Magnetic resonance relaxivity of dendrimer‐linked nitroxides

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Abstract

The relaxivity and bioreduction rates of eight dendrimer-linked nitroxides varying in the number of nitroxides per molecule were measured and the potential use of these compounds as MR contrast agents was demonstrated. The T(1) and T(2) relaxivities, measured at room temperature and 1.5 T, varied linearly with the number of nitroxides per molecule for compounds with up to 16 nitroxides per molecule. Fourth-generation polypropylenimide- (DAB) and third-generation polyamidoamine- (PAMAM) dendrimer-linked nitroxides were found to have greater relaxivity than gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA). The greater number of nitroxides per dendrimer increased relaxivity over that of a single nitroxide, allowing a decreased dose to achieve differential contrast with MR evaluations. Rates of nitroxide bioreduction were below detection threshold using EPR spectroscopy for generation 2 dendrimers and higher. A pilot assessment of in vivo cartilage uptake that compared intraarticular injection of three structurally different dendrimer-linked nitroxides with Gd-DTPA and with saline demonstrated high affinity of the DAB-dendrimer-linked nitroxides for normal rabbit articular cartilage. From these results, it is evident that target-specific dendrimer-linked nitroxides can be designed.

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