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 310 mM for Tm(III) Eu(III), and Yb(III), and 33 mM for Gd(III), gadodiamide, and Dy(III). Improved sample handling methods are needed to improve measurement accuracy for samples with lower concentrations.
References
[1]
Runge, V.M.; Muroff, L.R.; Wells, J.W. Principles of contrast enhancement in the evaluation of brain diseases: An overview. J. Mag. Reson. Imag. 2005, 7, 5–13.
[2]
Moriarty, J.M.; Finn, J.P.; Fonesca, C.G. Contrast agents used in cardiovascular magnetic resonance imaging: Current issues and future directions. Am. J. Cardiovasc. Drugs 2010, 10, 227–237.
[3]
Zhou, Z.; Lu, Z.R. Gadolinium-based contrast agents for magnetic resonance cancer imaging. Nanomed. Nanobiotechnol. 2013, 5, 1–18.
[4]
Stafford Johnson, D.B.; Prince, M.R.; Chenevert, T.L. Magnetic resonance angiography: A review. Acad. Radiol. 1998, 5, 289–305.
[5]
O'Connor, J.P.B.; Jackson, A.; Parker, G.J.M.; Jayson, G.C. DCE-MRI biomarkers in the clinical evaluation of antiangiogenic and vascular disrupting agents. Brit. J. Cancer 2007, 96, 189–195.
[6]
Dijkhuizen, R.M. Advances in MRI-Based detection of cerebrovascular changes after experimental traumatic brain injury. Translat. Stroke Res. 2011, 2, 524–532.
Gore, J.C.; Manning, H.C.; Quarles, C.C.; Waddell, K.W.; Yankeelov, T.E. Magnetic resonance in the era of molecular imaging of cancer. Mag. Reson. Imag. 2011, 29, 587–600.
[9]
Yoo, B.; Pagel, M.D. An overview of responsive MRI contrast agents for molecular imaging. Front. Biosci. 2008, 13, 1733–1752.
[10]
Sheth, V.R.; Pagel, M.D. CEST & PARACEST MRI Contrast Agents for Imaging Cancer Biomarkers. In Molecular Imaging Probes for Cancer Research; Chen, X., Ed.; World Scientific Publishing: Hackensack, NJ, USA, 2012; pp. 689–713.
Buckley, D.L.; Parker, G.J.M. Measuring Contrast Agent Concentration in T1-Weighted Dynamic Contrast-Enhanced MRI. In Medical Radiology—Diagnostic Imaging and Radiation Oncology; Jackson, A., Buckley, D., Parker, G.J.M., Eds.; Springer: New York, NY, USA, 2005; pp. 69–79.
[13]
Ali, M.M.; Liu, G.; Shah, T.; Flask, C.A.; Pagel, M.D. Using two chemical exchange saturation transfer magnetic resonance imaging contrast agents for molecular imaging studies. Acc. Chem. Res. 2009, 42, 915–924.
[14]
Crayton, S.H.; Elias, D.R.; Al Zaki, A.; Cheng, Z.; Tsourkas, A. ICP-MS analysis of lanthanide-doped nanoparticles as a non-radiative, multiplex approach to quantify biodistribution and blood clearance. Biomat 2012, 33, 1509–1519.
[15]
Barge, A.; Cravotto, G.; Gianolio, E.; Fedeli, F. How to determine free Gd and free ligand in solution of Gd chelates. A technical note. Contrast Media Mol. Imag. 2006, 1, 184–188.
[16]
Brown, R.; Clarke, D.W.; Daffner, R.H. Is a mixture of gadolinium and iodinated contrast material safe during MR arthrography? Am. J. Roentgenol. 2000, 175, 1087–1090.
[17]
Rohwer, H.; Collier, N.; Hosten, E. Spectrophotometric study of arsenazo III and its interactions with lanthanides. Anal. Chim. Acta. 1995, 314, 219–223.
[18]
Evans, D.F. The determination of the paramagnetic susceptibility of substances in solution by nuclear magnetic resonance. J. Chem. Soc. 1959, doi:10.1039/JR9590002003.
