Preparation and biological evaluation of 188Re-ethylenediamine-N,N,N',N'-tetrakis(methylene phosphonic acid) as a potential agent for bone pain palliation.
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.
Oh
S J
SJ
Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea. sjoh@www.amc.seoul.kr
Won
K S
KS
Moon
D H
DH
Cheon
J H
JH
Ha
H-J
HJ
Jeong
J M
JM
Lee
H K
HK
D000818:Animals; D001859:Bone Neoplasms / Q000503:physiopathology / Q000556:secondary*; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D007553:Isotope Labeling / Q000379:methods; D008024:Ligands; D008297:Male; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010148:Intractable Pain / Q000188:drug therapy* / Q000209:etiology; D011868:Radioisotopes / Q000493:pharmacokinetics / Q000627:therapeutic use; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D019163:Reducing Agents; D014018:Tissue Distribution
D007202:Indicators and Reagents; D008024:Ligands; D009942:Organometallic Compounds; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D019163:Reducing Agents; C449682:rhenium ethylenediamine-N,N,N',N'-tetrakis(methylene phosphonic acid)