How the Chemical Properties of GBCAs Influence Their Safety Profiles In Vivo

The extracellular class of gadolinium-based contrast agents (GBCAs) is an essential tool for clinical diagnosis and disease management. In order to better understand the issues associated with GBCA administration and gadolinium retention and deposition in the human brain, the chemical properties of GBCAs such as relative thermodynamic and kinetic stabilities and their likelihood of forming gadolinium deposits in vivo will be reviewed. The chemical form of gadolinium causing the hyperintensity is an open question. On the basis of estimates of total gadolinium concentration present, it is highly unlikely that the intact chelate is causing the T1 hyperintensities observed in the human brain. Although it is possible that there is a water-soluble form of gadolinium that has high relaxitvity present, our experience indicates that the insoluble gadolinium-based agents/salts could have high relaxivities on the surface of the solid due to higher water access. This review assesses the safety of GBCAs from a chemical point of view based on their thermodynamic and kinetic properties, discusses how these properties influence in vivo behavior, and highlights some clinical implications regarding the development of future imaging agents.

Screening Breast MRI and Gadolinium Deposition: Cause for Concern?

Gadolinium-based contrast agents (GBCAs) have been used worldwide for over 30 years and have enabled lifesaving diagnoses. Contrast-enhanced breast MRI is frequently used as supplemental screening for women with an elevated lifetime risk of breast cancer. Data have emerged that indicate a fractional amount of administered gadolinium is retained in the bone, skin, solid organs, and brain tissues of patients with normal renal function, although there are currently no reliable data regarding the clinical or biological significance of this retention. Linear GBCAs are associated with a higher risk of gadolinium retention than macrocyclic agents. Over the course of their lives, screened women may receive high cumulative doses of GBCA. Therefore, as breast MRI screening utilization increases, thoughtful use of GBCA is indicated in this patient population.

Prospective multicenter assessment of patient preferences for properties of gadolinium-based contrast media and their potential socioeconomic impact in a screening breast MRI setting

Objective It is unknown how patients prioritize gadolinium-based contrast media (GBCM) benefits (detection sensitivity) and risks (reactions, gadolinium retention, cost). The purpose of this study is to measure preferences for properties of GBCM in women at intermediate or high risk of breast cancer undergoing annual screening MRI. Methods An institutional reviewed board-approved prospective discrete choice conjoint survey was administered to patients at intermediate or high risk for breast cancer undergoing screening MRI at 4 institutions (July 2018–March 2020). Participants were given 15 tasks and asked to choose which of two hypothetical GBCM they would prefer. GBCMs varied by the following attributes: sensitivity for cancer detection (80–95%), intracranial gadolinium retention (1–100 molecules per 100 million administered), severe allergic-like reaction rate (1–19 per 100,000 administrations), mild allergic-like reaction rate (10–1000 per 100,000 administrations), out-of-pocket cost ($25–$100). Attribute levels were based on published values of existing GBCMs. Hierarchical Bayesian analysis was used to derive attribute “importance.” Preference shares were determined by simulation. Results Response (87% [247/284]) and completion (96% [236/247]) rates were excellent. Sensitivity (importance = 44.3%, 95% confidence interval = 42.0–46.7%) was valued more than GBCM-related risks (mild allergic-like reaction risk (19.5%, 17.9–21.1%), severe allergic-like reaction risk (17.0%, 15.8–18.1%), intracranial gadolinium retention (11.6%, 10.5–12.7%), out-of-pocket expense (7.5%, 6.8–8.3%)). Lower income participants placed more importance on cost and less on sensitivity (p < 0.01). A simulator is provided that models GBCM preference shares by GBCM attributes and competition. Conclusions Patients at intermediate or high risk for breast cancer undergoing MRI screening prioritize cancer detection over GBCM-related risks, and prioritize reaction risks over gadolinium retention. Key Points • Among women undergoing annual breast MRI screening, cancer detection sensitivity (attribute “importance,” 44.3%) was valued more than GBCM-related risks (mild allergic reaction risk 19.5%, severe allergic reaction risk 17.0%, intracranial gadolinium retention 11.6%, out-of-pocket expense 7.5%). • Prospective four-center patient preference data have been incorporated into a GBCM choice simulator that allows users to input GBCM properties and calculate patient preference shares for competitor GBCMs. • Lower-income women placed more importance on out-of-pocket cost and less importance on cancer detection (p < 0.01) when prioritizing GBCM properties.