MRI contrast agents (Gadolinium DTPA)
Gadolinium DTPA (diethylenetriamine penta-acetic acid) is one of the most common types of contrast agents used in magnetic resonance imaging (MRI). These agents are typically used to enhance the quality of the MRI images by altering the magnetic properties of nearby water molecules, which improves the visibility of certain tissues, blood vessels, and pathological changes in the body.
MRI contrast agents
Chemistry of Gadolinium DTPA
Gadolinium DTPA belongs to a class of compounds known as gadolinium-based contrast agents (GBCAs). Gadolinium is a rare earth metal with strong paramagnetic properties, which makes it particularly useful in MRI. However, gadolinium ions are toxic when free in the body, so they are chelated (bound) to DTPA, a chelating agent. This chelation forms a stable complex that prevents the gadolinium from being deposited in the body and ensures it is safely excreted after the procedure.
How MRI Contrast Agents Work
Gadolinium DTPA enhances these images in two ways:
- Paramagnetic Properties: Gadolinium ions are paramagnetic, meaning they have unpaired electrons that enhance the magnetic properties of the atoms nearby. When gadolinium DTPA is injected into the body, it temporarily alters the magnetic properties of nearby water molecules.
- Shortening Relaxation Times: The most significant effect of gadolinium is its ability to shorten the T1 relaxation time of nearby water protons. T1 relaxation time is the time it takes for protons to realign with the magnetic field after being disturbed by the radiofrequency pulse. By shortening this time, gadolinium increases the brightness (signal intensity) of certain tissues in the resulting images. This increased signal intensity helps to clearly differentiate between normal and abnormal tissues, particularly useful in detecting tumors, inflammation, and vascular diseases.
Non contrast brain MRI
Contrast enhanced brain MRI
Understanding MRI Contrast Agents: Linear vs Macrocyclic Agents
Contrast agents in MRI are classified into two main categories: linear and macrocyclic agents, based on their molecular structure.
Linear Agents: These GBCAs have a linear molecular structure. The gadolinium ion is held within a linear chelating agent, which is less stable compared to its macrocyclic counterpart. This structure can sometimes result in a higher rate of gadolinium release into the body, which has raised concerns regarding safety, especially in patients with severe renal dysfunction. Here is a list of linear contrast agents:
- Gadopentetate dimeglumine (Magnevist) – Manufactured by Bayer (Note: This agent has been withdrawn from the market in some countries due to safety concerns.)
- Gadodiamide (Omniscan) – Manufactured by GE Healthcare
- Gadoversetamide (OptiMARK) – Manufactured by Mallinckrodt
Macrocyclic Agents: These agents have a gadolinium ion that is encased in a cyclic chelating agent. This configuration tends to be more stable than the linear form, which means it’s less likely to release gadolinium ions into the body. Macrocyclic agents are generally considered safer, particularly for patients with kidney issues, as they have a lower risk of causing gadolinium deposition disease. Here is a list of Macrocyclic Contrast Agents:
- Gadoteridol (ProHance) – Manufactured by Bracco
- Gadobutrol (Gadavist, Gadovist) – Manufactured by Bayer
- Gadoterate meglumine (Dotarem) – Manufactured by Guerbet
Hepatocellular-specific MRI Contrast Agents
These are a specific type of GBCAs used primarily to enhance images of the liver. They are taken up by the liver’s hepatocytes, providing better contrast and making it easier to distinguish between healthy and diseased tissue. This specialization allows for improved detection and characterization of liver lesions and diseases.
- Gadoxetate disodium (Eovist, Primovist) – As noted above, manufactured by Bayer and used specifically for liver imaging. Here is a list of hepatocellular-specific contrast agents.
- Gadobenate dimeglumine (MultiHance) – Manufactured by Bracco; this agent is used for both general contrast enhancement and liver-specific imaging.
Alternative MRI Contrast Agents without Gadolinium-Based Components
Superparamagnetic Iron Oxide (SPIO) and Ultrasmall Superparamagnetic Iron Oxide (USPIO):
Mechanism: These agents contain iron oxide and affect the magnetic susceptibility of nearby tissues, mainly used for liver imaging.
Common Types:
- Ferumoxides (Feridex I.V.)
- Ferumoxytol (Feraheme)
- Iron oxide nanoparticles (Sinerem)
Manganese-Based Agents:
Mechanism: Manganese enhances the contrast in MRIs by shortening the relaxation time of tissues, particularly in the liver and pancreas.
- Common Types: Mangafodipir (Teslascan)
References
- Thian, Y. L., Riddell, A. M., & Koh, D. M. (2013). Liver-specific agents for contrast-enhanced MRI: role in oncological imaging. Cancer Imaging, 13(4), 567–579. doi: 10.1102/1470-7330.2013.0050.
- Lv, J., Roy, S., Xie, M., Yang, X., & Guo, B. (2023). Contrast Agents of Magnetic Resonance Imaging and Future Perspective. Nanomaterials (Basel), 13(13), 2003. doi: 10.3390/nano13132003
- Bayer AG. (2020, November). Gadovist® Product Monograph. Retrieved from https://www.bayer.com/sites/default/files/2020-11/gadovist-pm-en_0.pdf
- Guerbet. (n.d.). Dotarem Prescribing Information. Retrieved from https://www.guerbet.com/media/d3mpn2kg/dotarem-prescribing-information.pdf?uri=urn:aaid:scds:US:716f3850-2488-4f71-b10f-2d623c96e9ad
- FDA. (2010). Highlights of Prescribing Information: Gadopentetate Dimeglumine (Magnevist) Injection, for intravenous use [PDF]. Retrieved from https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022090s004lbl.pdf
- Xiao, Y.-D., Paudel, R., Liu, J., Ma, C., Zhang, Z.-S., & Zhou, S.-K. (2016). MRI contrast agents: Classification and application (Review). International Journal of Molecular Medicine, 38(5), 1319–1326. https://doi.org/10.3892/ijmm.2016.2744