Exofacial protein thiols as a route for the internalization of Gd(III)-based complexes for magnetic resonance imaging cell labeling.
Four novel MRI Gd(III)-based probes have been synthesized and evaluated for their labeling properties on cultured cell lines K562, C6, and B16. The labeling strategy relies upon the fact that cells display a large number of reactive exofacial protein thiols (EPTs) that can be exploited as anchorage points for suitably activated MRI probes. The probes are composed of a Gd(III) chelate (based on either DO3A or DTPA) connected through a flexible linker to the 2-pyridyldithio chemical function for binding to EPTs. GdDO3A-based chelates could efficiently label cells (up to a level of 1.2 x 10(10) Gd(III) atoms/cell), whereas GdDTPA-based chelates showed poor or no cell labeling ability at all. Among the GdDO3A based compounds, that having the longest spacer (compound GdL1A) showed the best labeling efficacy. The mechanism of EPT mediated cell labeling by GdL1A involves probe internalization without sequestration of the Gd(III) chelate within subcellular structures such as endosomes.
Digilio
Giuseppe
G
Department of Environmental and Life Sciences, University of Eastern Piedmont "A. Avogadro", Viale T. Michel 11, I-15121 Alessandria, Italy.
Menchise
Valeria
V
Gianolio
Eliana
E
Catanzaro
Valeria
V
Carrera
Carla
C
Napolitano
Roberta
R
Fedeli
Franco
F
Aime
Silvio
S
D000818:Animals; D002614:Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D005682:Gadolinium / Q000737:chemistry*; D005910:Glioma / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics*; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D013056:Spectrophotometry, Ultraviolet; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism*
D002614:Chelating Agents; D003287:Contrast Media; D009942:Organometallic Compounds; D011506:Proteins; D013438:Sulfhydryl Compounds; D005682:Gadolinium