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Will Improved Vascular Mapping Achieved with Gadobenate Dimeglumine Aid in Interpretation of Breast MR Images?

¹ Department of Radiology, Yale University School of Medicine, 333 Cedar St, PO Box 208042, New Haven, CT 06520-8042 Liane.Philpotts@yale.edu

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Use of gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany), the contrast agent most commonly used for breast magnetic resonance (MR) imaging, yields information about the kinetic characteristics (uptake and washout) of breast lesions. As with all gadolinium-based contrast agents, gadopentetate dimeglumine has a two-compartment biodistribution, with rapid diffusion from the vascular to the extracellular space. Another gadolinium-based contrast agent, gadobenate dimeglumine (MultiHance; Bracco Imaging, Milan, Italy), has similar two-compartment characteristics, but it also has transient protein binding such that its T1 relaxivity is approximately two times that of gadopentetate dimeglumine. Gadobenate dimeglumine has been tested in extensive trials in Europe and has recently received Food and Drug Administration approval in the United States.

In this issue of Radiology, Sardanelli et al (1) report the findings and data obtained in a European multicenter phase II trial that was performed by using three different doses of gadobenate dimeglumine—0.05, 0.10, and 0.20 mmol per kilogram of body weight—and a standard 0.10 mmol/kg dose of gadopentetate dimeglumine. They assessed the vascular mapping of the breast achieved with these two contrast agents and the relationship between ipsilateral increased vascularity and breast cancer.

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Vascularity can increase not only within a breast cancer lesion but also in the ipsilateral breast as a whole. Sardanelli et al (1) obtained vascular maps by using the maximum intensity projections from subtracted MR images. These images were read by readers who were blinded to the final histopathologic diagnosis of the lesion. To simulate normal clinical interpretation conditions, however, the lesions were not masked. The readers rated the depicted vascularity of each breast on a scale of 0–3. Compared with the vascular maps obtained with gadopentetate dimeglumine enhancement, markedly improved vascular maps were obtained with use of all doses of gadobenate dimeglumine and enabled assessment of increased ipsilateral vascularity. This finding of increased ipsilateral vascularity correlated significantly with malignancy: Sensitivity, specificity, accuracy, positive predictive, and negative predictive values were 88% (44 of 50 patients), 82% (14 of 17 patients), 87% (58 of 67 patients), 94% (44 of 47 patients), and 70% (14 of 20 patients), respectively, suggesting that observed differences in overall breast vascularity could be used as a sign of malignancy.

The assessment of vascularity, however, is somewhat subjective. The investigators strived for objectivity by using specific criteria such as the size (width and length) and number of vessels observed. Given that the lesions were not masked during readings, there was the potential for bias in the interpretations. Nonetheless, the findings were intuitive. Neoangiogenesis is known to occur in malignancies, and contrast agents that yield vascular maps may yield visible differences that are clinically important.

The Practice

Clinical use.—Gadobenate dimeglumine has been shown to have a safety profile similar to that of gadopentetate dimeglumine; only nonserious adverse reactions have been encountered (2). Thus, safety considerations should not hamper the adoption of this agent into clinical use.

While MR imaging is very sensitive for the detection of invasive cancer, its specificity is more variable. The sensitivity of MR imaging for the detection of intraductal carcinoma is generally lower than that for the detection of invasive disease. Clinically valuable advancements in breast MR imaging will be based on improvements in intraductal carcinoma detection (ie, sensitivity) and overall specificity (ie, differentiation of benign lesions with enough certainty to avoid biopsy).

Future opportunities and challenges.—While the results reported in the Sardanelli et al article (1) are interesting, it is uncertain whether the findings will influence breast MR imaging. Clinical utility will depend on whether the combination of breast vascular mapping and the traditional criteria used to determine the likelihood of malignancy (morphologic and kinetic features) will improve the interpretation of breast MR images. Further studies will be necessary to determine this, along with whether the finding of increased vascularity is observed with intraductal tumors also.

Summary

The findings of Sardanelli et al (1) show not only that gadobenate dimeglumine can be used to obtain vascular maps that are superior to those obtained with gadopentetate dimeglumine but also that a difference in vascularity between the two breasts is an indirect sign of malignancy. Further examinations will be necessary to assess whether the finding of ipsilateral vascularity, when combined with other interpretation criteria, improves overall diagnostic accuracy.

FOOTNOTES

See also the article by Sardanelli et al in this issue.

REFERENCES

1. Sardanelli F, Iozzelli A, Fausto A, Carriero A, Kirchin M. Gadobenate dimeglumine–enhanced MR imaging breast vascular maps: association between invasive cancer and ipsilateral increased vascularity. Radiology 2005; 235:791-797.[Abstract/Free Full Text]
2. Kirchin MA, Pirovano G, Venetianer C, Spinazzi A. Safety assessment of gadobenate dimeglumine (MultiHance): extended clinical experience from phase I studies to post-marketing surveillance. J Magn Reson Imaging 2001; 14:281-294.[CrossRef][Medline]

This article has been cited by other articles:

				F. Sardanelli Vascular Maps on Contrast-enhanced Breast MR Images: A New Approach Requiring Further Investigation Radiology, April 1, 2008; 247(1): 295 - 296. [Full Text] [PDF]

				F. Pediconi, C. Catalano, A. Roselli, S. Padula, F. Altomari, E. Moriconi, A. M. Pronio, M. A. Kirchin, and R. Passariello Contrast-enhanced MR Mammography for Evaluation of the Contralateral Breast in Patients with Diagnosed Unilateral Breast Cancer or High-Risk Lesions Radiology, June 1, 2007; 243(3): 670 - 680. [Abstract] [Full Text] [PDF]

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