A Closer Look at Gadolinium-Related Nephrogenic Systemic Fibrosis (NSF) also known as Nephrogenic Fibrosing Dermopathy (NFD)

Armand Rossetti

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For example, the Prohance brand of Gadolinium is more stable than and clears more completely than the Omniscan brand of Gadolinium. This difference in stability is due to the chemical structure of the two different brands of Gadolinium contrast agent. Prohance is a non-linear form of gadolinium where the organic protective shell (the chelate) is attached in four places around the gadolinium. With Omniscan, we have a linear complexed coating. What does this mean?

The body attacks the Omniscan shell mush easier because it is easier to break single linear bonds than it is to break four bonds that form around the Prohance brand gadolinium Evidently, GE Healthcare was aware of this problem because it included extra chelating agent in with the Omniscan contrast agent in an attempt to reduce the chance of free gadolinium3+ (which is very toxic) to remain behind in the system. Bracco Diagnostics manufacturers Prohance. (
The 9.22 minute point in the video (the second of four grand rounds presentations) is where this important NSF/gadolinium discussion begins.

Here is a series of four figures that you may review by clicking on “next figure” at the top and right side of each figure frame. Notice that Figure 1 represents a long term manifestation of NSF. That contrasts with Figure 2, which shows early signs of NSF. Figure 3 displays a histopathology slide of the usual thickened skin that results from free gadolinium poisoning. For comparison, (here is a slide representing normal skin [or dermis]). Figure 4 shows how the gadolinium causes an increase in interstitial mucin. You can see the introduction of fibrocytes and swollen collagen bundles and a degeneration of collagen fibers. Notice, as well, the absence of inflammatory cells. Lastly, here is a chart showing characteristics of several brands of gadolinium contrast agents. Notice that Omniscan contains 48 times more excess chelate content than Prohance, and that Optimark has added nearly 120 times more excess chelate than Prohance.

Diagnostic bone scans (third through fifth pictures) have revealed that gadolinium accumulates predominately in the lower and distal upper extremities. Taking a further look using T1 and T2 axial tomography (last two pictures) shows NSF affecting both skeletal muscle and skin. There is a symmetric skin thickening and evidence of edema in the medial thighs. One can also detect edema in the subcutaneous fat, intramuscular fascia, and thigh muscles. Interestingly, there is some sparing of the posterior thigh muscles. For comparison, Here is an axial tomography of an otherwise normal thigh (except for a fractured femur).

The Chemistry behind Complexed Gadolinium Contrast Agent:

A paper entitled, Contrast Agents in Magnetic Resonance Imaging (Andrei Volkov 1997) provides a comprehensive look at gadolinium complexation and resulting stability. The Volkov paper also addresses among other phenomena, in vivo gadolinium toxicity and Transmetallation including its connection with toxicity.

Conclusion:

While all gadolinium contrast agents may contribute to the manifestation of NSF, some gadolinium agents may be less risky than others, due to the way in which the ligands (coating elements) are attached to the gadolinium itself.

Certain manufacturers seem to be aware that some more structurally stable chemical compositions of ligand treated gadolinium contrast agents are less risky than others. Knowledge of a range of stability for the different gadolinium contrast agent brands is evident because those manufacturers of the less stable coated agents have added free chelating agents to their particular brand of contrast solution.

GE Healthcare’s Omniscan brand of gadolinium contrast agent is a good example of a weaker linear-type bonded chelate (see the grand rounds presentation linked above). Because of the nature of the chelate bonding, the linear compounds are prone to breakdown and release of free and highly toxic gadolinium3+ from the safer chelated form, before elimination from the body. Omniscan contains unbonded chelating agent, which GE Healthcare has added to the solution in the hope of preventing early and toxic free gadolinium release.

Early release of free gadolinium from the chelated form, and perfusion of the free gadolinium into the body's tissues usually results in NSF.