PuSH - Publication Server of Helmholtz Zentrum München

Gottschalk, S. ; Engelmann, J.* ; Rolla, G.A.* ; Botta, M.* ; Parker, D.* ; Mishra, A.

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

Org. Biomol. Chem. 11, 6131-6141 (2013)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
Altmetric
Additional Metrics?
[➜Log in]
Edit extra informations Login
Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 1477-0520
e-ISSN 1477-0539
Journal Organic & Biomolecular Chemistry
Quellenangaben Volume: 11, Issue: 36, Pages: 6131-6141 Article Number: , Supplement: ,
Publisher Royal Society of Chemistry (RSC)
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Biological and Medical Imaging (IBMI)