MR molecular imaging of angiogenesis using targeted perfluorocarbon nanoparticles.

Molecular imaging is defined as the in vivo diagnosis of complex pathological processes by detection of unique biological signatures at the sub-cellular level. To accomplish this, specialized imaging agents are required that accumulate at the site of interest and bring enough “payload” with them to be detected via magnetic resonance imaging. Molecular imaging with perfluorocarbon nanoparticles has matured significantly during recent years. Experiments in a rabbit model have shown its potential to image angiogenesis, which is an early marker of disease, quantifying the extent and distribution of biomarkers to characterize tumors and predict and monitor the response to therapy. As we continue to broaden our attention to the complete cycle of care for patients, the concept of individualized care becomes increasingly important, driving a paradigm shift leading toward personalized medicine [1]. Some newly-developed therapies are extremely potent and highly specific at treating disease, e.g. cancer; but they require detailed and precise patient stratification. Given the vast diversity of pathology, a particular targeted therapy can help only a selected sub-group of patients whose disease expresses a specific molecular target. As the therapy side effects may be severe and targeted therapies are expensive, molecular imaging (MI) based stratification opens the way to reduce unnecessary risk to patients, while also helping to manage the associated healthcare costs. Furthermore, direct combination of MI techniques and novel therapeutic nanoparticles (i.e. “theranostics”) may provide a means to characterize disease, confirm and quantify therapy delivery, and monitor the response (or lack thereof) to therapy serially and noninvasively. In 2003, a special issue of Medicamundi was devoted to “Molecular Imaging: The Road Ahead” [2] covering a large spectrum of molecular imaging modalities (from Nuclear Medicine to High Intensity Focused Ultrasound), in which we contributed results and an outlook on applications of magnetic resonance (MR) imaging using targeted imaging agents [3]. In the present article, we review where this road has led in the past years, in particular in the field of molecular imaging and targeted therapy based on site-targeted, paramagnetic, perfluorocarbon (PFC) nanoparticles in combination with water- and fluorine-based MR imaging. After a brief recapitulation of the original article, we cover state-of-the art applications in imaging and quantification of angiogenesis by means of pre-clinical examples as well as insights into the role of MR in therapy solutions.