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Advances in molecular biology and cellular biochemistry are providing new opportunities for diagnostic medical imaging. Molecular imaging provides an opportunity to "see" the earliest biochemical signatures of disease in vivo analogous to microscopic detection of epitopes with immunohistochemistry techniques. Previously the province of nuclear medicine, today numerous, highly active research programs can be found for all clinically relevant imaging modalities. In many instances, these emerging site-directed imaging agents also incorporate therapeutic agents for drug delivery, allowing noninvasive confirmation and quantification of the targeted therapeutic dose. We have developed a novel multi-modal site-targeted contrast agent for sensitive and specific imaging of molecular epitopes and local therapy, which illustrates the key features of these emerging platform technologies. Targeted nanoparticles are applicable to ultrasound, nuclear, CT, and magnetic resonance imaging and have been used to detect a variety of epitopes expressed on angiogenic vessels, thrombus, and within vascular walls. Moreover, this particular targeted agent can deposit a therapeutic payload through a unique mechanism termed "contact-facilitated delivery". The combined benefits of molecular imaging and therapeutic systems are merging and will potentially alter many current clinical paradigms in the next decade.