Data on mesoporous silica modified with 1,2-hydroxypyridinone (1,2-HOPO) for capturing gadolinium based contrast agents in vitro and in a chronic kidney disease rodent model have been recently published in Scientific Reports. The work was done in collaboration between PDX Pharmaceuticals, the Biomedical Engineering Department of Oregon Health and Science University, and the Pacific Northwest National Laboratory (PNNL). Funding was provided by the National Institute of General Medical Sciences (NIGMS), the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the Oregon Nanoscience and Microtechnologies Institute (ONAMI), and OHSU’s Office of Vice President for Research (VPR) fund.
Gadolinium based contrast agents (GBCAs) have been linked to toxicity in patients, regardless of having impaired or normal renal function. Currently, no therapy is considered highly effective for removing gadolinium (Gd) from the body. We propose a new strategy to reduce blood Gd content that facilitates whole body removal of Gd using a hemoperfusion system consisting of a cartridge of porous silica beads (Davisil®) functionalized with 1,2-HOPO. Herein, we report optimization of the hemoperfusion system using an ex vivo blood and an in vivo rat model of chronic kidney disease (CKD). In our ex vivo system, 1,2-HOPO-Davisil outperformed Gambro activated charcoal (AC), which is commonly used in clinical hemoperfusion of aqueous toxins, in terms of Gd capture capacity and rate. In the CKD rat model, the 1,2-HOPO-Davisil hemoperfusion system removed Gd by 3.4 times over the Gambro AC system. 1,2-HOPO-Davisil did not change complete blood counts and common blood biochemistry. Thus, this strategy has great potential for clinical translation to manage GBCAs after magnetic resonance imaging (MRI), before Gd can deposit in the body and cause long-term toxicity. Although gadodiamide was used as a proof of concept model for GBCAs in this study, 1,2-HOPO functionalized mesoporous silica could also capture dissociated Gd and other GBCAs.