High-performance hepatobiliary dysprosium contrast agent for ultra-high-field magnetic resonance imaging

Ultra-high-field (UHF) magnetic resonance imaging (MRI) can open up new avenues in clinical diagnostic imaging. Its sensitivity can be further improved using contrast agents (CAs). Therefore, developing low-molecular-weight MR CAs that are efficient under UHF is crucial to ensure taking full advantage of MR imaging at UHF. Moreover, designing highly stable UHF liver-specific CA has been challenging. Here, using dysprosium (Dy3+), which relaxes water protons via a Curie relaxation that increases T2 relaxation substantially with the magnetic field strength, we report a new macrocyclic liver specific Dy3+ complex (Dy[DO3A-EOB]). We observed a 7.06 times higher r2/r1 ratio of Dy[DO3A-EOB] at 9.4T than that of 1.5T, which suggests a superior negative-enhancing MR CA at UHF. In vivo MR imaging results further demonstrated that Dy[DO3A-EOB] showed a much strong negative enhancement at UHF (9.4T) than under a low field (1.5T). It was also found that, in addition to the ligand structure, the metal itself plays an important role in determining the liver uptake pattern of the CA. Therefore, we successfully demonstrated the first example of a small-molecular-weight liver-specific Dy3+ complex acting as a T2 CA with high sensitivity at UHF for diagnosis of liver diseases.