MultiHance (gadobenate dimeglumine) injection, 529 mg/mL is the first extracellular fluid (ECF) contrast agent (CA) to possess a weak and transient interaction with plasma proteins, a characteristic that endows MultiHance with up to twice the in vivo relaxivity of all other ECF contrast agents. (de Haen, 1999) This increased relaxivity could potentially contribute to improved lesion visualization.

The MultiHance molecule, gadobenate, has a structure very similar to that of gadopentetate, except that MultiHance has a benzyloxymethyl group protruding from the molecule (Figure 1). (de Haen, 1999) This lipophilic structure provides MultiHance with the ability to weakly and reversibly interact with plasma proteins and also to be taken up by functioning hepatocytes.

Relaxivity refers to the ability of an MR contrast agent to shorten proton relaxation times, thereby increasing signal intensity on T1-weighted MR-images. Initially during an MR-scan, energy in the form of a radiofrequency (RF) pulse (RF-excitation), is transferred to protons (mostly hydrogen nuclei). The MR-signal that is ultimately used to create an image is generated when protons following such an excitation lose energy and recover to steady state. Since the rate at which this process takes place (the relaxation rate) varies among tissues and body compartments, various organs and tissues appear different in the MR image. This difference (the image contrast) can be affected using contrast agents, making the difference between tissues more apparent (ie, contrast between normal tissue and lesions). The higher the relaxivity of a contrast agent, the easier it will be to see this difference.

Several characteristics of a contrast agent can impact the relaxivity; among these is the size of the molecule. A large molecule will tumble slower in plasma than a small one, thereby increasing the relaxation rate of nearby protons. MultiHance has the ability to transiently interact with serum proteins and effectively, during transit time in the body, behaves as a larger molecule than other gadolinium contrast agents, resulting in significantly higher relaxivity of MultiHance compared with other MR contrast agents currently on the market (Figure 1).

Figure 1. MultiHance in vivo relaxivity @ 0.5T. (de Haen, 1999)

The higher relaxivity of MultiHance, and thus higher capability to improve the contrast in MR-images, could potentially contribute to improved lesion visualization. Enhanced sensitivity may allow for better lesion visualization and lesion border delineation, as well as providing visualization of smaller, metastatic lesions (Figure 2). (Essig, 2003)

Figure 2. Increase in lesion Signal Intensity over time afterethe administration of 0.1 mmol/kg
of either MultiHance or gadopentetate dimeglumine at 1.5T

The gadobenate ion is eliminated predominately via the kidneys, with 78% to 96% of an administered dose recovered in the urine. A small percentage of the administered dose (0.6% to 4%) is taken up by functioning hepatocytes in the liver and eliminated via the biliary route and recovered in feces.

Over 3.5 million doses of MultiHance have been administered to patients worldwide since 1998. MultiHance has been shown to have a stability profile equal to or better than that of commonly used agents such as gadopentetate dimeglumine. (de Haen, 1999).

MultiHance is well tolerated, with a safety profile similar to other gadolinium MR contrast agents. The majority of adverse events are transient, self-resolving, and mild in intensity. (Kirchin 1998)

In clinical trials, MultiHance has been tested in 2,982 adult subjects. Adverse events were reported in <0.5% of adult subjects who received MultiHance. The most commonly reported adverse events were headache, nausea, dizziness and taste perversion. (MultiHance full PI)

MultiHance is available in 5-, 10-, 15-, and 20-mL single-dose vials, and 50- and 100-mL Multipack™* (Pharmacy Bulk Packages).

*Not for direct infusion.