Skip to main content

Advertisement

SpringerLink
Log in

Intraindividual, randomized comparison of the macrocyclic contrast agents gadobutrol and gadoterate meglumine in breast magnetic resonance imaging

  • Breast
  • Published:
European Radiology Aims and scope Submit manuscript

Abstract

Objectives

To compare intraindividually two macrocyclic contrast agents - gadobutrol and gadoterate meglumine (Gd-DOTA) - for dynamic and quantitative assessment of relative enhancement (RE) in benign and malignant breast lesions.

Methods

This was an ethically approved, prospective, single-centre, randomized, crossover study in 52 women with suspected breast lesions referred for magnetic resonance imaging (MRI). Each patient underwent one examination with gadobutrol and one with Gd-DOTA (0.1 mmol/kg BW) on a 1.5 T system 1 – 7 days apart. Dynamic, T1-weighted, 3D gradient echo sequences were acquired under identical conditions. Quantitative evaluation with at least three regions of interest (ROI) per lesion was performed. Primary endpoint was RE during the initial postcontrast phase after the first and second dynamic acquisition, and peak RE. All lesions were histologically proven; differences between the examinations were evaluated.

Results

Forty-five patients with a total of 11 benign and 34 malignant lesions were assessed. Mean RE was significantly higher for gadobutrol than Gd-DOTA (p < 0.0001). Gadobutrol showed significantly less washout (64.4 %) than Gd-DOTA (75.4 %) in malignant lesions (p = 0.048)

Conclusions

Gadobutrol has higher RE values compared with Gd-DOTA, whereas Gd-DOTA shows more marked washout in malignant lesions. This might improve the detection of breast lesions and influence the specificity of breast MRI-imaging.

Key Points

• Contrast agents differ in terms of peak enhancement and postinitial contrast behaviour.

• Gadobutrol results in greater peak RE in lesions, likely due to relaxivity.

• Gd-DOTA shows more pronounced washout in postinitial contrast behaviour of malignant lesions.

• Further investigations of the differences among GD-CM may improve sensitivity and specificity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Kuhl CK, Mielcareck P, Klaschik S et al (1999) Dynamic breast MR imaging: are signal intensity time course data useful for differential diagnosis of enhancing lesions? Radiology 211:101–110

    Article  CAS  PubMed  Google Scholar 

  2. Montemurro F, Martincich L, Sarotto I et al (2007) Relationship between DCE-MRI morphological and functional features and histopathological characteristics of breast cancer. Eur Radiol 17:1490–1497

    Article  PubMed  Google Scholar 

  3. Morris EA, Harms S (2004) ACR practice guideline for the performance of magnetic resonance imaging (MRI) of the breast. American College of Radiology, Reston (VA)

    Google Scholar 

  4. Heywang-Kobrunner SH, Viehweg P, Heinig A, Kuchler CH (1997) Contrast-enhanced MRI of the breast: accuracy, value, controversies, solutions. Eur J Radiol 24:94–108

    Article  CAS  PubMed  Google Scholar 

  5. Lehman CD, Isaacs C, Schnall MD et al (2007) Cancer yield of mammography, MR, and US in high-risk women: prospective multi-institution breast cancer screening study. Radiology 244:381–388

    Article  PubMed  Google Scholar 

  6. Saslow D, Boetes C, Burke W et al (2007) American Cancer Society Guidelines for Breast Screening with MRI as an Adjunct to Mammography. CA Cancer J Clin 57:75–89

    Article  PubMed  Google Scholar 

  7. Schelfout K, Van Goethem M, Kersschot E et al (2004) Preoperative breast MRI in patients with invasive lobular breast cancer. Eur Radiol 14:1209–1216

    Article  CAS  PubMed  Google Scholar 

  8. Van Goethem M, Schelfout K, Dijckmans L et al (2004) MR mammography in the pre-operative staging of breast cancer in patients with dense breast tissue: comparison with mammography and ultrasound. Eur Radiol 14:809–816

    Article  PubMed  Google Scholar 

  9. Mann RM, Kuhl CK, Kinkel K, Boetes C (2008) Breast MRI: guidelines from the European Society of Breast Imaging. Eur Radiol 18:1307–1318

