MRI Contrasting Agents: Broader Applications

Posted on December 03, 2020

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Why Are the Contrast Agents Used in MRI Important?

Magnetic resonance imaging (MRI) is one of the top ten most common medical diagnostic tests conducted around the world with tens of millions of contrast enhanced MRI exams performed annually. Contrasting agents are used for MRI exams to enhance diagnostic accuracy and information that often cannot be obtained from other noninvasive techniques. The primary MRI contrast agents used today are gadolinium(III) (GBCA) based. This class of inorganic drug is among the most successful of all inorganic drugs along with platinum anticancer compounds and technetium-99m radiopharmaceuticals used for bone imaging. GBCAs are widely used not only due to their diagnostic enhancement ability, but also because they are remarkably safe compared to other imaging agents. GBCAs are used in approximately 40% of all MRI exams and about 60% of all neuro MRI exams.1 This wide usage leads to about 50 metric tons of gadolinium being administered annually.2

Avanti’s Gadolinium Based MRI Contrasting Agents are Being put to Good Use!

Liposomes, specifically phospholipid-based vesicles, have been studied as potential nanocarriers of MRI contrast agents including GBCAs. These studies have lead to the understanding that liposomes can serve as diagnostic and theranostic agents for imaging and treating various pathologies such as cancers of different organs. These liposomes represent a new and important possibility for targeted diagnostic systems. These higher molecular weight, biocompatible nanocarriers often differ with regards to biodistribution from their low molecular weight Gd complex counterparts. This difference in biodistribution could lead to a broad range of applications. Recently, liposomes composed of a gadolinium (Gd)-chelating lipid have been studied due to the ease of capturing targeted moieties on their surface using techniques such as copper-free click-chemistry.

Specifically, Avanti’s 18:0 PE-DTPA (Gd) product was used to prepare liposomes with a near infrared dye to test nano-safety of these liposomes in MRI exams. The liposomes were composed of PE-DTPA (Gd), DSPC, and cholesterol, and were tested in vitro for toxological effects. Several biomarkers of toxicity were measured including cytotoxicity, sphingolipid metabolism, induction of early response genes and markers of heat shock response, endoplasmic reticulum stress, oxidative stress, DNA damage response, inflammation and modulation of xenobiotic metabolizing enzymes. The study showed that the Gd-liposomes had no adverse impact on human derived hepatocyte-like HepaRG cells and macrophages. The study was done in vitro and still needs to be studied in vivo, but the results indicate that Gd-liposomes will leave the human immune system silent.3

  1. Runge VM Critical Questions Regarding Gadolinium Deposition in the Brain and Body after Injections of the Gadolinium-Based Contrast Agents, Safety, and Clinical Recommendations in Consideration of the EMA’s Pharmacovigilance and Risk Assessment Committee Recommendation for Suspension of the Marketing Authorizations for 4 Linear Agents. Invest. Radiol 2017, 52, 317–323.
  2. Wahsner J, Gale EM, Rodríguez-Rodríguez A, Caravan P. Chemistry of MRI Contrast Agents: Current Challenges and New Frontiers. Chem Rev. 2019;119(2):957-1057. doi:10.1021/acs.chemrev.8b00363

3. Simeckova P, Hubatka F, Kotoucek J, et al. Gadolinium labelled nanoliposomes as the platform for MRI theranostics: in vitro safety study in liver cells and macrophages. Sci. Rep. 2020;10:4780.