Characterization of a gadolinium-tagged modular contrast agent by element and molecular mass spectrometry
- 17 March 2004
- journal article
- research article
- Published by Royal Society of Chemistry (RSC) in Journal of Analytical Atomic Spectrometry
- Vol. 19 (7) , 852-857
- https://doi.org/10.1039/b315649d
Abstract
A modular gadolinium-tagged contrast agent for magnetic resonance imaging has been characterized by mass spectrometry. The synthetic construct exhibits a molecular weight of about 8 kDa and is composed of three modules, (i) a diethylene triamine pentaacetic acid (DTPA) module for complexation of Gd3+, (ii) a peptide nucleic acid (PNA) sequence for hybridisation with a complementary nucleic acid sequence, and (iii) a peptide transmembrane transport module. Electrospray mass spectrometry (nanoESI-MS) was used for determination of the molecular weight of the intact functional peptide and of a synthetic intermediate. In general, signals were observed for both the Gd-complexed and uncomplexed forms. For measurement of the Gd saturation size-exclusion chromatography (SEC) was coupled on-line to high-resolution inductively coupled plasma mass spectrometry (ICP-MS) and 32S, 34S and 157Gd were simultaneously monitored. The monitoring of sulfur as a marker element for the organic part of the molecule is possible due to the presence of a disulfide bridge and a methionine residue. The molar Gd/S ratio provides a measure of the Gd saturation, which was found to be in the range of 55% to 85% in the samples investigated. Moreover, a small amount of iron tightly complexed to the contrast agent constructs was detected and was probably taken up during synthesis or purification. Thus, the combined application of SEC-ICP-MS and nanoESI-MS delivers the complementary element and molecular information required for a reliable characterization of metal-tagged contrast agents of complex, modular design.Keywords
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