A Tripodal Ruthenium-Gadolinium Metallostar as a Potential a(v)ß(3) Integrin Specific Bimodal Imaging Contrast Agent

GdIII-containing metallostar contrast agents are gaining increased attention, since 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 RuII(GdIII)3 metallostar is synthesized as an avß3-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-1mM-1, which represents an increase of 170% compared to a low molecular weight analogue, due to a decreased tumbling rate (tR = 470 ps). The presence of the MLCT band (absorption 375-500 nm, emission 525-850 nm) of the central RuII(Ph-Phen)3-based complex, grants the metallostar attractive luminescent properties. The 3MLCT 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 avß3-integrin expressing tissues is shown by an in vitro relaxometric analysis as well as an in vitro T1-weighted MR image.