Development of 166Ho-zoledronate as a bone marrow ablative agent

Abstract

In this study, production, quality control and biodistribution studies of 166 Hozoledronate have been presented as a possible bone marrow ablative agent. Ho-166 chloride was produced by thermal neutron irradiation of natural 165 Ho(NO 3) 3 samples. 166 Ho-zoledronate complex was prepared by adding the desired amount of zoledronate solution (0.2 mL, 150 mg/ml in 1 M NaOH) to appropriate amount of the 166 HoCl 3 solution. Radiochemical purity of the complex was monitored by instant thin layer chromatography (ITLC). Stability studies of the complex in the final preparation and in the presence of human serum were performed up to 48 h. The biodistribution of 166 Ho-zoledronate and 166 HoCl 3 in wild-type mice was checked up to 72 h. 166 Ho-zoledronate complex was prepared in high radiochemical purity (> 99%, ITLC) and specific activity of 4.4 GBq/mmol. The major accumulation of radiolabelled complex was observed in the bone tissue. These findings suggest 166 Ho-zoledronatehas can be a possible candidate for bone marrow ablation in patients with multiple myeloma.

High affinity zoledronate-based metal complex nanocrystals to potentially treat osteolytic metastases

“…[22][23][24][25] Several attempts have been made by employing ZOLE to design effective therapies against bone-related diseases, such as coordination complexes for drug delivery, 21,26,27 and radiopharmaceuticals as a bone pain therapy for oncological diseases. 15,[28][29][30] However, these approaches focused mainly on the labeling efficiency of ZOLE to beta emitters, adsorption to hydroxyapatite (HA), biodistribution, and cytotoxicity of the proposed systems through in vitro assays employing prostate, lung, and liver cancerous cells. 15,21,[26][27][28][29][30] Here, we propose to develop novel ZOLE-based coordination complex nanocrystals and assess their potential to treat specifically breast-cancer-induced OM.…”

“…15,[28][29][30] However, these approaches focused mainly on the labeling efficiency of ZOLE to beta emitters, adsorption to hydroxyapatite (HA), biodistribution, and cytotoxicity of the proposed systems through in vitro assays employing prostate, lung, and liver cancerous cells. 15,21,[26][27][28][29][30] Here, we propose to develop novel ZOLE-based coordination complex nanocrystals and assess their potential to treat specifically breast-cancer-induced OM.…”