The synthesis, radiolabeling and first biological evaluation of a new 166Ho-complex for radiotherapy of bone metastases

Abstract

Abstract In this study, the 166Ho-triethylene tetramine hexa (methylene phosphonic acid) (166Ho-TTHMP) complex was prepared as a bone palliation agent. The complex was successfully prepared using an in-house synthesized TTHMP ligand and [166Ho]HoCl3. Ho-166 chloride was obtained by thermal neutron irradiation (1×1013 n cm−2 s−1) of natural Ho(NO3)3 samples, followed by radiolabeling and stability studies. Biodistribution studies were also performed in wild type rats. The complex was prepared with the specific activity of 3–5 GBq/mg and a high radiochemical purity > 99%, (checked by ITLC). The 166Ho-TTHMP complex was stable in the final preparation and in the presence of human serum (> 90%) up to 72 h. The biodistribution of 166Ho-TTHMP in wild-type rats demonstrated significant bone uptake compared to 166HoCl3 up to 48 h. SPECT imaging of the radiolabeled compound was demonstrated to be in complete accordance with the biodistribution data. The major uptake was observed for long bones including thigh bones as well as skull and also knee and vertebrae. Primary properties of 166Ho-TTHMP demonstrate that this new therapeutic agent can be a good choice for metastatic bone pains.