Gadolinium-induced fibrosis testing by protein targeting assay and superparamagnetic iron oxide nanoparticle-based magnetic resonance microscopy of skin and kidneys

Abstract

Abstract Gadolinium-based magnetic resonance imaging (MRI) contrast agents cause undefined fibrosis in kidneys and skin damage. Magnetic resonance microimaging of rat skin and kidney was used first time to identify the physical factors modulating the gadolinium Omniscan®-induced fibrosis by protein targeting. A 500-MHz MR imaging was done to visualize fibrosis in gadolinium-treated animals. Cationic superparamagnetic iron oxide magnetoferritin (SPIOM) was injected in rat to target basement membrane (in rat kidney and different skin structures including epidermis glycolipids and dermis proteins. After MR imaging, excised rat skin and kidneys tissues were imaged by ex vivo 900 MHz MR microimaging to confirm renal fibrosis and skin epidermis thickening. The proton density-weighted images visualized micro details of skin structures and nephron territories while T2-weighted images showed better contrast of tissue structures in both skin and kidney. The gadolinium further enhanced the image contrast and targeted the proteins in renal basement membrane and viable proteins in epidermis. SPIOM enhanced the tissue contrast due to dephasing effect caused by SPIOM on structural changes in nephron and epidermis. Conclusion: Tissue membrane protein and chelate ligand group binding with gadolinium biophysical interaction at molecular level may develop fibrosis. SPIOM injection improved the dephased image contrast of different structures in both skin and nephrons. The epidermis thickening and nephrofibrosis changes may be associated with nephrogenic systemic fibrosis or fibrosing dermatopathy.