A convenient methodology has been developed for the synthesis of gadolinium−diethylenetriaminepentaacetic acid (Gd−DTPA)-terminated poly(propylene imine) dendrimers as contrast agents for magnetic resonance imaging (MRI). In our strategy, isocyanate-activated, tert-butyl-protected DTPA analogues were coupled to different generations of poly(propylene imine) dendrimers. Deprotection of the tert-butyl esters with trifluoroacetic acid in dichloromethane and extensive dialysis afforded gadolinium-chelating poly(propylene imine) dendrimers. The corresponding Gd−DTPA-based dendritic contrast agents were prepared from GdCl3 in either water or citrate buffer. Atomic force microscopy and cryogenic transmission electron microscopy experiments of the fifth-generation Gd−DTPA based dendritic contrast agent in citrate buffer demonstrated the presence of well-defined spherical particles with nanoscopic dimensions (5−6 nm), and no self-aggregation of dendrimers was observed. The efficiencies of these dendritic contrast ...