Corsi, D.M.; Platas-Iglesias, C.; von Bekkum, H.; Peters, J.A. Determination of paramagnetic lanthanide(III) concentrations from bulk magnetic susceptibility shifts in NMR spectra. Mag. Reson. Chem. 2001, 39, 723–726.
[21]
Gysling, H.; Tsutsui, M. Organolanthanides and Organoactinides. Adv. Organomet. Chem. 1971, 9, 361–395.
[22]
Gerothanassis, I.P.; Lauterwein, J. Oxygen-17 NMR spectroscopy: Referencing in diamagnetic and paramagnetic solutions. Mag. Reson. Chem. 1986, 24, 1034–1038.
[23]
Fossheim, S.; Johansson, C.; Fahlvik, A.K.; Grace, D.; Klaveness, J. Lanthanide-based susceptibility contrast agents: Assessment of the magnetic properties. Mag. Reson. Med. 1996, 35, 201–206.
[24]
Parker, M.M.; Humoller, F.L.; Mahler, D.J. Determination of copper and zinc in biological material. Clin. Chem. 1967, 13, 40–48.
[25]
Schulten, H.R.; Ziskoven, R. Determination of thallium in brain tissue of the mouse by stable isotope dilution and field desorption mass spectrometry. J. Physiol. 1978, 284, 170P–171P.
[26]
Dos Santos, W.P.C.; Hatje, V.; da Santil, D.; Fernandes, A.P.; Korn, M.G.A.; de Souza, M.M. Optimization of a centrifugation and ultrasound-assisted procedure for the determination of trace and major elements in marine invertebrates by ICP OES. Microchemical. J. 2010, 95, 169–173.
[27]
O'Brien, R.D. Nitric acid digestion of tissues for liquid scintillation counting. Anal. Biochem. 1964, 7, 251–254.
[28]
Josan, J.S.; de Silva, C.R.; Yoo, B.; Lynch, R.M.; Pagel, M.D.; Vagner, J.; Hruby, V.J. Fluorescent and lanthanide labeling for ligand screens, assays, and imaging. Meth. Mol. Biol. 2011, 716, 89–126.
[29]
Andres, Y.; Thouand, G.; Boulalam, M.; Mergeay, M. Factors influencing the biosorption of gadolinium by microorganisms and its mobilisation from sand. Appl. Microbiol. Biotech. 2000, 54, 262–267.
[30]
Anan, Y.; Awaya, Y.; Ogihara, Y.; Yosida, M.; Yawata, A.; Ogra, Y. Comparison in accumulation of lanthanide elements among three brassicaceae plant sprouts. Bull. Environ. Contam. Toxicol. 2012, 89, 133–137.
[31]
Parsons, J.G.; Peralta-Videa, J.R.; Tiemann, K.J.; Saupe, G.B.; Gardea-Torresdey, J.L. Use of chemical modification and spectroscopic techniques to determine the binding and coordination of gadolinium(III) and neodymium(III) ions by alfalfa biomass. Talanta 2005, 67, 34–45.
[32]
Vodyanitskii, Y.N.; Savichev, A.T. Lanthanides in Soils: X-ray Determination, Spread in Background and Contaminated Soils in Russia. In Geochemistry: Earth's System Processes; InTech: New York, NY, USA, 2012; pp. 389–412.
[33]
Shumilin, E.; Rodriguez-Figueroa, G.; Sapozhnikov, D. Lanthanide contamination and lanthanide concentration and strong positive Europium Anomalies in the Surface Sediments of the Santa Rosalia Copper Mining Region, Baja California Peninsula, Mexico. Bull. Environ. Contamin. Toxicol. 2005, 75, 308–315.
[34]
Neal, C. Rare earth element concentrations in dissolved and acid available particulate forms for eastern UK rivers. Hydrol. Earth Syst. Sci. 2007, 11, 313–327.
[35]
Protano, G.; Riccobono, F. High contents of rare earth elements (REEs) in stream waters of a Cu-Pb-Zn mining area. Environ. Pollut. 2002, 117, 499–514.
[36]
Naumov, A.V. Review of the world market of rare-earth metals. Russ. J. Non-Ferrous Metals 2008, 49, 14–22.
