Preliminary evaluation of PARACEST MRI agents for the detection of nitric oxide synthase

Authors

Mojmír Suchý, The University of Western Ontario
Alex X. Li, Robarts Research Institute
Yin Liu, The University of Western Ontario
Qingping Feng, The University of Western Ontario
Robert Bartha, Robarts Research InstituteFollow
Robert H.E. Hudson, The University of Western Ontario

Document Type

Article

Publication Date

1-1-2016

Journal

Canadian Journal of Chemistry

Volume

94

Issue

8

First Page

715

Last Page

722

URL with Digital Object Identifier

10.1139/cjc-2016-0179

Abstract

Several paramagnetic chemical exchange saturation transfer magnetic resonance imaging (PARACEST MRI) agents for the potential detection of nitric oxide synthase (NOS) have been synthesized and evaluated. These agents are based on an amino acid-or dipeptide-decorated DOTAM (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid amide) chelator possessing either Tm3+ or Dy3+. The amino acid and dipeptide decorated DOTAMs were designed such that the terminal amino acid pendant group was l-arginine, which may be converted to l-citrulline by NOS. Preliminary evaluation has revealed that some of the l-arginine-decorated complexes are recognized and metabolized by the NOS. Differences in the CEST properties between Dy3+-metallated l-arginine-and l-citrulline-modified complexes suggest that these might be suitable for imaging of the NOS enzymatic activity.