EVALUATION OF THE BIO-DISTRIBUTION OF LANTHANIDE IONS IN MOUSE TISSUE USING NMR SPECTROSCOPY

picture of Sandra Gonzalez presenting his/her poster: EVALUATION OF THE BIO-DISTRIBUTION OF LANTHANIDE IONS IN MOUSE TISSUE USING NMR SPECTROSCOPY

Sandra Gonzalez , Dina V. Hingorani, and Mark D. Pagel PhD

EVALUATION OF THE BIO-DISTRIBUTION OF LANTHANIDE IONS IN MOUSE TISSUE USING NMR SPECTROSCOPY

The attractiveness of magnetic resonance imaging (MRI) as an imaging modality results from visualizing soft tissues at high image resolution, good coverage of the entire body and low side effects due to the lack of ionizing radiation. However the use of MRI involves overcoming poor sensitivity and poor contrast. The development of contrast agents improves the MRI signal in some organs and the signal difference between signal-enhanced and unenhanced organs improves image contrast. Nonetheless, these lanthanide based contrast agents can stay in the body for long periods of time, especially in patients with poor kidney function, sometimes leading to Nephrogenic Systemic Fibrosis. Preclinical studies of new MRI contrast agents require tissue samples to be analyzed to validate MRI results, typically using inductively coupled plasma mass spectrometry (ICP MS) to determine the bio-distribution of the agent in different organs. However, this method of analysis requires several days and the cost per sample is usually quite high (~$50/sample).

We propose nuclear magnetic resonance spectroscopy (NMR) as an alternative analytical tool to detect contrast agents in tissue samples. Lanthanide ions create a unique magnetic susceptibility that causes a shift in the NMR frequencies that are emitted by the sample. This shift, or “delta value,” is proportionately related to the concentration of lanthanide ions in a chemical sample. However, the best method for preparing a tissue sample for this type of NMR analyses is not known.  In our study, we compared several methods for preparation of mouse kidney and liver tissues samples for NMR analyses. These methods compared the recovery of lanthanide ions from kidney and liver tissues with water and nitric acid, using combinations of heating, sonication, and filtration.  We found that our most precise method used nitric acid and sonication, which resulted in 93±7% recovery of thulium lanthanide ions. This level of recovery is sufficient for evaluating the bio-distribution of MRI contrast agents, and provides a rapid and low-cost alternative to ICP-MS analyses.

(This research was sponsored by NIH T34 GM008718, NIBIB/NIH 1R01CA167183-01 and 1R01CA169774-01 and through the University of Arizona Cancer Center and the NCI/NIH through grant number P50CA95060.)

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