European Radiology

, Volume 13, Issue 12, pp 2688–2698 | Cite as

Currently used non-specific extracellular MR contrast media

Contrast Media
First Online:
Received:
Revised:
Accepted:

Abstract

Magnetic resonance contrast agents have demonstrated their clinical usefulness in a variety of organs for improved detection of various neoplastic, inflammatory and functional abnormalities. Gadolinium chelates are the most widely used. They are extracellular, non-specific contrast agents. Their use in many clinical indications is justified because, in conjunction with improved imaging techniques, these safe and image-enhancing contrast agents add morphologic and functional information compared with unenhanced MR images. This article describes the commercially available compounds, and summarizes their approval status on the international market regarding indications and doses. Their mechanisms of action, biodistributions, toxicities and tolerance profiles in normal and high-risk patient populations are described. Additionally, this article reviews the specific recommendations by the manufacturers for patients at risk. Finally, their main clinical applications are reviewed.

Keywords

Contrast media Gadolinium Magnetic resonance Contrast enhancement Safety 
This is a preview of subscription content, log in to check access.

References

  1. 1.
    Mathur-de Vré R, Lemort M (1995) Biophysical properties and clinical applications of magnetic resonance imaging contrast agents. Br J Radiol 68:225–247PubMedGoogle Scholar
  2. 2.
    Shellock FG, Kanal E (1999) Safety of magnetic resonance imaging contrast agents. J Magn Reson Imaging 10:477–484PubMedGoogle Scholar
  3. 3.
    Brash RB (1992) New directions in the development of MR imaging contrast media. Radiology 183:1–11PubMedGoogle Scholar
  4. 4.
    Brash RC, Weinmann HJ, Wesbey GE (1984) Contrast enhanced NMR imaging: animal study using gadolinium-DTPA complex. AJR 142:625–630Google Scholar
  5. 5.
    Van Beers BE, Gallez B, Pringot J (1997) Contrast-enhanced MR imaging of the liver. Radiology 203:297–306PubMedGoogle Scholar
  6. 6.
    Rinck PA, Muller RN (1999) Field strength and dose dependence of contrast enhancement by gadolinium-based MR contrast agents. Eur Radiol 9:998–1004PubMedGoogle Scholar
  7. 7.
    Tweedle MF, Wedeking P, Krishan K (1995) Biodistribution of radiolabeled, formulated gadopentetate, gadoteridol, gadoterate, and gadodiamide in mice and rats. Invest Radiol 30:372–380PubMedGoogle Scholar
  8. 8.
    Oksendal A, Hals P (1993) Biodistribution and toxicity of MR imaging contrast media. J Magn Reson Imaging 3:157–165PubMedGoogle Scholar
  9. 9.
    Chang C (1993) Magnetic resonance imaging contrast agents. Designs and physiochemical properties of gadodiamide. Invest Radiol 28 (Suppl 1):521–527Google Scholar
  10. 10.
    Cacheris W, Quay S, Rocklaye S (1980) The relationship between thermodynamics and the toxicity of gadolinium complexes. Magn Reson Imaging 8:467–481Google Scholar
  11. 11.
    Harpur E, Worah D, Hals P et al. (1993) Preclinical safety assessment and pharmacokinetics of gadodiamide injection: a new magnetic resonance imaging contrast agent. Invest Radiol 28:528–543Google Scholar
  12. 12.
    Tweedle MF, Ealon S, Eckelman W et al. (1988) Comparative chemical structure and pharmacokinetics of MRI contrast agents. Invest Radiol 23 (Suppl 1):236–239Google Scholar
