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Which Macrocyclic agent has the highest relaxivity?

There are three macrocyclic gadolinium based contrast agents (GBCAs) available on the Canadian market: gadobutrol (Gadovist®), gadoteriodol (ProHance®), and gadoterate meglumine (Dotarem®). As macrocyclic agents, these three GBCAs all belong to the most stable class of MRI contrast media.1 Beyond stability, there are other differences in molecular structure that impact the relaxivity of these agents and thus their ability to enhance signal intensity on the MR image. While the reported absolute relaxivity values have differed from study to study due to different measurement conditions, the order of relaxivity values has been consistent between studies with Gadovist® demonstrating consistently high relaxivity values across different magnetic field strengths (Figure 1).2-5

RI013 [EN] Relaxivity Matters - Which Macrocyclic agent has the highest relaxivity - no caption

Figure 1. T1 relaxivity (L mmol-1 s-1) of macrocyclic agents at 37˚C in A) bovine plasma (based on Rohrer M et al. 2005), B) human plasma (based on Noebauer-Huhmann IM et al. 2010), C) human whole blood (based on Shen Y et al. 2015), and D) human plasma (based on Szomolanyi P et al. 2019). The high relaxivity of Gadovist is generated by additional hydroxyl groups leading to better interaction with bulk water and higher water exchange rates.

Higher relaxivity is important as it can result in increased signal on T1-weighted images, enhanced image quality, and improved diagnostic confidence.6,7 In steady-state imaging where GBCA distribution in tissue and imaging time point contributes to signal enhancement, higher relaxivity leads to higher signal increase.8,9,11-143 In dynamic imaging (e.g. MR angiography), the image is obtained while the GBCA passes through a certain area. In this case, the signal is impacted by relaxivity as well as local tissue concentration and injected dose.7

Direct comparison studies have been conducted to investigate the effect of the high relaxivity of Gadovist® vs. the other macrocyclic GBCAs: gadoteridol and gadoterate meglumine. In 3 out of 4 direct comparison trials8-11 between Gadovist® and gadoteridol in contrast-enhanced MRI of the central nervous system (CE CNS MRI), Gadovist has demonstrated:

  • Greater contrast-enhancement and improved sensitivity and accuracy for detection of malignant disease8
  • Noninferiority of a single dose of Gadovist® versus a double dose of gadoteridol for detecting brain metastases9
  • Superior lesion-to-brain contrast and significantly higher rate of preference in contrast enhancement with Gadovist® versus gadoteridol11

Similarly, in 2 out of 3 direct comparison CE CNS MRI trials12-14 versus gadoterate meglumine, Gadovist® has demonstrated:

  • Higher lesion enhancement, and overall preference significantly in favor of Gadovist®13
  • Higher lesion signal intensity for imaging of acute inflammatory brain multiple sclerosis lesions14

References

  1. Frenzel et al. Invest Radiol. 2008;43:817-828
  2. Rohrer et al. Invest Radiol. 2005;40:715-724
  3. Noebauer-Huhmann et al. Invest Radiol. 2010;45:554-558
  4. Shen et al. Invest Radiol. 2015;50:330-338
  5. Szomolanyi et al. Invest Radiol. 2019 [Epub ahead of print]
  6. Essig et al. AJNR Am J Neuroradiol. 2012;33:803-817
  7. Kanal et al. AJNR Am J Neuroradiol. 2014;35:2215-2226
  8. Gutierrez et al. Magn Reson Insights. 2015;8:1-10
  9. Katakami et al. Invest Radiol. 2011;46:411-418
  10. Maravilla et al. AJNR Am J Neuroradiol. 2015;36:14-23
  11. Koenig et al. Eur Radiol. 2013;23:3287-3295
  12. Maravilla et al. AJNR Am J Neuroradiol. 2017;38:1681-1688
  13. Anzalone et al. Eur J Radiol. 2013;82:139-145
  14. Saake et al. Eur Radiol. 2016;26:820-828

 

Which Macrocyclic agent has the highest relaxivity?

