Rapid In Vitro Quantification of a Sensitized Gadolinium Chelate via Photoinduced Triplet Harvesting.
Academic Article
Overview
abstract
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.
