title: In vivo imaging of pyrrole-imidazole polyamides with positron emission tomography.
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 (18)F-radiolabeled polyamides were prepared by oxime ligation between 4-[(18)F]-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 beta-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.
authors.affiliation: Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Harki
authors.forename: Nagichettiar
authors.initials: N
authors.lastname: Satyamurthy
authors.forename: David B
authors.initials: DB
authors.lastname: Stout
authors.forename: Michael E
authors.initials: ME
authors.lastname: Phelps
authors.forename: Peter B
authors.initials: PB
authors.lastname: Dervan