Gadolinium (Gd) based contrast agents (GBCAs) are widely
used in
magnetic resonance imaging (MRI) and are paramount to cancer diagnostics
and tumor pharmacokinetic analysis. Accurate quantification of gadolinium
concentration is essential to monitoring the biodistribution, clearance,
and pharmacodynamics of GBCAs. However, current methods of quantifying
gadolinium in blood or plasma (biological media) are both low throughput
and clinically unavailable. Here, we have demonstrated the use of
a sensitized gadolinium chelate, Gd[DTPA-cs124], as an MRI contrast
agent that can be used to measure the concentration of gadolinium
via luminescence quantification in biological media following transmetalation
with a terbium salt. Gd[DTPA-cs124] was synthesized by conjugating
carbostyril-124 (cs124) to diethylenetriaminepentaacetic acid (DTPA)
and chelating to gadolinium. We report increases in both stability
and relaxivity compared to the clinically approved analog Gd[DTPA]
(gadopentetic acid or Magnevist). In vivo MRI experiments were conducted
using C57BL6 mice in order to further illustrate the performance of
Gd[DTPA-cs124] as an MRI contrast agent in comparison to Magnevist.
Our results indicate that similar chemical modification to existing
clinically approved GBCA may likewise provide favorable property changes,
with the ability to be used in a gadolinium quantification assay.
Furthermore, our assay provides a straightforward and high-throughput
method of measuring gadolinium in biological media using a standard
laboratory plate reader.