In vivo characterization of a smart MRI agent that displays an inverse response to calcium concentration.
Contrast agents for magnetic resonance imaging (MRI) that exhibit sensitivity toward specific ions or molecules represent a challenging but attractive direction of research. Here a Gd(3+) complex linked to an aminobis(methylenephosphonate) group for chelating Ca(2+) was synthesized and investigated. The longitudinal relaxivity (r(1)) of this complex decreases during the relaxometric titration with Ca(2+) from 5.76 to 3.57 mM(-1) s(-1) upon saturation. The r(1) is modulated by changes in the hydration number, which was confirmed by determination of the luminescence emission lifetimes of the analogous Eu(3+) complex. The initial in vivo characterization of this responsive contrast agent was performed by means of electrophysiology and MRI experiments. The investigated complex is fully biocompatible, having no observable effect on neuronal function after administration into the brain ventricles or parenchyma. Distribution studies demonstrated that the diffusivity of this agent is significantly lower compared with that of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA).
Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics, Spemannstrasse 38, 72076 Tübingen, Germany.
Ilgar
I
Mamedov
Santiago
S
Canals
Jörg
J
Henig
Michael
M
Beyerlein
Yusuke
Y
Murayama
Hermann A
HA
Mayer
Nikos K
NK
Logothetis
Goran
G
Angelovski
D000818:Animals; D001923:Brain Chemistry; D002118:Calcium / Q000494:pharmacology*; D002413:Cations, Divalent / Q000494:pharmacology; D003287:Contrast Media / Q000008:administration & dosage / Q000032:analysis / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D004058:Diffusion; D004305:Dose-Response Relationship, Drug; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D007276:Injections, Intraventricular; D008279:Magnetic Resonance Imaging; D008297:Male; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D019906:Nuclear Magnetic Resonance, Biomolecular; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000032:analysis / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects; D014018:Tissue Distribution; D014867:Water
D002413:Cations, Divalent; D003287:Contrast Media; C582809:GDL contrast agent; D009942:Organometallic Compounds; D014867:Water; D019786:Gadolinium DTPA; D002118:Calcium