  13. 13.
    Tweedle MF (1992) Physicochemical properties of gadoteridol and other magnetic resonance contrast agents. Invest Radiol 27 (Suppl 1):52–56Google Scholar
  14. 14.
    Runge VM, Parker JR (1997) Worldwide clinical safety assessment of gadoteridol injection: an update. Eur Radiol 7 (Suppl 5):243–245PubMedGoogle Scholar
  15. 15.
    Nelson KI, Gifford LM, Lauber-Huber C, Gross CA, Lasser TA (1995) Clinical safety of gadopentetate dimeglumine. Radiology 2:349–443Google Scholar
  16. 16.
    Niendorf HP, Haustein J, Cornelius I, Alhassan A, Clauss W (1991) Safety of gadolinium-DTPA: extended clinical experience. Magn Reson Med 22:222–228PubMedGoogle Scholar
  17. 17.
    Kanal E, Applegate G, Gillen C (1990) Review of adverse reactions, including anaphylaxis in 5260 cases receiving gadolinium-DTPA by bolus injection. Radiology 177:159Google Scholar
  18. 18.
    Tweedle MF (1997) The proHance story: the making of a novel MRI contrast agent. Eur Radiol 7 (Suppl 5):S225–S230Google Scholar
  19. 19.
    Yuh WTC, Parker JR, Carvlin MJ (1997) Indication-related dosing for resonance contrast media. Eur Radiol 7 (Suppl 5):S269–S275Google Scholar
  20. 20.
    Yuh WTC, Nguyen HD, Tali ET et al. (1994) Delineation of gliomas with various doses of MR contrast material. Am J Neuroradiol 15:983–989Google Scholar
  21. 21.
    Prince MR (1998) Contrast-enhanced MR angiography: theory and optimization. Magn Reson Imaging Clin North Am 6:257–267Google Scholar
  22. 22.
    Haustein J, Laniado M, Niendorf HP et al. (1993) Triple-dose versus standard-dose gadopentetate dimeglumine: a randomized study in 199 patients. Radiology 186:855–860PubMedGoogle Scholar
  23. 23.
    Yuh WTC, Fisher DJ, Engelken JD et al. (1991) MR evaluation of CNS tumors: dose comparison study with gadopentetate dimeglumine and gadoteridol. Radiology 180:485–491PubMedGoogle Scholar
  24. 24.
    Szopinski K, Szopinska M, Borowka A, Jakubovski W (2000) Magnetic resonance urography: initial experience of a low dose Gd-DTPA-enhanced technique. Eur Radiol 10:1158–1164PubMedGoogle Scholar
  25. 25.
    Olukotun AY, Parker JR, Meeks MJ, Lucas MA, Fowler DR, Lucas TR (1995) Safety of gadoteridol injection: US clinical trial experience. J Magn Reson Imaging 5:17–25PubMedGoogle Scholar
  26. 26.
    Cohan RH, Leder RA, Herzberg AJ et al. (1991) Extravascular toxicity of two magnetic resonance contrast agents: preliminary experience in the rat. Invest Radiol 26:224–226PubMedGoogle Scholar
  27. 27.
    Murphy KJ, Brunberg JA, Cohan RH (1996) Adverse reaction to gadolinium constrast media: a review of 36 cases. AJR 167:847–849Google Scholar
  28. 28.
    Niendorf HP, Alhassan A, Haustein J, Clauss W, Cornelius I (1993) Safety and risk of gadolinium-DTPA: extended clinical experience after more than 5,000,000 applications. Adv MRI Contrast 2:12–19Google Scholar
  29. 29.
    Runge VM (2000) Safety of approved MR contrast media for intravenous injection. J Magn Reson Imaging 12:205–213CrossRefPubMedGoogle Scholar
  30. 30.
    Eldevik OP, Brunberg JA (1994) Gadopentetate dimeglumine-enhanced MR of brain: clinical utility and safety in patients younger than two years of age. AJNR 15:1001–1008Google Scholar
  31. 31.
