Abstract: MRI sensitivity for diagnosis and localization of early myocarditis is limited, although it is of central clinical interest. The aim of this project was to test a contrast agent targeting activated platelets consisting of microparticles of iron oxide (MPIO) conjugated to a single-chain antibody directed against ligand-induced binding sites (LIBS) of activated glycoprotein IIb/IIIa (= LIBS-MPIO). Myocarditis was induced by subcutaneous injection of an emulsion of porcine cardiac myosin and complete Freund's adjuvant in mice. 3D 7 T in-vivo MRI showed focal signal effects in LIBS-MPIO injected mice 2 days after induction of myocarditis, whereas in control-MPIO injected mice no signal was detectable. Histology confirmed CD41-positive staining, indicating platelet involvement in myocarditis in mice as well as in human specimens with significantly higher LIBS-MPIO binding compared to control-MPIO in both species. Quantification of the myocardial MRI signal confirmed a signal decrease after LIBS-MPIO injection and significant less signal in comparison to control-MPIO injection. These data show, that platelets are involved in inflammation during the course of myocarditis in mice and humans. They can be imaged non-invasively with LIBS-MPIO by molecular MRI at an early time point of the inflammation in mice, which is a valuable approach for preclinical models and of interest for both diagnostic and prognostic purposes

Abstract: Advances in diagnostic imaging have provided unprecedented opportunities to detect diseases at early stages and with high reliability. Diagnostic imaging is also crucial to monitoring the progress or remission of disease and thus is often the central basis of therapeutic decision-making. Currently, several diagnostic imaging modalities (computed tomography, magnetic resonance imaging, and positron emission tomography, among others) are routinely used in clinics and present their own advantages and limitations. In vivo near-infrared (NIR) fluorescence imaging has recently emerged as an attractive imaging modality combining low cost, high sensitivity, and relative safety. As a preclinical tool, it can be used to investigate disease mechanisms and for testing novel diagnostics and therapeutics prior to their clinical use. However, the limited depth of tissue penetration is a major challenge to efficient clinical use. Therefore, the current clinical use of fluorescence imaging is limited to a few applications such as image-guided surgery on tumors and retinal angiography, using FDA-approved dyes. Progress in fluorophore development and NIR imaging technologies holds promise to extend their clinical application to oncology, cardiovascular diseases, plastic surgery, and brain imaging, among others. Nanotechnology is expected to revolutionize diagnostic in vivo fluorescence imaging through targeted delivery of NIR fluorescent probes using antibody conjugation. In this review, we discuss the latest advances in in vivo fluorescence imaging technologies, NIR fluorescent probes, and current and future clinical applications