Preparation and biological evaluation of 188Re-ethylenediamine-N,N,N',N'-tetrakis(methylene phosphonic acid) as a potential agent for bone pain palliation.

Abstract

This study was undertaken in order to prepare 188Re labelled ethylenediamine-N,N,N',N'-tetrakis(methylene phosphonic acid) (EDTMP), and to determine its potential as a therapeutic radiopharmaceutical for the palliation of metastatic bone pain. The effects of pH, incubation methods, and concentrations of stannous chloride, EDTMP, and ammonium perrhenate as a carrier on radiochemical yield and stability were evaluated. Biodistribution studies were performed in male Wistar rats after intravenous injection of 188Re-EDTMP and compared with those of hydroxyethylidene diphosphonate (HEDP). Greater than 95% radiochemical yield of 188Re-EDTMP was obtained under the optimal conditions (0.1 mmol x ml(-1) of EDTMP, 0.5 mg x ml(-1) of stannous chloride, and pH 1.0). Heating the reaction mixture (boiling water for 15 min, and microwave heating for 15 s) and the addition of ammonium perrhenate increased the radiochemical stability (>90% at 3 h, and >80% at 48 h). The biodistribution of 188Re-EDTMP showed high bony uptake and rapid clearance from other organs, and high bone-to-soft tissue ratios, which are similar to 188Re-HEDP. In conclusion, 188Re-EDTMP was prepared with high radiochemical yield and stability, and showed favourable biological characteristics. Microwave heating was a convenient and rapid method for the preparation of 188Re-EDTMP. It is considered that 188Re-EDTMP is a potential therapeutic agent for bone metastasis.