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Flickinger FW, Allison JD, Sherry RM, Wright JC (1993) Differentiation of benign from malignant breast masses by time-intensity evaluation of contrast enhanced MRI. Magn Reson Imaging 11:617–620

    Article  CAS  PubMed  Google Scholar 

  11. Heywang SH, Hahn D, Schmidt H et al (1986) MR imaging of the breast using gadolinium-DTPA. J Comput Assist Tomogr 10:199–204

    Article  CAS  PubMed  Google Scholar 

  12. Kaiser WA, Zeitler E (1989) MR imaging of the breast: fast imaging sequences with and without Gd-DTPA. Preliminary Observations. Radiology 170:681–686

    Article  CAS  PubMed  Google Scholar 

  13. Stack JP, Redmond OM, Codd MB, Dervan PA, Ennis JT (1990) Breast disease: tissue characterization with Gd-DTPA enhancement profiles. Radiology 174:491–494

    Article  CAS  PubMed  Google Scholar 

  14. Weinmann HJ, Laniado M, Mutzel W (1984) Pharmacokinetics of GdDTPA/dimeglumine after intravenous injection into healthy volunteers. Physiol Chem Phys Med NMR 16:167–172

    CAS  PubMed  Google Scholar 

  15. Allard M, Doucet D, Kien P, Bonnemain B, Caille JM (1988) Experimental study of DOTA-gadolinium. Pharmacokinetics and pharmacologic properties. Investig Radiol 23:S271–S274

    Article  CAS  Google Scholar 

  16. Le Mignon MM, Chambon C, Warrington S, Davies R, Bonnemain B (1990) Gd-DOTA. Pharmacokinetics and tolerability after intravenous injection into healthy volunteers. Investig Radiol 25:933–937

    Article  Google Scholar 

  17. Bourasset F, Dencausse A, Bourrinet P, Ducret M, Corot C (2001) Comparison of plasma and peritoneal concentrations of various categories of MRI blood pool agents in a murine experimental pharmacokinetic model. MAGMA 12:82–87

    Article  CAS  PubMed  Google Scholar 

  18. Pintaske J, Martirosian P, Graf H et al (2006) Relaxivity of Gadopentetate Dimeglumine (Magnevist), Gadobutrol (Gadovist), and Gadobenate Dimeglumine (MultiHance) in human blood plasma at 0.2, 1.5, and 3 Tesla. Investig Radiol 41:213–221

    Article  Google Scholar 

  19. Rohrer M, Bauer H, Mintorovitch J, Requardt M, Weinmann H-J (2005) Comparison of magnetic properties of MRI contrast media solutions at different magnetic field strengths. Investig Radiol 40:715–724

    Article  Google Scholar 

  20. Attenberger UI, Runge VM, Morelli JN, Williams J, Jackson CB, Michaely HJ (2010) Evaluation of gadobutrol, a macrocyclic, nonionic gadolinium chelate in a brain glioma model: comparison with gadoterate meglumine and gadopentetate dimeglumine at 1.5T, combined with an assessment of field strength dependence, specifically 1.5 versus 3T. J Magn Reson Imaging 31:549–555

    Article  PubMed  Google Scholar 

  21. Knopp MV, Bourne MW, Sardanelli F et al (2003) Gadobenate dimeglumine-enhanced MRI of the breast: analysis of dose response and comparison with gadopentetate dimeglumine. AJR Am J Roentgenol 181:663–676

    Article  PubMed  Google Scholar 

  22. Martincich L, Faivre-Pierret M, Zechmann CM et al (2011) Multicenter, double-blind, randomized, intraindividual crossover comparison of gadobenate dimeglumine and gadopentetate dimeglumine for Breast MR imaging (DETECT Trial). Radiology 258:396–408

    Article  PubMed  Google Scholar 

  23. Pediconi F, Catalano C, Padula S et al (2008) Contrast-enhanced MR mammography: improved lesion detection and differentiation with gadobenate dimeglumine. AJR Am J Roentgenol 191:1339–1346

    Article  PubMed  Google Scholar 

  24. Gillis A, Gray M, Burstein D (2002) Relaxivity and diffusion of gadolinium agents in cartilage. Magn Reson Med 48:1068–1071

    Article  CAS  PubMed  Google Scholar 

  25. Wiener E, Woertler K, Weirich G, Rummeny EJ, Settles M (2007) Contrast enhanced cartilage imaging: Comparison of ionic and non-ionic contrast agents. Eur J Radiol 63:110–119

