Conjugation of DOTA using isolated phenolic active esters: the labeling and biodistribution of albumin as blood pool marker

Bioconjug Chem. 2005 Jan-Feb;16(1):237-40. doi: 10.1021/bc034216c.

Abstract

A convenient method for the functionalization of proteins with DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) has been developed. For this purpose DOTA was converted into a series of different monoreactive activated phenolic esters. The esters were prepared in a single step from commercially available DOTA, using 1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide or 1,3-dicyclohexylcarbodiimide as coupling agent. The resulting activated esters were isolated by HPLC, lyophilized, and stored for future applications. In solid form the compounds exhibit high hydrolytic stability. The reactions with proteins proceeded in good yields. The conjugation and subsequent radiolabeling of the 4-nitrophenol ester of DOTA with 67Ga was investigated with rat serum albumin. A time-dependent biodistribution study in tumor bearing rats was conducted to demonstrate the integrity of the albumin conjugate. These results suggest that phenolic esters of DOTA represent versatile reagents to conjugate DOTA with proteins and other biomolecules in high yields.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Albumins / chemistry
  • Albumins / metabolism*
  • Animals
  • Biomarkers
  • Blood / metabolism*
  • Esters / chemistry*
  • Esters / isolation & purification
  • Heterocyclic Compounds, 1-Ring / chemistry*
  • Isotope Labeling
  • Magnetic Resonance Spectroscopy
  • Nitrophenols / chemistry
  • Phenols / chemistry*
  • Rats
  • Time Factors
  • Tissue Distribution

Substances

  • Albumins
  • Biomarkers
  • Esters
  • Heterocyclic Compounds, 1-Ring
  • Nitrophenols
  • Phenols
  • 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
  • 4-nitrophenol