Production, Quality Control and Pharmacokinetic Studies of 166Ho-EDTMP for Therapeutic Applications

Abstract

166Ho-EDTMP is a major therapeutic agent which is widely used in bone palliation therapy. In this study, a 166Ho-EDTMP complex was prepared successfully using an in-house synthesized EDTMP ligand and 166HoCl3. Ho-166 chloride was obtained by thermal neutron irradiation (1 × 1013 ncm−2s−1) of natural Ho(NO3)3 samples (specific activity = 3–5 GBq/mg), dissolved in acidic media. The radiochemical purity of 166Ho-EDTMP was checked by ITLC (>99%) and stability studies in presence of human serum and final preparation were performed. The biodistribution of 166Ho-EDTMP and 166HoCl3 in wild-type rats was checked by scarification. SPECT imaging of 166Ho-EDTMP was also performed in wild-type rats. A comparative accumulation study for 166Ho-EDTMP and 166HoCl3 was performed for vital organs up to 48h. Significant bone accumulation (>70%) of the tracer in 48h was observed.

Development of 166Ho-pamidronate for bone pain palliation therapy

“…As a comparable 166 Ho bone pain palliation agent, 166 Ho-EDTMP has been proposed as a potential clinically used radiopharmaceutical by different groups [7,10]. A low liver uptake has been reported for 166 Ho-EDTMP which is considered a disadvantage as a bone pain palliative agent leading to less unwanted liver dose in patients (Fig.…”

“…The use of bisphosphonates has made a significant change in the therapeutic approach to management of bone metastasis and pain prevention in breast cancer and multiple myeloma [4]. Various therapeutic 166 Ho bone-seeking agents have been reported such as 166 Ho-DOTMP [5,6], 166 Ho-EDTMP [7,8], 166 Ho-AP-DDMP [9], as well as 166 Dy/ 166 Ho-EDTMP demonstrating adequate properties as a stable in vivo generator system for bone marrow ablation [10].…”

Production and Clinical Applications of Radiopharmaceuticals and Medical Radioisotopes in Iran

“…Total synthesis and production of 177 Lu-EDTMP were performed in the country and preclinical studies were reported in 2012. 61…”

Palliative treatment of metastatic bone pain with radiopharmaceuticals: A perspective beyond Strontium-89 and Samarium-153

“…Pre-clinical trials in dogs showed that 177 Lu-EDTMP is taken up almost exclusively by the skeletal system (>70%), with minimal activity accumulation in other organs (Bahrami-samani et al, 2012;Máthé et al, 2010;Saeed et al, 2012). Clinical trials with 177 Lu-EDTMP showed an obvious reduction in the pain scores at 2 to 6 weeks after the radiopharmaceutical administration.…”