Sensing Lanthanide Metal Content in Biological Tissues with Magnetic Resonance Spectroscopy

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.

Lanthanide complexes with polyaminopolycarboxylates as prospective NMR/MRI diagnostic probes: peculiarities of molecular structure, dynamics and paramagnetic properties

“…In the general case, when analyzing Eq. ( 7), one can simultaneously use 1 H, 13 C, 19 F, 31 P etc. NMR data and data for different Ln ions, which depends on the system under study.…”

“…The complexes of Ln with PAPC ligands exhibit common properties: good solubility in aqueous media, thermodynamic and kinetic stability, low toxicity and relatively fast excretion half-time. In particular, lanthanides with such PAPC ligands as DOTA, DTPA and EDTA have been reported [12][13][14] for using Gd complexes with DOTA and DTPA as contrasting relaxation reagents [15][16][17][18][19][20][21]. As shift agents for NMR applications, -diketonate complexes with paramagnetic [22][23][24] the case of organic media and [Ln(H 2 O) n (EDTA)] [25,26] the case of aqueous media have been used [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45].…”

Magnetic Resonance Sensors

“…The difficulty with their use is that ex vivo tissue concentrations are often required. In [ 9 ] the authors present a method which uses changes in magnetic susceptibility to determine the concentration of a range of Lanthanide chelates, using NMR spectroscopy. Although presented using a high field spectrometer, this could easily be performed in the clinical setting using a bench top spectrometer system such as the Magritek Spinsolve [ 10 ] improving the efficiency at point of care.…”