Development of an Assay to Measure Lathanide Ion Concentrations in Biological Tissues

Abstract

Magnetic Resonance Imaging (MRI) enables clinicians to visualize soft tissues at high image resolution with good coverage of the entire body and low risk of side effects compared to methods that utilize ionizing radiation. MRI’s downfalls are its poor sensitivity and contrast. The use of lanthanide-based contrast agents provides a way to improve the image sensitivity and contrast by improving the MRI signal in certain organs and the signal difference between signal-enhanced and unenhanced organs. However, lanthanide-based contrast agents can stay in the body for long periods of time and can cause complications, especially in patients with poor kidney function (sometimes leading to Nephrogenic Systemic Fibrosis). Currently, pre-clinical studies of new MRI contrast agents require tissue samples to be analyzed via inductively coupled plasma mass spectrometry (ICP-MS) to determine the bio-distribution of the agent in the organs of the body. However, this method is both time-consuming and costly (~$50 per sample). We propose a method that utilizes nuclear magnetic resonance (NMR) spectroscopy as an analytical tool to measure lanthanide concentration. When lanthanide ions are present, a magnetic susceptibility causes a shift in the NMR frequencies emitted by the sample. This shift, called the bulk magnetic susceptibility (BMS) shift, is proportionally related to the concentration of lanthanide ions in the tissue sample. In this study, the BMS shifts of the lanthanides gadolinium (Gd) at concentrations of 0.10-5.00 mM and dysprosium (Dy) at concentrations of 0.50-10.00 mM were measured to confirm the viability of this quick, accurate, and inexpensive assay of lanthanide concentrations within biological tissues.