In vivo imaging of pyrrole-imidazole polyamides with positron emission tomography

Daniel A. Harki, Nagichettiar Satyamurthy, David B. Stout, Michael E. Phelps, Peter B. Dervan

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

The biodistribution profiles in mice of two pyrrole-imidazole polyamides were determined by PET. Pyrrole-imidazole polyamides are a class of small molecules that can be programmed to bind a broad repertoire of DNA sequences, disrupt transcription factor-DNA interfaces, and modulate gene expression pathways in cell culture experiments. The 18F-radiolabeled polyamides were prepared by oxime ligation between 4-[18F]-fluorobenzaldehyde and a hydroxylamine moiety at the polyamide C terminus. Small animal PET imaging of radiolabeled polyamides administered to mice revealed distinct differences in the biodistribution of a 5-ring β-linked polyamide versus an 8-ring hairpin, which exhibited better overall bioavailability. In vivo imaging of pyrrole-imidazole polyamides by PET is a minimum first step toward the translation of polyamide-based gene regulation from cell culture to small animal studies.

Original languageEnglish (US)
Pages (from-to)13039-13044
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number35
DOIs
StatePublished - Sep 2 2008

Keywords

  • Biodistribution
  • Fluorine-18
  • Oxime
  • Radiosynthesis

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