Preparation and characterization of a DOTA-lysine-biotin conjugate as an effector molecule for pretargeted radionuclide therapy

Bioconjug Chem. 2005 Nov-Dec;16(6):1468-74. doi: 10.1021/bc050188h.

Abstract

Pretargeted radionuclide therapy depends on the establishment of a high concentration of secondary binding sites at a tumor to which low-molecular weight radiolabeled effector molecules can be directed. This study describes the simple synthesis of an effector molecule and its subsequent characterization to determine the extent to which it complied with the ideal requirements of such a compound. (Epsilon)-DOTA-(alpha)-biotinamidolysine (DLB) was synthesized in high yield and purity using conventional SPPS methodology. High radiochemical purities were obtained when labeled with several potentially useful radionuclides. The radiolabeled analogue bound to streptavidin efficiently with a stoichiometry similar to that of native biotin and showed high stability in serum and upon challenge with acid conditions. Biodistribution studies in normal animals showed a rapid rate of clearance from the blood and low retention of radioactivity by normal tissues. This design of effector molecule therefore shows promise for further pretargeted radionuclide therapy studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biotin / analogs & derivatives*
  • Biotin / chemical synthesis
  • Biotin / pharmacokinetics
  • Drug Stability
  • Indium Radioisotopes
  • Lysine
  • Metabolic Clearance Rate
  • Mice
  • Mice, Inbred BALB C
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / pharmacokinetics*
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / pharmacokinetics
  • Radiopharmaceuticals / therapeutic use
  • Streptavidin
  • Tissue Distribution

Substances

  • DOTA-biotin
  • Indium Radioisotopes
  • Organometallic Compounds
  • Radiopharmaceuticals
  • Biotin
  • Streptavidin
  • Lysine