There are three macrocyclic gadolinium based contrast agents (GBCAs) available on the Canadian market: gadobutrol (Gadovist®), gadoteriodol (ProHance®), and gadoterate meglumine (Dotarem®). As macrocyclic agents, these three GBCAs all belong to the most stable class of MRI contrast media.1 Beyond stability, there are other differences in molecular structure that impact the relaxivity of these agents and thus their ability to enhance signal intensity on the MR image. While the reported absolute relaxivity values have differed from study to study due to different measurement conditions, the order of relaxivity values has been consistent between studies with Gadovist® demonstrating consistently high relaxivity values across different magnetic field strengths (Figure 1).2-5

RI013 [EN] Relaxivity Matters - Which Macrocyclic agent has the highest relaxivity - no caption

Figure 1. T1 relaxivity (L mmol-1 s-1) of macrocyclic agents at 37˚C in A) bovine plasma (based on Rohrer M et al. 2005), B) human plasma (based on Noebauer-Huhmann IM et al. 2010), C) human whole blood (based on Shen Y et al. 2015), and D) human plasma (based on Szomolanyi P et al. 2019). The high relaxivity of Gadovist is generated by additional hydroxyl groups leading to better interaction with bulk water and higher water exchange rates.

Higher relaxivity is important as it can result in increased signal on T1-weighted images, enhanced image quality, and improved diagnostic confidence.6,7 In steady-state imaging where GBCA distribution in tissue and imaging time point contributes to signal enhancement, higher relaxivity leads to higher signal increase.8,9,11-143 In dynamic imaging (e.g. MR angiography), the image is obtained while the GBCA passes through a certain area. In this case, the signal is impacted by relaxivity as well as local tissue concentration and injected dose.7

Direct comparison studies have been conducted to investigate the effect of the high relaxivity of Gadovist® vs. the other macrocyclic GBCAs: gadoteridol and gadoterate meglumine. In 3 out of 4 direct comparison trials8-11 between Gadovist® and gadoteridol in contrast-enhanced MRI of the central nervous system (CE CNS MRI), Gadovist has demonstrated:

  • Greater contrast-enhancement and improved sensitivity and accuracy for detection of malignant disease8
  • Noninferiority of a single dose of Gadovist® versus a double dose of gadoteridol for detecting brain metastases9
  • Superior lesion-to-brain contrast and significantly higher rate of preference in contrast enhancement with Gadovist® versus gadoteridol11

Similarly, in 2 out of 3 direct comparison CE CNS MRI trials12-14 versus gadoterate meglumine, Gadovist® has demonstrated:

  • Higher lesion enhancement, and overall preference significantly in favor of Gadovist®13
  • Higher lesion signal intensity for imaging of acute inflammatory brain multiple sclerosis lesions14

References

  1. Frenzel et al. Invest Radiol. 2008;43:817-828
  2. Rohrer et al. Invest Radiol. 2005;40:715-724
  3. Noebauer-Huhmann et al. Invest Radiol. 2010;45:554-558
  4. Shen et al. Invest Radiol. 2015;50:330-338
  5. Szomolanyi et al. Invest Radiol. 2019 [Epub ahead of print]
  6. Essig et al. AJNR Am J Neuroradiol. 2012;33:803-817
  7. Kanal et al. AJNR Am J Neuroradiol. 2014;35:2215-2226
  8. Gutierrez et al. Magn Reson Insights. 2015;8:1-10
  9. Katakami et al. Invest Radiol. 2011;46:411-418
  10. Maravilla et al. AJNR Am J Neuroradiol. 2015;36:14-23
  11. Koenig et al. Eur Radiol. 2013;23:3287-3295
  12. Maravilla et al. AJNR Am J Neuroradiol. 2017;38:1681-1688
  13. Anzalone et al. Eur J Radiol. 2013;82:139-145
  14. Saake et al. Eur Radiol. 2016;26:820-828