Endocrine Abstracts

Major clinical events such as myocardial infarction and stroke are caused by atherosclerosis, a lipid-driven chronic inflammatory disease affecting the arterial wall. In recognition of the inflammatory drive in cardiovascular disease (CVD), a major interest has risen to complement current standards for high-risk patients by therapeutically targeting the inflammatory process. Prior to clinical application, therapeutic candidates are required to have a robust anti-inflammatory effect without affecting systemic immunity. Local delivery of drugs via nanomedicine offers the advantage of enhancing local drug accumulation at target sites, while decreasing systemic exposure. In fact, several nanotherapeutical formulations of anticancer and anti-inflammatory drugs have been approved for clinical use based upon their improved balance of efficacy versus toxicity. Nevertheless, the efforts to promote alternative local delivery modalities in CVD has lagged behind. Part of the reluctance in CVD pertains to the notion that the atherosclerotic lesion represents a poorly perfused compartment with low accessibility for therapeutic compounds. More recently, however, we have shown that the atherosclerotic lesions in humans can be targeted, provided that the compound has a prolonged plasma half-life allowing for sufficient time to extravasate into the atherosclerotic lesion. To evaluate the local efficacy of nanomedicinal compunds at the level of the artieral wall, several emerging non-invasive imaging modalities, including PET/CT and DCE-MRI, can serve as surrogate imaging markers in relatively small-scaled clinical trials.