Anaerobic 90Y- and 177Lu-labeling of a DOTA-conjugated nonpeptide vitronectin receptor antagonist

Bioconjug Chem. 2003 Sep-Oct;14(5):1030-7. doi: 10.1021/bc020061h.

Abstract

This study describes the discovery and development of an anaerobic formulation for the routine preparation of (90)Y and (177)Lu complexes ((90)Y-TA138 and (177)Lu-TA138) of a DOTA-conjugated nonpeptide vitronectin receptor antagonist (TA138: 3-sulfon-N-[[4,7,10-tris(carboxymethyl)1,4,7,10-tetraazacyclododec-1-yl]acetyl]-l-alanyl-N-[2-[4-[[[(1S)-1-carboxy-2[[[1,4-dihydro-7-[(1H-imidazol-2-ylamino]meth-yl]-1-methyl-4-oxo-3-quinolinyl]carbonyl]amino]ethyl]amino]-sulfonyl]-3,5-dimethylphenoxy]-1-oxobutyl]amino]ethyl]-3-sulfo-l-alaninamide). Since (90)Y-TA138 and (177)Lu-TA138 are very sensitive to radiolytic degradation, exclusion of oxygen is necessary during the radiolabeling. Using the anaerobic formulation, (90)Y-TA138 and (177)Lu-TA138 can be prepared in high yield and high specific activity. The anaerobic formulation described in this study is particularly useful for (90)Y- and (177)Lu-labeling of DOTA-conjugated small biomolecules, which are sensitive to the radiolytic degradation during radiolabeling.

MeSH terms

  • Biotin / analogs & derivatives*
  • Biotin / chemistry
  • Biotin / pharmacokinetics
  • Bombesin / chemistry
  • Bombesin / pharmacokinetics
  • Integrin alphaVbeta3 / antagonists & inhibitors*
  • Lutetium / chemistry*
  • Lutetium / pharmacokinetics
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacokinetics
  • Peptide Fragments / chemistry
  • Peptide Fragments / pharmacokinetics
  • Radioisotopes / chemistry*
  • Radioisotopes / pharmacokinetics
  • Technology, Pharmaceutical / methods
  • Yttrium Radioisotopes / chemistry*
  • Yttrium Radioisotopes / pharmacokinetics

Substances

  • 177Lu-DOTA-8-aminooctanoylbombesin (7-14)-amide
  • DOTA-biotin
  • Integrin alphaVbeta3
  • Organometallic Compounds
  • Peptide Fragments
  • Radioisotopes
  • Yttrium Radioisotopes
  • Lutetium
  • Biotin
  • Bombesin