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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.

SUBMITTER: Harki DA

PROVIDER: S-EPMC2529060 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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

Harki Daniel A DA Satyamurthy Nagichettiar N Stout David B DB Phelps Michael E ME Dervan Peter B PB

Proceedings of the National Academy of Sciences of the United States of America 20080827 35

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. Smal ...[more]

PMID: 18753620

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