields of 72 As in a small volume of buffered eluant, with (57 ± 5)% yield in the first 300 μ L of 1 M HEPES.…”

Chromatographic separation of germanium and arsenic for the production of high purity 77As

“…Many methods to isolate As from Ge have been reported including solvent extraction [5, 6], distillation [7, 8], ion exchange [8-10], solid phase extraction [11-13], and thin layer chromatography [14]. The solvent extraction methods reported often involve several labor intensive steps, including back extractions, and are not readily adapted for high activity separations requiring remote handling.…”

“…The solvent extraction methods reported often involve several labor intensive steps, including back extractions, and are not readily adapted for high activity separations requiring remote handling. Distillation methods require heating, some to high temperature (1105 °C [7]), which increases sample processing time and may require further radioarsenic purification [8]. Chromatographic methods involving ion exchange or solid phase adsorption provide an efficient, robust purification method more readily adapted to automated, remote handling required with high levels of radioactivity.…”

“…Chromatographic methods involving ion exchange or solid phase adsorption provide an efficient, robust purification method more readily adapted to automated, remote handling required with high levels of radioactivity. Many of the current literature methods involve the use of strong acids (e.g., >8 M HNO 3 , HF, HCl) in the separation process, which are undesirable for radionuclides that will be used for synthesizing radiopharmaceuticals [8-12]. Chakravarty [13] reported a two-column separation for high purity radioarsenic from a GeO 2 target using nanocrystalline titania.…”

Polymer Embedded Nanocrystalline Titania: A New Generation Sorbent for the Separation of 77As from Ge for Biomedical Applications

“…This requires efficient radiochemical separation of 77 As from large amounts of Ge target material. In the past few years, there have been considerable efforts towards development of effective separation techniques involving distillation, co-precipitation, solvent extraction, thin layer chromatography, etc., for the isolation of 77 As from cyclotron or reactor irradiated germanium or germanium oxide targets [13][14][15][16][17][18][19][20][21][22][23].…”