Amount of Retained Gadolinium ???
A well informed sufferer sent me this email some months bacK:
Years ago while trying to determine how much gadolinium someone might have in their body if they only retained 1% of the Gd in each dose of contrast they received, I found the following from Dr. Jerrold Abraham (SUNY).
Dr. Abraham estimated that everyone might retain between 1-2% of the gadolinium injected in each dose of contrast they received. http://www.upstate.edu/pathenvi/studies/cases/case10.php “However, it is noteworthy that even in persons with normal renal function, a small amount of the Gd from GBCA is apparently released into the body and stored in the bones, most likely incorporated into hydroxyapatite. In a single Gd-enhanced MRI scan a dose (0.1 mmol/kg body weight) on the order of 1.5 grams of Gd is injected intravenously; of this approximately 1% of the Gd (15 mg) may be released and deposited in bones. [This calculation is based on (1) the reported 98-99% clearance of Gd, (2) the demonstration of several micrograms Gd/g bone measured following GBCA administration, and (3) the assumption of total bone mass of approximately 10kg (see Abraham et al, Br J Derm, 2007)]"
Using that info, I did some calculations to determine how much Gd we might have in us if we only retained 1%. In my case, I received the same agent (Magnevist) for 5 MRIs and I know how much was administered each MRI (1 with 10 ml and 4 with 20 ml each) so I was able to do some calculations using what Dr. Abraham said as a guide. (My calculations for my 10 ml dose lined up with his estimate so I think I did it correctly).
1 mole of Gd = 157.25 grams so 1 mmol of Gd = 0.157 grams and Magnevist contains 0.5 mmol of Gd or 0.0786 grams. (Gadavist contains 1.0 mmol) I did not have to do calculations based on weight since I knew the dosage used for each of my MRIs. I would have received 0.786 grams of Gd for 1 MRI and a total of 6.288 grams for the other 4 – I received 7.074 grams of Gd for 5 MRIs.
1% of the Gd injected into me = 0.07074 grams OR 70.74 mg OR 70,740 mcg.
If I did the math correctly - If I only retained 1% and I excreted 1.0 mcg daily without provocation, it would take me approximately 194 years to eliminate it. I believe chelation therapy would have to significantly increase the amount of Gd excreted daily to do much good, but hopefully patients' symptoms would improve as their body burden of Gd is reduced over time.
Urine tests report results in mcg. From the results in our database, except for tests done within the first 2 or 3 months after an MRI, I believe that you are looking at less than 1.0 mcg per day for unprovoked tests and usually less than 0.5 mcg for tests performed more than 6 months after contrast administration. The agent administered and the number of doses of contrast can affect the results somewhat.
From the provoked test results in our database, IV chelation with EDTA or DTPA removes approximately 15 to 20 times more Gd than the patient was excreting on their own – it can be more than that if chelation is done soon after contrast administration or the patients had multiple MRIs with a linear agent. The amount excreted appears to remain higher than normal for a week or so after their treatments before dropping back down to near the patient’s pre-chelation level.
I hope that made sense and helps in some way.
My Response:
thanks for sharing this with all of us. Excellent calculation! I have done some of these calculations for others, and have seen others also do this. This actually is what scares me when I see patients with 20 or more GBCA injections and with GDD.
As complex as what you have written may seem to be, the truth actually is even much more complex. Each contrast agent will be different regarding how much is left behind and in what species- as the comparison between Omniscan and Dotarem illustrates, as the amount left behind is vastly greater after Omniscan. Renal function as measured by eGFR is a (the) primary influence in retained Gd - hence must factor into the calculation. There are multiple compartments in the body, all with different tenacity for hanging on to Gd. Then the difference between different species of Gd: intact chelate, salt, protein macromolecule. My opinion is the salt may be the least immunogenic, intact chelate in the middle, and the protein macromolecule. most immunogenic. This has not been experimentally shown. Le Chatelier's principle weighs heavily into the pathways of elimination. (everything strives for equilibrium) . The effects of chelation also last longer than just one day.
Ultimately, in the future, the best strategy may be initial iv chelations with DTPA or similar (note I never mention EDTA as it is a poor chelator for Gd) combined with immune system dampening, for bulk removal from the accessible reservoirs: skin, spleen, and white blood cells. Gd in the body may be present in mg amounts, and chelation with Gd shown in urine in the 10 mcg amounts (1/100). Le Chatelier results in re-equilibration from bone and brain back to these reservoirs, for enhanced removal in subsequent iv chelations.. Follow iv chelation with daily oral DTPA or similar (?HOPO) to essentially enhance the daily elimination fo Gd, probably for about 1 year.
Richard Semelka, MD
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