Sustainable production of radionuclidically pure antimony-119

Abstract

Background

Radiopharmaceutical therapy (RPT) uses radionuclides that decay via one of three therapeutically relevant decay modes (alpha, beta, and internal conversion (IC) / Auger electron (AE) emission) to deliver short range, highly damaging radiation inside of diseased cells, maintaining localized dose distribution and sparing healthy cells. Antimony-119 (¹¹⁹Sb, t_1/2 = 38.19 h, EC = 100%) is one such IC/AE emitting radionuclide, previously limited to in silico computational investigation due to barriers in production, chemical separation, and chelation. A theranostic (therapeutic/diagnostic) pair can be formed with ¹¹⁹Sb’s radioisotopic imaging analogue ¹¹⁷Sb (t_1/2 = 2.80 h, E_γ = 158.6 keV, I_γ = 85.9%, β⁺ = 262.4 keV, I_β+ = 1.81%).

Results

Within, we report techniques for sustainable and cost-effective production of pre-clinical quality and quantity, radionuclidically pure ¹¹⁹Sb and ¹¹⁷Sb, novel low energy photon measurement techniques for ¹¹⁹Sb activity determination, and physical yields for various tin target isotopic enrichments and thicknesses using (p, n) and (d, n) nuclear reactions. Additionally, we present a two-column separation providing a radioantimony yield of 73.1% ± 6.9% (N = 3) and tin separation factor of (6.8 ± 5.5) x 10⁵ (N = 3). Apparent molar activity measurements for deuteron produced ¹¹⁷Sb using the chelator TREN-CAM were measured at 42.4 ± 25 MBq ¹¹⁷Sb/µmol (1.14 ± 0.68 mCi/µmol), and we recovered enriched ¹¹⁹Sn target material at a recycling efficiency of 80.2% ± 5.5% (N = 6) with losses of 11.6 mg ± 0.8 mg (N = 6) per production.

Conclusion

We report significant steps in overcoming barriers in ¹¹⁹Sb production, chemical isolation and purification, enriched target material recycling, and chelation, helping promote accessibility and application of this promising therapeutic radionuclide. We describe a method for ¹¹⁹Sb activity measurement using its low energy gamma (23.87 keV), negating the need for attenuation correction. Finally, we report the largest yet-measured ¹¹⁹Sb production yields using proton and deuteron irradiation of natural and enriched targets and radioisotopic purity > 99.8% at end of purification.