Skip to main content
Log in

Safety of contrast-enhanced MR angiography employing gadobutrol 1.0 M as contrast material

European Radiology Aims and scope Submit manuscript

Abstract.

Our objectives were to evaluate the safety of intravenous 1.0-m gadobutrol injections in patients with an indication for contrast-enhanced magnetic resonance angiography (CE MRA) of supra-aortal, pelvic, or peripheral arteries by examining and assessing adverse events, laboratory values, vital signs and ECG findings for clinical significance. In 435 patients, recruited in three multicenter trials for safety evaluations of the new contrast agent 1.0-m gadobutrol, CE MRA was performed with 1.0- to 1.5-T scanners using three-dimensional gradient-echo sequences and phased-array coils. The study population comprised 312 men and 123 women with a mean age of 60.9 years. Two hundred seven patients had an indication for imaging of body arteries and 228 had an indication for imaging of peripheral arteries. Blood laboratory values and urinalysis results of 124 patients as well as heart rate, blood pressure, and 12-lead-electrocardiogram readings of 93 patients obtained during a follow-up period of up to 72 h after the injection of contrast media were available for safety analysis. Contrast media application was performed as intravenous bolus injection of 1.0-m gadobutrol in fixed doses according to the patients' body weight (b.w.) and indication for CE MRA and was followed by a 20- to 40-ml saline flush. Mean dose actually applied was 0.1 0.27 mmol/kg b.w. Flow rate ranged between 0.2 and 2.0 ml/s. Safety evaluations found a good tolerability with only 4.6% of at least "possibly related" adverse reactions and no clinically relevant changes in blood and urine samples including no transmetallation effect on serum zinc values. Analysis of renal tolerance showed no influence on renal function irrespective of preexisting renal impairment. The ECG analysis (rhythm analysis, pace-setting disturbances, conduction disturbances, and time interval measurements, including uncorrected and corrected QT) showed no clinically relevant effect of the injection of 1.0-m gadobutrol on the cardiac conduction system. Intravenous injection of 1.0-m gadobutrol at a dose of up to 0.1 0.27 mmol/kg b.w. in the indication CE MRA is safe and causes no clinically relevant changes in safety parameters such as heart rate, blood pressure, blood and urine laboratory values, and cardiac conduction system.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Niendorf HP, Alhassan A, Balzer T, Clauss W, Geens V (1994) Safety and risk of gadolinium-DTPA: extended clinical experience after more than 20 million applications. Invest Radiol 29 (Suppl 2):179–182

    Article  Google Scholar 

  2. Tweedle MF, Hagan JJ, Kumar K, Mantha S, Chang CA (1991) Reaction of gadolinium chelates with endogenously available ions. Magn Reson Imaging 9:409–415

    Article  CAS  PubMed  Google Scholar 

  3. Prince MR, Narasimham DL, Stanley JC, Chenevert TL, Williams DM, Marx MV, Cho KJ (1995) Breath-hold gadolinium-enhanced MRA of the abdominal aorta and its major branches. Radiology 197:785–792

    Article  CAS  PubMed  Google Scholar 

  4. Holland GA, Dougherty L, Carpenter JP, Golden MA, Gilfeather M, Slossman F, Schnall MD, Axel L (1996) Breath-hold ultrafast 3D gadolinium-enhanced MRA of the aorta and the renal and other visceral abdominal arteries. Am J Roentgenol 166:971–981

    Article  CAS  Google Scholar 

  5. Prince MR (1996) Body MRA with gadolinium contrast agents. Magn Reson Imaging Clin North Am 4:11–24

    CAS  Google Scholar 

  6. Mitsuzaki K, Yamashita Y, Ogata I, Tang Y, Namimoto T, Takahashi M (1999) Optimal protocol for injection of contrast material at MRA: study of healthy volunteers. Radiology 213:913–918

    Article  CAS  PubMed  Google Scholar 

  7. Fellner F, Janka R, Dobritz M, Lenz M, Lang W, Bautz W (1999) Gd-BOPTA: The MRA contrast agent of choice? Röntgenpraxis 52:51–58

  8. Knopp MV, Floemer F, Schoenberg SO, Bock M, Tengg Kobligk H von, Hentrich R, Lodemann K, Kaick G von (1999) Does a weakly binding Gd-chelate improve MR angiography? Initial findings using Gd-BOPTA for multiphasic 3D MRA. Proc Int Soc Magn Reson Med 7:1208

    Google Scholar 

  9. Leung DA, Hany TF, Debatin JF (1998) Three-dimensional contrast-enhanced magnetic resonance angiography of the abdominal arterial system. Cardiovasc Intervent Radiol 21:1–10

