The Detection and Characterization of Nanoparticulate Heavy Metals in Epithelial Tissues in Patients with Nephrogenic Fi
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1063-OO10-06
The Detection and Characterization of Nanoparticulate Heavy Metals in Epithelial Tissues in Patients with Nephrogenic Fibrosing Dermopathy Reed Ayers1, Whitney High2, John Chandler1, and Jim Ranville3 1 Metallurgical and Materials engineering, Colorado School of Mines, 1500 Illinois St., Golden, CO, 80401 2 Dermatology, University of Colorado Health Sciences Center, P.O. Box 6510, Mail Stop F703, Aurora, CO, 80045-0510 3 Chemistry and Geochemistry, Colorado School of Mines, 1500 Illinois St., Golden, CO, 80401 ABSTRACT Background: Nephrogenic fibrosing dermopathy (NFD) is a disease of unknown etiology that affects a subset of patients with renal insufficiency. Recent publications suggested an association between exposure to gadolinium-containing contrast agents and subsequent development of NFD. We sought to detect gadolinium within the skin and soft tissue of patients with NFD who were exposed to gadolinium-based contrast. Methods: Paraffin embedded skin and soft tissue from NFD patients exposed to gadolinium, and from negative controls, was provided by the NFD Registry (New Haven, CT). The tissue was searched for metals using a field emission scanning electron microscope (FE-SEM) that was equipped with energy dispersion spectroscopy (EDS). Presence of gadolinium and other metals was verified through identification of unique and requisite X-ray emission spectra. Confirmation of gadolinium within tissue was provided using inductively coupled plasma mass spectrometry (ICP-MS). Results: Gadolinium was imaged and quantified in 4 of 14 tissue specimens from 7 patients with documented NFD who were exposed to gadolinium-based contrast. No gadolinium was imaged or detected in any of the 6 paraffin embedded specimens from 3 negative controls. Heart and skin have the largest concentrations (344. 2 µg/g and 335.2 µg/g respectively). In three of four gadolinium-containing specimens, the metal was confined to areas of fibrosis. In a single case,
gadolinium particles were detected in the papillary dermis underlying an actinic keratosis. In all cases the gadolinium particles appeared to be associated with cell bodies and were judged to be intracellular, possibly within lysosomes. Conclusion: In this pilot investigation, FE-SEM with EDS can be used to image and provide initial characterization of the agglomerations of metal nanoparticulates. Specific concentrations of Gd in the tissues are quantified using ICP-MS. In so doing, this work begins to define the spatial locations of specific concentrations of metals within tissues of patients with NFD. INTRODUCTION Gadolinium containing complexes are effective MRI contrast agents for diagnostic imaging. These complexes rely on the resident time of water in a Gd+3 containing ligand such diethylenetriaminepentaacetic acid (DTPA) or 1,4,7,10, tetraazacy clododecane-N,Nt,Ntt,Nttttetraacteic acid (DOTA). The resulting dipole-dipole interactions between water molecules bound to the ligand and metallic center result in a relaxation rate detected by the MRI.1 At the same time,
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