title: Synthesis and relaxometric characterization of a MRI Gd-based probe responsive to glutamic acid decarboxylase enzymatic activity.
abstract: Novel contrast agent based systems, which selectively visualize specific cells, e.g., neurons in the brain, would be of substantial importance for the fast developing field of molecular magnetic resonance imaging (MRI). We report here the synthesis and in vitro validation of a Gd(III)-based contrast agent designed to act as an MRI responsive probe for imaging the activity of the enzyme glutamic acid decarboxylase (GAD) present in neurons. Upon the action of the enzyme, the Gd(III) complex increases its hydration sphere and takes on a residual positive charge that promotes its binding to endogenous macromolecules. Both effects contribute in a synergic way to generate a marked relaxation enhancement, which directly reports enzyme activity and will allow activity detection of GAD positive cells in vitro and in vivo selectively.
authors.affiliation: Department of Molecular Biotechnologies and Health Sciences and Molecular Imaging Center, University of Torino, Turin, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Napolitano
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pariani
authors.forename: Franco
authors.initials: F
authors.lastname: Fedeli
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Baranyai
authors.forename: Markus
authors.initials: M
authors.lastname: Aswendt
authors.forename: Silvio
authors.initials: S
authors.lastname: Aime
authors.forename: Eliana
authors.initials: E
authors.lastname: Gianolio
mesh_terms: D060326:Chemistry Techniques, Synthetic; D003287:Contrast Media / Q000737:chemistry / Q000378:metabolism; D005682:Gadolinium / Q000737:chemistry* / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D015335:Molecular Probes / Q000737:chemistry / Q000378:metabolism; D009474:Neurons / Q000201:enzymology; D055672:Static Electricity
chemical_list: D003287:Contrast Media; D015335:Molecular Probes; D005682:Gadolinium; D005968:Glutamate Decarboxylase