    Article  CAS  PubMed  Google Scholar 

  10. Schoenberg S, Bock M, Knopp MV, Essig M, Laub G, Hawighorst H, Zuna I, Kallinowski F, Kaick G von (1999) Renal arteries: optimization of three-dimensional gadolinium-enhanced MR angiography with bolus-timing-independent fast multiphase acquisition in a single breath hold. Radiology 211:667–679

    Article  CAS  PubMed  Google Scholar 

  11. Tombach B, Heindel W (2002) Value of 1.0 M gadolinium chelates: review of preclinical and clinical data on gadobutrol. Eur Radiol 12:1550–1556

    Article  PubMed  Google Scholar 

  12. Priebe M, Mohr A, Brossmann J, Heller M, Fraham C (2002) Gadobutrol: an alternative contrast agent for digital subtraction dacryocystography. Eur Radiol 12:2083–2086

    Article  CAS  PubMed  Google Scholar 

  13. Runge VM, Parker JR (1997) Worldwide clinical assessment of gadoteridol injection: an update. Eur Radiol 7 (Suppl 5):243–245

    Article  PubMed  Google Scholar 

  14. Nelson KL, Gifford LM, Lauber-Huber C, Gross CA, Lasser TA (1995) Clinical safety of gadopentetate dimeglumine. Radiology 196:439–443

    Article  CAS  PubMed  Google Scholar 

  15. Puttagunta NR, Gibby WA, Puttagunta VL (1996) Comparative transmettallation kinetics and thermodynamic stability of gadolinium-DTPA bis-glucosamide and other magnetic resonance imaging contrast media. Invest Radiol 31:619–624

    Article  CAS  PubMed  Google Scholar 

  16. Corot C, Idee JM, Hentsch AM, Santus R, Mallet C, Goulas V, Bonnemain B, Meyer D (1998) Structure-activity relationship of macrocyclic and linear gadolinium chelates: investigation of transmetallation effect on the zinc-dependent metallopeptidase angiotensin-converting enzyme. J Magn Reson Imaging 8:695–702

    Article  CAS  PubMed  Google Scholar 

  17. Puttagunta NR, Gibby WA, Smith GT (1996) Human in vivo comparative study of zinc and copper transmetallation after administration of magnetic resonance imaging contrast agents. Invest Radiol 12:739–742

    Article  Google Scholar 

  18. Tombach B, Bremer C, Reimer P, Kisters K, Schaefer RM, Geens V, Heindel W (2001) Renal tolerance of a neutral Gadolinium chelate (gadobutrol) in patients with chronic renal failure: results of a randomized study. Radiology 218:651–657

    Article  CAS  PubMed  Google Scholar 

  19. Prince MR, Arnoldus C, Frisoli JK (1996) Nephrotoxicity of high dose gadolinium compared with iodinated contrast. J Magn Reson Imaging 1:162–166

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jörn O. Balzer.

Additional information

Further centers contributing to the total number of patients (no Lab and/or ECG), (alphabetical):

Klinikum Charité, Campus Mitte, Med. Fakultät der Humboldt Universität Berlin, Abt. für Radiologie (Dr. Kopka, Dr. Rodenwaldt)

Klinikum der Albert Ludwig Universität Freiburg, Abt. für Röntgendiagnostik (Dr. Winterer, Dr. Laubenberger)

Glasgow Royal Infirmary, x-ray department (Dr. Leen)

Universitätsklinik Graz, Gemeinsame Einrichtung MR (Dr. Aschauer, Prof. Ebner)

Zentralinstitut für bildgebende Diagnostik, Städtisches Klinikum Karlsruhe (Prof. Reimer, Dr. Rehm, Dr. Gregor)

Klinik für Radiologische Diagnostik, Christian Albrecht Universität Kiel (Dr. Schäfer, Dr. Brosmann, Prof. Heller)

Klinikum Johannes Gutenberg Universität Mainz, Klinik und Poliklinik für Radiologie (Dr. Oberholzer, Dr. Kreitner)

Klinikum der Universität Regensburg, Institut für Röntgendiagnostik (Dr. Altjohann, Prof. Link)

Royal Hallamshire Hospital Sheffield, Academic Department of Radiology (Prof PD Griffiths)

Universitätsspital Zürich, Institut für Diagnostische Radiologie (Dr. Weishaupt, Dr. Hilfiker, Prof. Marincek)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Balzer, J.O., Loewe, C., Davis, K. et al. Safety of contrast-enhanced MR angiography employing gadobutrol 1.0 M as contrast material. Eur Radiol 13, 2067–2074 (2003). https://doi.org/10.1007/s00330-002-1768-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00330-002-1768-5

Keywords.

Navigation