Improved in vivo stability of actinium-225 macrocyclic complexes

J Med Chem. 1999 Jul 29;42(15):2988-92. doi: 10.1021/jm990141f.

Abstract

The favorable nuclear properties of actinium-225 ((225)Ac) have led to proposal of this isotope for use in radioimmunotherapy. In an effort to reduce the toxicity of free (225)Ac, a series of ligands were evaluated for stability in vivo. Loss of (225)Ac from acyclic chelating agents resulted in high liver uptake and poor whole body clearance. The macrocyclic ligands c-DOTA, PEPA, and HEHA were evaluated, and (225)Ac-HEHA showed exceptional stability in vivo. (225)Ac chelated with EDTA, DTPA, DOTA, or PEPA permitted substantial accumulation of the radionuclide to the liver, while the (225)Ac-HEHA complex was essentially excreted within minutes of administration. The preparation of the ligands and radiolabeled complexes and the biodistribution results will be discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetates / chemical synthesis*
  • Acetates / chemistry
  • Acetates / pharmacokinetics
  • Actinium*
  • Animals
  • Chelating Agents / chemical synthesis*
  • Chelating Agents / chemistry
  • Drug Stability
  • Female
  • Ligands
  • Mice
  • Mice, Inbred BALB C
  • Organometallic Compounds / chemical synthesis*
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacokinetics
  • Radioisotopes*
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacokinetics
  • Tissue Distribution

Substances

  • Acetates
  • Chelating Agents
  • Ligands
  • Organometallic Compounds
  • Radioisotopes
  • Radiopharmaceuticals
  • actinium 1,4,7,10,13,16-hexaazacyclohexadecane-N,N',N'',N''',N'''',N'''''-hexaacetic acid
  • Actinium