    Article  PubMed  Google Scholar 

  26. Marotta M, D'Armiento FP, Martino G et al (1985) Glycosaminoglycans in human breast cancer: morphological and biochemical study. Appl Pathol 3:164–169

    CAS  PubMed  Google Scholar 

  27. Olsen EB, Trier K, Eldov K, Ammitzboll T (1988) Glycosaminoglycans in human breast cancer. Acta Obstet Gynecol Scand 67:539–542

    Article  CAS  PubMed  Google Scholar 

  28. Takeuchi JSM, Sato E, Shamoto M, Miura K, Nakagaki S (1976) Variation in Glycosaminoglycan Components of Breast Tumors. Cancer Res 36:2133–2139

    CAS  PubMed  Google Scholar 

  29. van der Molen AJ, Bellin MF (2008) Extracellular gadolinium-based contrast media: differences in diagnostic efficacy. Eur J Radiol 66:168–174

    Article  PubMed  Google Scholar 

  30. Renz DM, Durmus T, Bottcher J et al (2014) Comparison of Gadoteric Acid and Gadobutrol for Detection as Well as Morphologic and Dynamic Characterization of Lesions on Breast Dynamic Contrast-Enhanced Magnetic Resonance Imaging. Investig Radiol. doi:10.1097/RLI.0000000000000039

    Google Scholar 

  31. Mussurakis S, Buckley DL, Coady AM, Turnbull LW, Horsman A (1996) Observer variability in the interpretation of contrast enhanced MRI of the breast. Br J Radiol 69:1009–1016

    Article  CAS  PubMed  Google Scholar 

  32. Committee ACoRB-R, Radiology ACo (2003) Breast imaging reporting and data system. American College of Radiology

  33. Li SP, Padhani AR, Taylor NJ et al (2011) Vascular characterisation of triple negative breast carcinomas using dynamic MRI. Eur Radiol 21:1364–1373

    Article  PubMed  Google Scholar 

  34. Veltman J, Mann R, Kok T et al (2008) Breast tumor characteristics of BRCA1 and BRCA2 gene mutation carriers on MRI. Eur Radiol 18:931–938

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Schmitz AC, Peters NH, Veldhuis WB et al (2008) Contrast-enhanced 3.0-T breast MRI for characterization of breast lesions: increased specificity by using vascular maps. Eur Radiol 18:355–364

    Article  CAS  PubMed  Google Scholar 

  36. Pediconi F, Catalano C, Occhiato R et al (2005) Breast lesion detection and characterization at contrast-enhanced MR mammography: gadobenate dimeglumine versus gadopentetate dimeglumine. Radiology 237:45–56

    Article  PubMed  Google Scholar 

  37. Pediconi F, Kubik-Huch R, Chilla B, Schwenke C, Kinkel K (2013) Intra-individual randomised comparison of gadobutrol 1.0 M versus gadobenate dimeglumine 0.5 M in patients scheduled for preoperative breast MRI. Eur Radiol 23:84–92

    Article  CAS  PubMed  Google Scholar 

  38. Anzalone N, Gerevini S, Scotti R, Vezzulli P, Picozzi P (2009) Detection of cerebral metastases on magnetic resonance imaging: intraindividual comparison of gadobutrol with gadopentetate dimeglumine. Acta Radiol 50:933–940

    Article  PubMed  Google Scholar 

  39. Ibrahim MA, Haughton VM, Hyde JS (1995) Effect of disk maturation on diffusion of low-molecular-weight gadolinium complexes: an experimental study in rabbits. AJNR Am J Neuroradiol 16:1307–1311

    CAS  PubMed  Google Scholar 

  40. Jansen SA, Shimauchi A, Zak L et al (2009) Kinetic curves of malignant lesions are not consistent across MRI systems: need for improved standardization of breast dynamic contrast-enhanced MRI acquisition. AJR Am J Roentgenol 193:832–839

    Article  PubMed Central  PubMed  Google Scholar 

  41. Pabst T, Kenn W, Kaiser WA, Hahn D (2001) Understanding why contrast enhancement in dynamic MRI is not reproducible: illustration with a simple phantom. Breast J 7:166–170

