The Development of an MR Agent for Imaging of Malignant Micro-calcification in Breast Cancer

Introduction We have been interested in developing multi-modality contrast agents that have high sensitivity and specificity for the imaging of hydroxyapatite (HA), which is the most common form of micro-calcifications found in human breast cancers [1]. Our approach is based on the observation that bisphosphonates, like pamidronate, show high affinity and high specificity for HA. We have previously reported an optical agent (near IR) [2], a SPECT agent, and a dual modality (NIR optical and SPECT) agent for imaging HA [3]. We have also developed analogous lanthanide-chelated DOTAbisphosphonate derivatives [4] that have high affinity and high selectivity for HA. Although, there have been a number of studies describing the synthesis and characterization of gadolinium based MR contrast agents targeted to imaging HA, their success has been limited to the extent that it has been suggested that binding to HA “silences” these agents through the removal of water from their hydration sphere upon binding to HA. In separate studies we have found that the water associated with HA crystals have a relatively long T1 and a short T2 indicating that these waters are out of the “extreme narrowing NMR limit” and thus may not be visualized on conventional MR sequences that have relatively long TE’s. In this present report we demonstrate the application of Ultra-short TE (UTE) sequences [5] for MR-imaging of contrast agents bound to HA in-vivo and in-vitro.