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

Abstract

In this study, the radiocomplexation of risedronic acid, a potent bisphosphonate with a no carrier added (NCA) 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, Lu (T = 6.7 days, E = 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 Lu production; among these separation techniques, extraction chromatography has been considered more capable than other methods. The NCA Lu was produced with specific activity of 48 Ci/mg and radionuclidic purity of 99.99% by the irradiation of enriched Yb target in thermal neutron flux of 4 × 10 n·cm ·s for 14 days. The NCA 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 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.

Human Absorbed Dose Evaluation of [177Lu]Lu-IBA as a Bone Palliative Candidate

“…These properties makes it an appropriate choice to produce different radiopharmaceuticals based on uses. There are many new scientific works on radiolabeled bone seeking ligands like [ 177 Lu]Lu-DOTA-ZOL, [ 177 Lu]Lu-Residronate that dosimetric assessments have also been done in some of them [9,10].…”

Preparation and Evaluation of 177Lu-TDTMP: A Potential Theranostic Agent for Bone Metastases

“…Metastatic bone lesion (MBL) is a major clinical concern associated with an obvious mortality and morbidity [1]. MBL is commonly observed in advanced state of many cancers especially breast, lung, prostate and bladder carcinoma [2,3]. Its incidence is increasing and can reach 95% depending on the primary cancer type [4].…”