Production, quality control, and determination of human absorbed dose of no carrier added 177 Lu-risedronate for bone pain palliation therapy

Abstract

In this study, the radiocomplexation of risedronic acid, a potent bisphosphonate with a no carrier added (NCA) ¹⁷⁷ Lu, was investigated and followed by quality control studies, biodistribution evaluation, and dosimetry study for human based on biodistribution data in Wistar rats. The moderate energy β^- emitter, ¹⁷⁷ Lu (T_½ = 6.7 days, E_βmax = 497 keV), has been considered as a potential agent for development of bone-seeking radiopharmaceuticals. Because the specific activity of the radiolabeled carrier molecules should be high, the NCA radionuclides have an effective role in nuclear medicine. Many researchers illustrated an NCA ¹⁷⁷ Lu production; among these separation techniques, extraction chromatography has been considered more capable than other methods. The NCA ¹⁷⁷ Lu was produced with specific activity of 48 Ci/mg and radionuclidic purity of 99.99% by the irradiation of enriched ¹⁷⁶ Yb target in thermal neutron flux of 4 × 10¹³ n·cm^-2 ·s^-1 for 14 days. The NCA ¹⁷⁷ Lu was mixed to a desired amount of sodium risedronate (15 mg/mL, 200 μL) and incubated with stirring at 95°C for 30 minutes. The radiochemical purity of ¹⁷⁷ Lu-risedronate was determined by radio thin-layer chromatography, and high radiochemical purities (>97%) were obtained under optimized reaction conditions. The complex was injected to Wistar rats, and complex biodistribution was performed 4 hours to 7 days postinjections showing high bone uptake (9.8% ± 0.24% ID/g at 48 hours postinjection). Also, modeling the radiation dose delivery by RADAR software for the absorbed dose evaluation of each human organ showed a major accumulation of the radiocomplex in bone tissue.

Keywords: 177Lu; RADAR software; extraction chromatography; no carrier added.