title: A tripodal ruthenium-gadolinium metallostar as a potential α(v)β(3) integrin specific bimodal imaging contrast agent.
abstract: Gd(III)-containing metallostar contrast agents are gaining increased attention, because their architecture allows for a slower tumbling rate, which, in turn, results in larger relaxivities. So far, these metallostars find possible applications as blood pool contrast agents. In this work, the first example of a tissue-selective metallostar contrast agent is described. This RGD-peptide decorated Ru(II)(Gd(III))(3)metallostar is synthesized as an α(v)β(3)-integrin specific contrast agent, with possible applications in the detection of atherosclerotic plaques and tumor angiogenesis. The contrast agent showed a relaxivity of 9.65 s(-1) mM(-1), which represents an increase of 170%, compared to a low-molecular-weight analogue, because of a decreased tumbling rate (τ(R) = 470 ps). The presence of the MLCT band (absorption 375-500 nm, emission 525-850 nm) of the central Ru(II)(Ph-Phen)(3)-based complex grants the metallostar attractive luminescent properties. The (3)MLCT emission is characterized by a quantum yield of 4.69% and a lifetime of 804 ns, which makes it an interesting candidate for time-gated luminescence imaging. The potential application as a selective MRI contrast agent for α(v)β(3)-integrin expressing tissues is shown by an in vitro relaxometric analysis, as well as an in vitroT(1)-weighted MR image.
authors.affiliation: University of Leuven, Department of Chemistry, Celestijnenlaan 200F-P.O. Box 2404, B-3001 Heverlee, Belgium.
authors.forename: Peter
authors.initials: P
authors.lastname: Verwilst
authors.forename: Svetlana V
authors.initials: SV
authors.lastname: Eliseeva
authors.forename: Luce
authors.initials: L
authors.lastname: Vander Elst
authors.forename: Carmen
authors.initials: C
authors.lastname: Burtea
authors.forename: Sophie
authors.initials: S
authors.lastname: Laurent
authors.forename: Stéphane
authors.initials: S
authors.lastname: Petoud
authors.forename: Robert N
authors.initials: RN
authors.lastname: Muller
authors.forename: Tatjana N
authors.initials: TN
authors.lastname: Parac-Vogt
authors.forename: Wim M
authors.initials: WM
authors.lastname: De Borggraeve
mesh_terms: D003287:Contrast Media / Q000737:chemistry*; D005682:Gadolinium / Q000737:chemistry*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000032:analysis*; D019169:Jurkat Cells; D049408:Luminescent Agents / Q000737:chemistry; D008279:Magnetic Resonance Imaging; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*
chemical_list: D003287:Contrast Media; D039302:Integrin alphaVbeta3; D049408:Luminescent Agents; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D012428:Ruthenium; D005682:Gadolinium