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.

• Authors: S J Oh, K S Won, D H Moon, J H Cheon, H-J Ha, J M Jeong, H K Lee
• Journal: Nuclear medicine communications (Nucl Med Commun) Vol. 23 Issue 1 Pg. 75-81 (Jan 2002) ISSN: 0143-3636 [Print] England
• PMID: 11748441 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Indicators and Reagents
• Ligands
• Organometallic Compounds
• Radioisotopes
• Radiopharmaceuticals
• Reducing Agents
• rhenium ethylenediamine-N,N,N',N'-tetrakis(methylene phosphonic acid)

Topics

• Animals
• Bone Neoplasms (physiopathology, secondary)
• Hydrogen-Ion Concentration
• Indicators and Reagents
• Isotope Labeling (methods)
• Ligands
• Male
• Organometallic Compounds (chemical synthesis, pharmacokinetics, therapeutic use)
• Pain, Intractable (drug therapy, etiology)
• Radioisotopes (pharmacokinetics, therapeutic use)
• Radiopharmaceuticals (chemical synthesis, pharmacokinetics, therapeutic use)
• Rats
• Rats, Wistar
• Reducing Agents
• Tissue Distribution