    Hanquiret S, Christope C, Greef DD, Gordon P, Perlemuller N (1996) Clinical evaluation of gadodiamide injection in pediatric MR imaging. Pediatric Radiol 26:806–810Google Scholar
  32. 32.
    Niess AC, Le Mignon MM, Vitry A, Caille JM (1991) Efficacité et tolérance du DOTA-Gd lors d'une enquête multicentrique européenne. Rev Im Med 3:383–387Google Scholar
  33. 33.
    Ball WJ, Nadel S, Zimmerman R et al. (1993) Phase III multicenter clinical investigation to determine the safety and efficacy of gadoteridol in children suspected of having neurologic disease. Radiology 186:769–774PubMedGoogle Scholar
  34. 34.
    Yoshikawa K, Davies A (1997) Safety of ProHance in special population. Eur Radiol 7 (Suppl 5):246–250CrossRefGoogle Scholar
  35. 35.
    Haustein J, Niendorf H, Krestin G et al. (1992) Renal tolerance of gadolinium-DTPA dimeglumine in patients with chronic renal failure. Invest Radiol 27:153–156Google Scholar
  36. 36.
    Bellin MF, Deray G, Assogba U et al. (1992) Gd-DOTA: evaluation of its renal tolerance in patients with chronic renal failure. Magn Reson Imaging 10:115–118PubMedGoogle Scholar
  37. 37.
    Tombach B, Bremer C, Reimer P et al. (2001) Renal tolerance of a neutral gadolinium chelate (gadobutrol) in patients with chronic renal failure: results of a randomized study. Radiology 218:651–657PubMedGoogle Scholar
  38. 38.
    Tombach B, Heindel W (2002) Value of 1.0 M gadolinium chelates: review of preclinical and clinical data on gadobutrol. Eur Radiol 12:1550–1556PubMedGoogle Scholar
  39. 39.
    Tombach B, Bremer C, Reimer P et al. (2002) Using highly concentrated gadobutrol as an MR contrast agent in patients also requiring hemodialysis: safety and dialysability. AJR 178:105–109PubMedGoogle Scholar
  40. 40.
    Schmiedl U, Maravilla K, Gerlach R, Dowling C (1990) Excretion of gadopentetate dimeglumine in human breast milk. AJR 154:1305–1306Google Scholar
  41. 41.
    Rojski N, Weinreb J, Lih A (1993) Quantitative analysis of gadopentetate dimeglumine excreted in breast milk. J Magn Reson Imaging 3:131–132PubMedGoogle Scholar
  42. 42.
    Kubik-Huch RA, Gottstein NM, Frenzel T et al. (2000) Gadopentetate dimeglumine excretion into human breast milk during lactation. Radiology 216:555–558PubMedGoogle Scholar
  43. 43.
    Colosimo C, Manfredi R, Tartaglione T (1997) Contrast-enhanced issues in the MR evaluation of the central nervous system. Eur Radiol 7 (Suppl 5):231–237PubMedGoogle Scholar
  44. 44.
    Hamm B, Thoeni RF, Gould RG et al. (1994) Focal liver lesions: characterization with nonenhanced and dynamic contrast-material-enhanced MR imaging. Radiology 190:417–423PubMedGoogle Scholar
  45. 45.
    Bartolozzi C, Lencioni R, Donati F, Cioni D (1999) Abdominal MR: liver and pancreas. Eur Radiol 9:1496–1512PubMedGoogle Scholar
  46. 46.
    Delorme S, Knopp MV (1998) Non-invasive vascular imaging: assessing tumour vascularity. Eur Radiol 8:517–527PubMedGoogle Scholar
  47. 47.
    Ho KY, Leiner T, de Haan MW, van Engelshoven JM (1999) Peripheral MR angiography. Eur Radiol 9:1765–1774PubMedGoogle Scholar
  48. 48.
    Mahfouz AE, Hamm B, Taupitz M (1997) Contrast agents for MR imaging of the liver: a clinical overview. Eur Radiol 7:507–513CrossRefPubMedGoogle Scholar
  49. 49.
    Saeed M, Higgings CB, Geschwind JF, Wendland MF (2000) T1-relaxation kinetics of extracellular, intracellular and intravascular MR agents in normal and acutely reperfused infarcted myocardium using echo-planar MR imaging. Eur Radiol 10:310–318PubMedGoogle Scholar
