Influence of human serum albumin on longitudinal and transverse relaxation rates (R1 and R2) of magnetic resonance contrast agents

Objectives: Exogenous magnetic resonance (MR) contrast media (CM) are used to improve detection and delineation of physiological and pathologic structures. Temporary binding between CM and proteins such as human serum albumin (HSA) may alter the relaxation-enhancing properties of specific contrast agents. In this study, the presence and strength of HSA interaction with different CM was investigated. Material and Methods: Three contrast agents were chosen: GdDTPA, Gd-BT-DO3A, and Gd-BOPTA, each of which is known to have a different protein interaction. Samples were prepared using 7 different HSA concentrations, all at a constant CM concentration of 0.5 mmol/L. The relaxation rates, R1 and R2, of each sample were measured at 1.5 T. Virtual docking studies were performed to estimate the number of high affinity-binding sites of Gd-BOPTA and the surface of the HSA dimer. Results: Gd-BOPTA caused the greatest increase in R1 and R2, which followed an exponential dependency with increasing HSA concentration. Between the range of 0 and 7 g/dL of HSA, GdDTPA and Gd-BT-DO3A showed a relative change in both relaxation rates of approximately 13% and 22% for R1 and 26% and 30% for R2, respectively. In contrast, Gd-BOPTA demonstrated a relative increase of approximately 108% and 363% for R1 and R2, respectively. Changes of HSA concentration within physiological range (3.5-5.5 g/dL) resulted in an increase of RI and R2 of approximately 40% when using Gd-BOPTA. The docking study revealed that approximately 10 small hydrophobic pockets exist on the HSA surface where the aromatic tail of Gd-BOPTA can fit in and a stronger noncovalent binding can occur compared with Gd-DTPA and Gd-BT-DO3A. Conclusion: Relaxation rates of Gd-BOPTA showed a strong dependency on HSA. In contrast, Gd-DTPA and Gd-BT-DO3A demonstrated little or no relevant dependency. On the basis of these results, the influence of serum protein concentration should be considered in both research studies and in clinical use.