Abstract
The development and validation of MRI contrast agents consisting of a lanthanide chelate often requires a determination of the concentration of the agent in ex vivo tissue. We have developed a protocol that uses 70% nitric acid to completely digest tissue samples that contain Gd(III), Dy(III), Tm(III), Eu(III), or Yb(III) ions, or the MRI contrast agent gadodiamide. NMR spectroscopy of coaxial tubes containing a digested sample and a separate control solution of nitric acid was used to rapidly and easily measure the bulk magnetic susceptibility (BMS) shift caused by each lanthanide ion and gadodiamide. Each BMS shift was shown to be linearly correlated with the concentration of each lanthanide ion and gadodiamide in the 70% nitric acid solution and in digested rat kidney and liver tissues. These concentration measurements had outstanding precision, and also had good accuracy for concentrations ≥10 mM for Tm(III) Eu(III), and Yb(III), and ≥3 mM for Gd(III), gadodiamide, and Dy(III). Improved sample handling methods are needed to improve measurement accuracy for samples with lower concentrations.
Highlights
MRI contrast agents that consist of Gd(III) chelates are often used to enhance the image contrast of anatomical features during clinical diagnoses
The bulk magnetic susceptibility (BMS) shift measured for each tissue sample was converted to a concentration of lanthanide ion and gadodiamide using each calibration determined with lanthanide ion and gadodiamide solutions
The concentrations of each lanthanide ion and gadodiamide in nitric acid were linearly correlated with BMS shifts acquired at 7T magnetic field strength. (Figure 2a,b)
Summary
MRI contrast agents that consist of Gd(III) chelates are often used to enhance the image contrast of anatomical features during clinical diagnoses. Molecular imaging studies of animal models require the accurate measurement of tissue concentrations of MRI contrast agents to validate imaging results. A stock solution of each lanthanide ion or gadodiamide was added to a tissue sample, and diluted with distilled water, to create a range of tissue samples that ranged between 0.1–5.0 mM for GdCl3 and gadodiamide, 0.5–10 mM for DyCl3, and 1.0–50.0 mM for TmCl3, EuCl3, and YbCl3.
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