    Article  CAS  PubMed  Google Scholar 

  42. Sardanelli F, Fausto A, Esseridou A, Di Leo G, Kirchin MA (2008) Gadobenate dimeglumine as a contrast agent for dynamic breast magnetic resonance imaging: effect of higher initial enhancement thresholds on diagnostic performance. Investig Radiol 43:236–242

    Article  CAS  Google Scholar 

  43. Prince MR, Zhang HL, Roditi GH, Leiner T, Kucharczyk W (2009) Risk factors for NSF: a literature review. J Magn Reson Imaging 30:1298–1308

    Article  PubMed  Google Scholar 

  44. Sardanelli F, Boetes C, Borisch B et al (2010) Magnetic resonance imaging of the breast: recommendations from the EUSOMA working group. Eur J Cancer 46:1296–1316

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The scientific guarantor of this publication is Prof. Bernd Hamm. The authors of this manuscript declare relationships with the following companies: Prof. B. Hamm nearly all medical companies. Dr. A. Huppertz, Bayer Healthcare, Siemens Healthcare. Dr. E.M. Fallenberg, travel support and speaker’s fee by Bayer Healthcare, Guerbet, Siemens Healthcare, GE Healthcare. This study has received funding from Bayer Healthcare and Siemens Healthcare. The investigators had exclusive control of all data, manu- script drafting, and submission of this study. One of the authors has significant statistical expertise. Institutional review board approval was not required because the study was approved by the Federal Institute for Drugs and Medical Products and the local ethics committee (Clinical study phase: IIIb, EudraCT No.: 2009-013432-20). Written informed consent was obtained from all subjects (patients) in this study. Some study subjects or cohorts have been previously reported in Investigative Radiology. Renz DM, Durmus T, Bottcher J, Taupitz M, Diekmann F, Huppertz A, Pfeil A, Maurer MH, Streitparth F, Bick U, Hamm B, Fallenberg EM (2014) Comparison of Gadoteric Acid and Gadobutrol for Detection as Well as Morphologic and Dynamic Characterization of Lesions on Breast Dynamic Contrast-Enhanced Magnetic Resonance Imaging. Investigative Radiology. Methodology: prospective, randomised controlled trial, performed at one institution. We are grateful to Nikola Bangemann, MD, Tahir Durmus, MD, Elke Keil, MD, Christiane Richter-Ehrenstein, MD, Achim Schneider, MD and Klaus- Jürgen Winzer MD for their contribution in the patient recruitment and inclusion. We are thankful to Bettina Herwig for editorial support.

Author information

Authors and Affiliations

  1. Department of Radiology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Germany

    Eva M. Fallenberg, Diane M. Renz & Bernd Hamm

  2. Clinic of Radiation Therapy, Helios Clinics, Schwanebecker Chaussee 50, 13125, Berlin, Germany

    Bettina Karle

  3. SCOSSIS Statistical Consulting, Zeltinger Strasse 58, 13465, Berlin, Germany

    Carsten Schwenke

  4. Institute of Pathology, Charité Universitätsmedizin, Campus Charité Mitte, Charitéplatz 1, 10117, Berlin, Germany

    Barbara Ingod-Heppner

  5. Charite-Partner-Practice, Interdisciplinary Breast Center, Charité Universitätsmedizin, Rüdesheimer Platz 5, 14197, Berlin, Germany

    Angela Reles

  6. Department of Radiology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12203, Berlin, Germany

    Alexander Huppertz & Matthias Taupitz

  7. Department of Radiology, Charité - Universitätsmedizin Berlin, Charité Campus Mitte, Chariteplatz 1, 10113, Berlin, Germany

    Florian J. Engelken

Authors
  1. Eva M. Fallenberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Diane M. Renz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bettina Karle
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Carsten Schwenke
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Barbara Ingod-Heppner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Angela Reles
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Florian J. Engelken
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Alexander Huppertz
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Bernd Hamm
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Matthias Taupitz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eva M. Fallenberg.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fallenberg, E.M., Renz, D.M., Karle, B. et al. Intraindividual, randomized comparison of the macrocyclic contrast agents gadobutrol and gadoterate meglumine in breast magnetic resonance imaging. Eur Radiol 25, 837–849 (2015). https://doi.org/10.1007/s00330-014-3426-0

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00330-014-3426-0

Keywords

Search

Navigation