title: Production, quality control, and determination of human absorbed dose of no carrier added177Lu-risedronate for bone pain palliation therapy.
abstract: In this study, the radiocomplexation of risedronic acid, a potent bisphosphonate with a no carrier added (NCA)177Lu, 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,177Lu (T½= 6.7 days, Eβmax= 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 NCA177Lu production; among these separation techniques, extraction chromatography has been considered more capable than other methods. The NCA177Lu was produced with specific activity of 48 Ci/mg and radionuclidic purity of 99.99% by the irradiation of enriched176Yb target in thermal neutron flux of 4 × 1013n·cm-2·s-1for 14 days. The NCA177Lu 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 of177Lu-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.
authors.affiliation: Nuclear Fuel Cycle Research School, Nuclear Science and Technology Research Institute, Tehran, Iran.|Faculty of Energy Engineering and Physics, Amirkabir University of Technology, Tehran, Iran.
authors.forename: Nafise
authors.initials: N
authors.lastname: Salek
authors.affiliation: Faculty of Energy Engineering and Physics, Amirkabir University of Technology, Tehran, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Mehrabi
authors.affiliation: Nuclear Fuel Cycle Research School, Nuclear Science and Technology Research Institute, Tehran, Iran.
authors.forename: Simindokht
authors.initials: S
authors.lastname: Shirvani Arani
authors.affiliation: Nuclear Fuel Cycle Research School, Nuclear Science and Technology Research Institute, Tehran, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Bahrami Samani
authors.affiliation: Nuclear Fuel Cycle Research School, Nuclear Science and Technology Research Institute, Tehran, Iran.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Erfani
authors.affiliation: Nuclear Fuel Cycle Research School, Nuclear Science and Technology Research Institute, Tehran, Iran.
authors.forename: Sara
authors.initials: S
authors.lastname: Vosoghi
authors.affiliation: Nuclear Fuel Cycle Research School, Nuclear Science and Technology Research Institute, Tehran, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ghannadi Maragheh
authors.affiliation: Faculty of Energy Engineering and Physics, Amirkabir University of Technology, Tehran, Iran.
authors.forename: Mojtaba
authors.initials: M
authors.lastname: Shamsaei
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000378:metabolism / Q000528:radiation effects; D000072716:Cancer Pain / Q000188:drug therapy*; D002478:Cells, Cultured; D006801:Humans; D008187:Lutetium / Q000737:chemistry*; D011829:Radiation Dosage; D011868:Radioisotopes / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics / Q000592:standards; D051381:Rats; D017208:Rats, Wistar; D000068296:Risedronic Acid / Q000737:chemistry*; D014018:Tissue Distribution
chemical_list: D011868:Radioisotopes; D019275:Radiopharmaceuticals; D008187:Lutetium; D000068296:Risedronic Acid
keywords: 177Lu; RADAR software; extraction chromatography; no carrier added