Macromolecular MRI contrast agents for imaging tumor angiogenesis

Angiogenesis has long been accepted as a vital process in the growth and metastasis of tumors. As a result it is the target of several novel anti-cancer medications. Consequently, there is an urgent clinical need to develop accurate, non-invasive imaging techniques to improve the characterization of tumor angiogenesis and the monitoring of the response to anti-angiogenic therapy. Macromolecular MR contrast media (MMCM) offer this diagnostic potential by preferentially exploiting the inherent hyperpermeable nature of new tumor vessels compared with normal vessels. Over the last 10-15 years many classes of MMCM have been developed. When evaluated with dynamic contrast enhanced (DCE) MRI, a number of MMCM have demonstrated in vivo imaging properties that correlate with ex vivo histological features of angiogenesis. The enhancement patterns with some MMCM have been reported to correlate with tumor grade, as well as show response to anti-angiogenic and anti-vascular drugs. Future applications of MMCM include targeted angiogenesis imaging and drug delivery of anti-cancer 'payloads'. Herein we discuss the best known MMCMs along with their advantages and disadvantages.