Gadolinium (Gd) based contrast agents (GBCA) are widely used in magnetic resonance imaging (MRI) and are paramount to cancer diagnostics. In this context, accurate quantification of Gd in blood and/or plasma (biological media) is essential to tumor pharmacokinetic analysis, and current methods for doing so are both low throughput and clinically unavailable. Here, we have demonstrated the use of a sensitized GBCA, Gd[DTPA-cs124], to measure the concentration of Gd in biological media via luminescence quantification following transmetallation with a terbium (Tb) salt. As such, our assay provides a straightforward and high throughput method of measuring Gd in biological media using a standard laboratory plate reader. Furthermore, we report both increased stability and relaxivity for Gd[DTPA-cs124], as well as its efficacy as an MRI contrast agent when compared to its clinically approved analog, Magnevist. Our results indicate that similar chemical modification to existing clinically approved GBCA may likewise yield favorable property changes, with the added ability to quantify Gd.

Depiction of our Gd quantification assay workflow. Gd[DTPA-cs124] is administered to C57BL6 mice as a bolus injection at a concentration of 0.1 mmol/kg via tail vein catheterization, followed by MRI. Immediately after imaging, a 10 μL blood sample is drawn and treated with a buffered Tb standard, causing transmetallation and allowing for measurement of Gd via luminescence quantification.

Standard curves for quantifying Gd in aqueous media, 5% human plasma, and 5% human blood, using the assay herein described. The limits of detection are characterized as follows: 0.46 nM for aqueous media, 0.43 nM for 5% human plasma, and 3.02 nM for 5% human blood.

James Tranos

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