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The emerging field of "molecular imaging" refers to in vivo diagnosis of complex pathological processes by specific detection of unique molecular signatures of disease states either at the cellular, subcellular, or gene level. Identification of specific molecular epitopes causally associated with pathologies can be accomplished with the use of various novel targeted contrast agents, which permit conjunctive delivery and local deposition of therapeutic agents directly at the site of disease. Combining imaging with drug delivery provides verification of drug delivery and quantification of treatment, serving in effect as a new paradigm for rational drug dosing. Important potential clinical applications for targeted contrast agents include: (1) characterization of vulnerable plaques by detection of microscopic deposits of fibrin in plaque fissures prior to rupture. (2) early detection and treatment of solid tumors and metastases (colon, breast, prostate, etc.) by localization of angiogenesis. (3) detection of early atherosclerosis by assessment of epitopes related to macrophage trafficking (e.g., VCAM), and (4) diagnosis and treatment of inflammatory pathologies (infection, arthritis, myocarditis, transplant rejection, etc.) by delineation of epitopes that are markers for inflammatory cell recruitment (adhesion molecules, selectins, etc.) We provide a brief review of the field and discuss specific applications.

Molecular imaging with targeted contrast agents is emerging as an important technological advance for diagnostic ultrasound. In vivo, these agents must bind to and acoustically enhance their targets before the agents are cleared or destroyed. In this study, we present results using a system that was designed and constructed for visualization of the evolution of acoustic contrast enhancement. To evaluate the system, two targets were examined: avidin-complexed nitrocellulose membrane and human plasma clots. The time evolution of enhancement was visualized in 10-minute increments for one hour. A monotonic increase was observed in ultrasonic reflection enhancement from specially treated nitrocellulose membranes for targeted emulsions containing perfluorooctylbromide (1.3/spl plusmn/0.3 dB) and perfluorooctane (2.6/spl plusmn/0.5 dB) within the first 60 minutes of imaging. In comparison, the inherently non-echogenic plasma clots showed a substantial increase of 12.0/spl plusmn/0.9 dB when targeted with a perfluorooctane emulsion. This study demonstrates the concept of molecular imaging and provides the first quantifiable time evolution report of the binding of a site-targeted ultrasonic contrast agent.

Improved echocardiographic endocardial border delineation aids in the assessment of ventricular function and wall motion abnormalities. Microbubble-based contrast agents provide excellent echogenicity but a short-lived effect. In contrast, liquid perfluorocarbon (PFC) nanoparticles exhibit long circulatory times and are stable to insonification but have poor echogenicity. Ideally, a contrast agent should demonstrate long circulatory persistence, resistance to ultrasonic destruction, while displaying significant echogenicity. This study demonstrates the effectiveness of biocompatible, liquid PFC nanoparticles as a blood pool contrast agent. When imaged with power Doppler harmonic imaging (PDHI), this agent exhibited marked blood pool enhancement lasting over 1 hour. Furthermore, the contrast enhancement was achieved at doses of 0.7% blood volume. In order to investigate the influence of particle size on blood pool contrast effect, liquid PFC nanoparticles were formulated with diameters of 232 and 465 nm. The nanoparticles were then administered to canines (N=10), with 7 canines receiving the 232 nm nanoparticles and the remainder receiving the 465 nm nanoparticles at a dose of 0.5 ml/kg. PDHI revealed marked blood pool enhancement in all three canines receiving the 465 nm nanoparticles but minimal contrast effect in the canines receiving the 232 nm nanoparticles. This data suggests that PFC nanoparticles in conjunction with PDHI may serve as an important adjunct for the assessment of ventricular function and wall motion abnormalities.