title: Thorium and actinium polyphosphonate compounds as bone-seeking alpha particle-emitting agents.
abstract: The present study explores the use of alpha-particle-emitting, bone-seeking agents as candidates for targeted radiotherapy. Actinium and thorium 1,4,7,10 tetraazacyclododecane N,N',N'',N''' 1,4,7,10-tetra(methylene) phosphonic acid (DOTMP) and thorium-diethylene triamine N,N',N'' penta(methylene) phosphonic acid (DTMP) were prepared and their biodistribution evaluated in conventional Balb/C mice at four hours after injection. All three bone-seeking agents showed a high uptake in bone and a low uptake in soft tissues. Among the soft tissue organs, only kidney had a relatively high uptake. The femur/kidney ratios for 227Th-DTMP, 228-Ac-DOTMP and 227Th-DOTMP were 14.2, 7.6 and 6.0, respectively. A higher liver uptake of 228Ac-DOTMP was seen than for 227Th-DTMP and 227Th-DOTMP. This suggests that some demetallation of the 228Ac-DOTMP complex had occurred. The results indicate that 225Ac-DOTMP, 227Th-DOTMP and 227Th-DTMP have promising properties as potential therapeutic bone-seeking agents.
authors.affiliation: Department of Chemistry, University of Oslo, P.O. Box 1033, Blindern, N-0315 Oslo, Norway.
authors.forename: Gjermund
authors.initials: G
authors.lastname: Henriksen
authors.forename: Oyvind S
authors.initials: OS
authors.lastname: Bruland
authors.forename: Roy H
authors.initials: RH
authors.lastname: Larsen
mesh_terms: D000186:Actinium / Q000737:chemistry / Q000493:pharmacokinetics*; D000512:Alpha Particles; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism*; D005269:Femur / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics*; D013910:Thorium / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: C484243:(225)actinium-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-1,4,7,10-tetra(methylene)phosphonic acid; C484244:(227)thorium-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-1,4,7,10-tetra(methylene)phosphonic acid; C484245:(227)thorium-diethylene triamine N,N',N''-penta(methylene)phosphonic acid; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D019275:Radiopharmaceuticals; C042719:diethylenetriaminepenta(methylenephosphonic) acid; D013910:Thorium; C082084:1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylenephosphonic acid); D000186:Actinium