'Uniquely higher' relaxivity rates give gadobenate an edge

Not all gadolinium-based agents are created equal, and those agents with a higher relaxivity point offer a number of advantages in clinical MRI, according to a study in the American Journal of Neuroradiology. In this in vitro study, the investigators from the University of Pittsburgh in Pennsylvania demonstrated differences among various gadolinium-based contrast agents.

Gadobenate dimeglumine represents the first U.S. Food and Drug Administration (FDA)-approved gadolinium-based MR imaging contrast agent (GBMCA) with "noticeably higher R1 and R2 relaxivities and slightly different biodistribution and excretion pathways from those seen in the four older FDA-approved GBMCAs," wrote Dr. Andrew Bleicher and Dr. Emanuel Kanal (AJNR, January 9, 2008).

For this study, the following five FDA-approved GBCMAs were analyzed:

  • Gadobenate dimeglumine (MultiHance, Bracco Diagnostics, Princeton, NJ)
  • Gadoteridol (ProHance, Bracco)
  • Gadodiamide (Omniscan, GE Healthcare, Chalfont St. Giles, U.K.)
  • Gadoversetamide (OptiMark, Mallinckrodt, Hazelwood, MO)
  • Gadopentetate DTPA (Magnevist, Berlex, Montville, NJ)

Phantom imaging studies were done on a 1.5-tesla scanner and a 3-tesla scanner (Signa LX 0.1 and Signa LX VH7, GE Healthcare). Each of the five agents was diluted into a 5-mL concentration of a human serum substitute (Seronorm, Seros AS, Billingstad, Norway). For each agent, 10 tubes of this solution were imaged so that the total phantom consisted of 50 tubes. The MR sequence was five axial images in multisection mode for each sequence, with the middle sequence (image 3) used for analysis.

According to the results, when parameters were set for clinical, contrast-enhanced T1-weighted imaging, the highest signal intensities measured were for gadobenate, followed by gadopentetate, gadoteridol, gadoversetamide, and gadodiamide. Based on low-dilution factors standard for perfusion-weighted imaging, gadobenate showed the lowest signal intensities and the greatest T2* shortening effects. Also in perfusion-weighted imaging, the rate of signal intensity decrease, with increasing TE values, was greatest for gadobenate.

The authors also noted that there were higher signal intensities at 3-tesla MR versus 1.5-tesla, and those benefits were maintained with gadobenate.

"This study was performed to investigate the claim that gadobenate has uniquely higher R1 and R2 relaxivities.... Our data support the claim that ... gadobenate yielded greater signal intensities at physiologic concentrations on typical (T1-weighted imaging) sequences (i.e., short TE, short TR sequences) than did the other four GBMCAs," they wrote. "Gadobenate also demonstrated even greater differences in the T2 shortening effects ... at given dilution factors as might represent those used in clinical (perfusion-weighted) imaging."

Bleicher and Kanal outlined the clinical applications of their results. First, smaller doses of gadobenate could be used for perfusion-weighted imaging without sacrificing contrast-to-noise (CNR) ratio.

Also, more generally, "increase relaxivity can be converted into any of several clinical benefits," they noted. "These include greater signal intensity-to-noise ratios and, therefore, CNRs between enhancing tissues and nonenhancing background structure, thus increasing resolving power and lesion detectability," they explained, adding that this improvement could be beneficial for pinpointing tiny lesions and smaller vessels.

Finally, lower doses could bring about cost savings, as well as increased safety for patients in whom gadolinium administration might be questionable, such as those with renal disorders, they suggested.

"With a dose relationship now being established between the development of nephrogenic systemic fibrosis (NSF) in patients with renal failure and total administered GBMCA, administering lower doses seems to provide a direct patient benefit in this regard," they stated.

In terms of this dose relationship and NSF, the authors cited a November 2007 case-controlled study in which 19 subjects with chronic renal failure and 19 control subjects were all exposed to gadodiamide.

In the earlier study, the researchers from Herlev Hospital in Herlev and Gentofte Hospital in Hellerup, both in Denmark, determined that the subjects with chronic renal failure were given a mean gadodiamide dose of 0.29 mmol/kg, shortly before they showed the first signs of NSF. Meanwhile, the controls were exposed to a mean dose of 0.28 mmol/kg.

The Danish authors found that cumulative gadodiamide exposure while in chronic kidney disease stage 5 was significantly higher among cases compared with controls. In addition, cumulative gadodiamide exposure, along with other factors, increased the risk of gadodiamide-related NSF (Nephrology, Dialysis, Transplantation, November 2007, Vol. 22:11, pp. 3174-3178).

In an interesting aside, Bleicher and Kanal noted that they expected relaxivities to be essentially the same for the four older agents, but were surprised to see that there was a difference among the formulas and the degree of T1 shortening, even at the same dilution factors.

By Shalmali Pal
AuntMinnie.com staff writer
January 23, 2008

Related Reading

Studies outline techniques for ramping up MR in renal artery imaging, January 10, 2008

Gadolinium release linked to overall stability of contrast agent, may trigger NSF, January 9, 2008

AJR study: Women more likely to have gadolinium reactions, but acute cases remain mostly mild, December 21, 2007

Transglutaminases seen as 'missing link' in nephrogenic systemic fibrosis, October 18, 2007

MR experts take issue with FDA gadolinium warning, September 18, 2007

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