Jump to main content
Jump to site search

Issue 36, 2013
Previous Article Next Article

Comparative in vitro studies of MR imaging probes for metabotropic glutamate subtype-5 receptor targeting

Author affiliations

Abstract

A series of magnetic resonance imaging probes has been evaluated to target selectively the metabotropic glutamate receptor subtype 5 (mGluR5). Eight imaging probes based on the contrast agent [Gd·DOTA], previously derived by linking it to a series of specific and selective mGluR5 antagonists, have been extensively tested for their functionality in vitro. The Nuclear Magnetic Relaxation Dispersion (NMRD) profiles of selected probes have been examined via field-cycling relaxometry in the presence and absence of a model protein. The properties of the targeted contrast agents were evaluated using a primary astrocyte model, as these cells mimic the in vivo situation effectively. The probes were non-toxic (up to 200 μM) to these mGluR5 expressing primary cells. Cellular proton longitudinal relaxation rate enhancements of up to 35% were observed by MRI at 200 μM of probe concentration. The antagonistic effect of all compounds was tested using an assay measuring changes of intracellular calcium levels. Furthermore, treatment at two different temperatures (4 °C vs. 37 °C) and of an mGluR5-negative cell line provided further insight into the selectivity and specificity of these probes towards cell surface mGluR5. Finally, two out of eight probes demonstrated an antagonistic effect as well as significant enhancement of receptor mediated cellular relaxation rates, strongly suggesting that they would be viable probes for the mapping of mGluR5 by MRI in vivo.

Graphical abstract: Comparative in vitro studies of MR imaging probes for metabotropic glutamate subtype-5 receptor targeting

Back to tab navigation

Supplementary files

Publication details

The article was received on 24 Jun 2013, accepted on 22 Jul 2013 and first published on 23 Jul 2013


Article type: Paper
DOI: 10.1039/C3OB41297K
Citation: Org. Biomol. Chem., 2013,11, 6131-6141
  •   Request permissions

    Comparative in vitro studies of MR imaging probes for metabotropic glutamate subtype-5 receptor targeting

    S. Gottschalk, J. Engelmann, G. A. Rolla, M. Botta, D. Parker and A. Mishra, Org. Biomol. Chem., 2013, 11, 6131
    DOI: 10.1039/C3OB41297K

Search articles by author

Spotlight

Advertisements