Production, quality control and pharmacokinetic studies of [sup.177]Lu-zoledronate for bone pain palliation therapy

• Published in: Journal of radioanalytical and nuclear chemistry 2013-11, Vol.298 (2), p.1273
• Main Authors: Nikzad, Mirsaeed, Jalilian, Amir R, Shirvani-Arani, Simindokht, Bahrami-Samani, Ali, Golchoubian, Hamid
• Format: Article
• Language: English
• Subjects: Quality control
• ISSN: 0236-5731
• DOI: 10.1007/s10967-013-2490-2

Developing new bone pain palliation agents are a mandate in handling end-stage cancer patient's around the world. [sup.177]Lu (1-hydroxy-2-imidazol-1-yl-phosphonoethyl)-phosphonic acid ([.sup.177]Lu-ZLD) is a possible therapeutic agent which can be used in bone palliation therapy. In this study, [sup.177]Lu-ZLD complex was prepared successfully using commercial ZLD ligand and [sup.177]Lu[Cl.sub.3] at 25 and 60°C at various ligand:metal ratios for 60-360 min. [sup.177]Lu chloride was obtained by thermal neutron irradiation (4 x [10.sup.13] n [cm.sup.-2][s.sup.-1]) of natural [Lu.sub.2][O.sub.3] samples. Radiochemical purity of [sup.177]Lu-ZLD was checked by ITLC and HPLC. Stability studies of final preparation in the presence of human serum were performed as well as protein binding studies and hydroxyapatite (HA) binding test. The biodistribution of [sup.177]Lu-ZLD and [sup.177]Lu[Cl.sub.3] in mice were determined for 7 days. A comparative accumulation study for [sup.177]Lu-ZLD and [sup.177]Lu-EDTMP was performed for vital organs up to 7 days. The complex was obtained in high radiochemical purity ITLC (> 97%) and HPLC (> 99.9%) and satisfactory stability in presence of human serum and final formulations were obtained ([approximately equal to] 90% in 48 h). HA binding assay demonstrated > 95% binding from 5 to 20 mg of HA in 24 h at room temperature. The complex protein binding was about 55-58%. The high bone uptake ratios at all time intervals was obtained (> 9% at day 7), bone: kidney and bone: liver uptake ratios were significantly high for ZLD at 7 day post injection but not superior to [sup.177]Lu-EDTMP. Due to longer physical half life of [sup.177]Lu compared to [sup.153]Sm and comparable ratios for [sup.177]Lu-ZLD compared to [sup.177]Lu-EDTMP, [sup.177]Lu-ZLD can be an interesting new candidate for clinical trials for bone pain palliation therapy. Keywords [sup.177]Lu Zoledronic acid * Bone pain palliation therapy * Biodistribution* Pharmacokinetics