title: Innovative Design of Ca-Sensitive Paramagnetic Liposomes Results in an Unprecedented Increase in Longitudinal Relaxivity.
abstract: Bioresponsive MRI contrast agents sensitive to Ca(II) fluctuations may play a critical role in the development of functional molecular imaging methods to study brain physiology or abnormalities in muscle contraction. A great challenge in their chemistry is the preparation of probes capable of inducing a strong signal variation that could be detected in a robust way. To this end, the incorporation of small molecular weight bioresponsive agents into nanocarriers can improve the overall properties in a few ways: (i) the agent can be delivered into the tissue of interest, increasing the local concentration; (ii) its biokinetic properties and retention time will improve; (iii) the high molecular weight and size of the nanocarrier may cause additional changes in the MRI signal and raise the chances for their detection in functional experiments. In this work, we report the preparation of the new class of liposome-based, Ca-sensitive MRI agents. We synthesized a novel amphiphilic ligand which was incorporated into the liposome bilayer. A remarkable increase of ∼420% in longitudinal relaxivity r1, from 7.3 mM(-1) s(-1) to 38.1 mM(-1) s(-1) at 25 °C and 21.5 MHz in the absence and presence of Ca(II), respectively, was achieved by the most active liposomal formulation. To the best of our knowledge, this is the highest change in r1 observed for Ca-sensitive agents at physiological pH and can be explained by simultaneous Ca-triggered increase in hydration and reduction of local motion of Gd(III) complex, which can be followed at low magnetic fields.
authors.affiliation: Molecular & Preclinical Imaging Centers, Department of Molecular Biotechnology and Health Sciences, University of Torino , Via Nizza 52, 10126 Torino, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Garello
authors.affiliation: Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics , 72076 Tübingen, Germany.
authors.forename: Sandip
authors.initials: S
authors.lastname: Vibhute
authors.affiliation: MR Neuroimaging Agents, Max Planck Institute for Biological Cybernetics , Spemannstrasse 41, 72076 Tübingen, Germany.
authors.forename: Serhat
authors.initials: S
authors.lastname: Gündüz
authors.affiliation: Physiology of Cognitive Processes, Max Planck Institute for Biological Cybernetics , 72076 Tübingen, Germany.|Department of Imaging Science and Biomedical Engineering, University of Manchester , Manchester M13 9PT, United Kingdom.
authors.forename: Nikos K
authors.initials: NK
authors.lastname: Logothetis
authors.affiliation: Molecular & Preclinical Imaging Centers, Department of Molecular Biotechnology and Health Sciences, University of Torino , Via Nizza 52, 10126 Torino, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Terreno
authors.affiliation: MR Neuroimaging Agents, Max Planck Institute for Biological Cybernetics , Spemannstrasse 41, 72076 Tübingen, Germany.
authors.forename: Goran
authors.initials: G
authors.lastname: Angelovski
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry; D002118:Calcium / Q000737:chemistry; D003287:Contrast Media / Q000737:chemistry*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D008279:Magnetic Resonance Imaging / Q000379:methods*
chemical_list: D001672:Biocompatible Materials; D003287:Contrast Media; D004337:Drug Carriers; D008081:Liposomes; D005682:Gadolinium; D002118:Calcium