  50. 50.
    Sze G, Stimac GK, Barlett C et al. (1990) Multicenter study of gadopentetate dimeglumine as an MR contrast agent: evaluation in patients with spinal tumors. AJNR 11:967–974Google Scholar
  51. 51.
    Yamashita Y, Mitsuzaki K, Yi T et al. (1996) Small hepatocellular carcinoma in patients with chronic liver damage: prospective comparison of detection with dynamic MR imaging and helical CT of the whole liver. Radiology 200:79–84PubMedGoogle Scholar
  52. 52.
    Oi H, Mukarami T, Kim T et al. (1996) Dynamic MR imaging and early-phase helical CT for detecting small intrahepatic metastases of hepatocellular carcinoma. AJR 166:369–374Google Scholar
  53. 53.
    Scialpi M, Maggio A di, Midiri M, Loperfido A, Angelelli G, Rotondo A (2000) Small renal masses: assessment of lesion characterization and vascularity on dynamic contrast-enhanced MR imaging with fat suppression. AJR 175:751–757Google Scholar
  54. 54.
    Balci NC, Semelka RC, Patt RH et al. (1999) Complex renal cysts: findings on MR imaging. AJR 172:1495–1500Google Scholar
  55. 55.
    Saez F, Urresola A, Larena JA et al. (2000) Endometrial carcinoma: assessment of myometrial invasion with plain and gadolinium-enhanced MR imaging. J Magn Reson Imaging 12:460–466CrossRefPubMedGoogle Scholar
  56. 56.
    Kinoshita T, Ishii K, Naganuma H, Higashiiwai H (2000) MR findings of ovarian tumours with cystic components. Br J Radiol 73:333–339PubMedGoogle Scholar
  57. 57.
    Barentsz JO, Engelbrecht M, Jager GJ et al. (1999) Fast dynamic gadolinium-enhanced MR imaging of urinary bladder and prostate cancer. J Magn Reson Imaging 10:295–304PubMedGoogle Scholar
  58. 58.
    Hayashi N, Tochigi H, Shiraishi T, Takeda K, Kawamura J (2000) A new staging criterion for bladder carcinoma using gadolinium-enhanced magnetic resonance imaging with an endorectal surface coil: a comparison with ultrasonography. Br J Urol 85:32–36Google Scholar
  59. 59.
    Glockner JF (2001) Three-dimensional gadolinium-enhanced MR angiography: applications for abdominal imaging. RadioGraphics 21:357–370PubMedGoogle Scholar
  60. 60.
    White-Nunes L, Schnall MD, Orel SG et al. (1999) Correlation of lesion appearance and histologic findings for the nodes of a breast MR imaging interpretation model. RadioGraphics 19:79–92PubMedGoogle Scholar
  61. 61.
    Fisher U, Kopka L, Grabbe E (1999) Breast carcinoma: effect of preoperative contrast-enhanced MR imaging on the therapeutic apprach. Radiol 213:881–888PubMedGoogle Scholar
  62. 62.
    Hulka CA, Edmister WB, Smith BL et al. (1997) Dynamic echo-planar imaging of the breast: experience in diagnosing breast carcinoma and correlation with tumor angiogenesis. Radiology 205:837–842PubMedGoogle Scholar
  63. 63.
    van der Woude HJ, Verstraete KL, Hogendoorn PC, Taminiau AH, Hermans J, Bloem JL (1998) Musculoskeletal tumors: Does fast dynamic contrast-enhanced subtraction MR imaging contribute to the characterization? Radiology 208:821–828Google Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  1. 1.Department of RadiologyUniversity Paris XI, University Hospital Paul-Brousse AP-HP Villejuif CedexFrance
  2. 2.Department of RadiologyCentre Hospitalier Intercommunal de CréteilCréteil CedexFrance

Personalised recommendations