Towards target-specific molecular imaging of angiogenesis with Gd-DTPA-based dendritic architectures

Dendritic MRI contrast agents are attractive candidates for mol. imaging of angiogenesis, since the multivalent dendritic architecture is an ideal mol. scaffold for constructing multiple MRI labels and target-specific markers on a single mol. Recently, different generation of the poly(propylene imine) dendrimers were functionalized with Gd-DTPA. The higher generations of these dendritic contrast agents display a pronounced enhancement of both the longitudinal and the transverse relaxivity compared to the parent Gd-DTPA complex. The kinetic physiol. properties of different generations dendritic contrast agents were investigated in mice at 1.5 T. Dynamic Contrast Enhanced Magnetic Resonance Angiog. expts. showed that the first generation dendritic MRI contrast agent was rapidly cleared by the renal system, while the fifth generation was cleared at significantly slower rate. Moreover, a Gd-DTPA complex functionalized with a target-specific oligopeptide for angiogenesis, the cyclic NGR motif, is prepd. and will be tested in vivo for MR imaging of angiogenesis. Conjugation of both target-specific peptides and MRI contrast agents on dendritic mols. may lead to an even larger improvement, both in binding as a result of multivalency and in terms of signal amplification.