Some years ago, I saw a new patient who was worried about having a multiparametric MRI (mpMRI) to find out if he had prostate cancer (PCa). Ironically, he was less troubled about the cancer than the scan, since we planned to use a contrast agent containing the element gadolinium. You see, in 2013 a Japanese study raised concern that gadolinium-based contrast agents (GBCAs) leave deposits in the brain. Once radiologists started looking for it, they indeed found gadolinium stains on the brain.
Who would want to go through a possible life-saving scan if they thought they it caused brain damage? I would certainly think twice, so I could understand my patient’s concern.
The problem was, experts could not agree if these areas posed a health risk. One radiologist from the Mayo Clinic noted that if there was a damaging effect, it would already have been noticed, since “…upward of 400 million doses of gadolinium agents have been given since we started using them almost 30 years ago, and if there was something toxic, we would have seen it by now.”[i] In 2015, the FDA issued a bulletin that basically said, we just don’t know.
Concern about kidney function
However, there is another problem that touches upon mpMRI of the prostate. Years before the brain scare, a 2006 Danish study picked up a risk of using GBCAs if kidney function was impaired. This was a genuine concern, since compromised kidneys may not be able to flush out all gadolinium in spite of chelation.
For mpMRI of the prostate, using contrast is a value-added measure that can clarify what other sequences sometimes leave somewhat ambiguous. So, let’s examine the GBCA pros and cons:
- PRO – In multiparametric MRI of the prostate, only one imaging sequence uses contrast in order to improve the visibility of a tumor’s blood supply. Cancer builds its own blood vessels to supply it with oxygen and nutrients, but these tumor blood vessels are don’t behave normally. With gadolinium, we can identify the presence and likely aggression level of a cancerous tumor based on the visibility of blood flow in tumor vessels.
- CON – Gadolinium is classified as a rare earth and, by itself, it would be toxic.
- PRO – When used as a contrast agent, gadolinium is bonded molecularly to a special substance called a chelating agent, or chelate. Chelation safely keeps gadolinium from toxic interaction with other molecules in the body, and makes it water-soluble so the body can flush it out.
- CON – There are two different types of chelates, linear and macrocyclic. How do we know if one is safer than the other?
Linear and macrocyclic chelates
When bonding gadolinium atoms with other molecules, there are two possible molecular structures that can form. One of them, called linear, forms an open, mobile chain that has no strong binding to the toxic capacity of certain gadolinium ions, whereas the other structure is stronger because it is more like a rigid ring, so it is called macrocyclic. It appears that the deposits left in the brain were due linear chelates with their weaker bonds allowed gadolinium to be released from its chelate.
Overall safety of GBCA and a preference for macrocyclic chelates
An October, 2020 study by a multinational, interdisciplinary team explored possible safety issues using GBCAs with cardiac patients. It’s important to note that in 2017, the European Medicines Agency (EMA) mandated the use of macrocyclic GBCAs rather than linear because of growing evidence that linear agents were more likely to leave deposits in the body. In addition, the study looked for adverse effects such as allergic reactions to GBCA. The team had access to over 150,000 cardiovascular case records from Jan. 2013 – Oct. 2019, of whom 145,855 patients (nearly 95%) had an MRI with GBCA contrast. After 2017, less than 1% of those had linear GBCAs.
As reported in Diagnostic Imaging’s online newsletter:
Based on their analysis of patient outcomes, the team identified acute adverse events (AAEs) and classified them as mild, moderate, or severe. Overall, they discovered 556 AAEs among patients who had contrast-enhanced exams (0.38 percent), and only 47 were classified as severe or life-threatening. And, fewer AAEs were associated with macrocyclic GBCAs versus linear GBCAs.[ii]
Less than a half percent of adverse events, some of which were related to drugs the cardiac patients were using, is greatly reassuring.
Today, we still don’t know the long-term effect of gadolinium stains on the brain, but we do know that individuals who undergo numerous MRI scans using GBCAs, such as multiple sclerosis patients, are more likely to develop them. At our Center, we put patient safety first, including qualifying patients for GBCA use. For those with sub-par kidney function, we recommend what is called a biparametric MRI (bpMRI) that does not use a contrast agent yet is highly accurate. And, we use only macrocyclic GBCAs. We specialize in prostates, but rest assured, we take no chances with kidneys, brains, or any other body part.
NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.
[i] Orenstein, Beth. Gadolinium on the Brain: Curiosity or Cause for Concern? Radiology Today. Vol. 17 No. 7 P. 20. https://www.radiologytoday.net/archive/rt0716p20.shtml
[ii] Palmer, Whitney J. “Gadolinium Carries Low Adverse Event Risk for Cardiac MRI.” Diagnostic Imaging. Oct. 29, 2020. https://www.diagnosticimaging.com/view/gadolinium-carries-low-adverse-event-risk-for-cardiac-mri