Thorium and Actinium Polyphosphonate Compounds as Bone-Seeking Alpha Particle-Emitting Agents

Anticancer Res. Jan-Feb 2004;24(1):101-5.

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.

MeSH terms

  • Actinium / chemistry
  • Actinium / pharmacokinetics*
  • Alpha Particles
  • Animals
  • Bone and Bones / metabolism*
  • Femur / metabolism
  • Kidney / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Organometallic Compounds / pharmacokinetics*
  • Organophosphorus Compounds / chemistry
  • Organophosphorus Compounds / pharmacokinetics
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacokinetics*
  • Thorium / chemistry
  • Thorium / pharmacokinetics*
  • Tissue Distribution

Substances

  • (225)actinium-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-1,4,7,10-tetra(methylene)phosphonic acid
  • (227)thorium-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-1,4,7,10-tetra(methylene)phosphonic acid
  • (227)thorium-diethylene triamine N,N',N''-penta(methylene)phosphonic acid
  • Organometallic Compounds
  • Organophosphorus Compounds
  • Radiopharmaceuticals
  • diethylenetriaminepenta(methylenephosphonic) acid
  • Thorium
  • 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrakis(methylenephosphonic acid)
  • Actinium