Synthesis and relaxometric studies of a dendrimer-based pH-responsive MRI contrast agent

M. Meser Ali, Mark Woods, Peter Caravan, Ana C L Opina, Marga Spiller, James C. Fettinger, A. Dean Sherry

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

The design of effective pH responsive MRI contrast agents is a key goal in the development of new diagnostic methods for conditions such as kidney disease and cancer. A key factor determining the effectiveness of an agent is the difference between the relaxivity of the "on" state compared to that of the "off" state. In this paper, we demonstrate that it is possible to improve the pH-responsive action of a low molecular weight agent by conjugating it to a macromolecular construct. The synthesis of a bifunctional pH responsive agent is reported. As part of that synthetic pathway we examine the Ing-Manske reaction, identifying an undesirable by-product and establishing effective conditions for promoting a clean and effective reaction. Reaction of the bifunctional pH responsive agent with a G5-PAMAM dendrimer yielded a product with an average of 96 chelates per dendrimer. The relaxivity of the dendrimer conjugate rises from 10.8 mM-1s-1 (pH 9) to 24.0 mM -1 s-1 (pH 6) per Gd3+ ion. This more than doubles the relaxivity pH response, Δr1, of our agent from just 51% for the original low molecular weight chelate to 122% for the dendrimer.

Original languageEnglish (US)
Pages (from-to)7250-7258
Number of pages9
JournalChemistry - A European Journal
Volume14
Issue number24
DOIs
StatePublished - Aug 18 2008

Keywords

  • Dendrimers
  • Imaging agents
  • Lanthanide complexes
  • MRI contrast agents

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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