Gadolinium Distribution in the Kidney, Liver, and Heart of Wistar Rats after Administration of Gadolinium-Based Contrast Agents
Abstract:
Magnetic resonance
imaging (MRI) is an established non-invasive and non-destructive medical imaging
modality for the assessment of various organ systems in the human body. Gadolinium-Based
Contrast Agent (GBCA) enhanced and improved images from MRI and was believed to
be entirely excreted through urine in normal kidney function within 24 hours after
injection. Previous studies identified gadolinium accumulations in the brain, bones,
and skin of animals. This study evaluated gadolinium retention in normal kidneys,
Liver, and heart of Wistar rats after administration of GBCAs in male Wistar rats.
Twenty-five male Wistar rats of ages ≥ 5 weeks or ≤ 6 weeks in 4 experimental and
1 control groups were studied. Ethical considerations were obtained from the Institutional
Review Board (IRB) of the Nigerian Institute of Medical Research (NIMR), Nigeria.
Samples in experimental groups each administered 2.5 mls of 4 different GBCAs, and the control group same per day of saline
intravenously through the lateral tail for five days a week and continued for 4 weeks. The kidney, Liver,
and Heart tissues of these samples were harvested 4 weeks after the last injection
and sent for spectrometry evaluation. Samples in the control group had no gadolinium
accumulation. Groups administered gadopentetate dimeglumine, and gadodiamide had greater cardiac metrics (0.397
and 0.390). The higher renal metric was experienced by samples that received dotarem
and cyclolux (0.397 and 0.377), though the sample exposed to cyclolux reported
more Liver metric (0.407) than other concentrations. Wistar rats’ Kidneys, Liver,
and Heart retained gadolinium weeks after injection of GBCAs.
References:
[1] Yadollahpour,
A., Venkateshwarlu, G., 2016, Applications of gadolinium nanoparticles in magnetic
resonance imaging: A review on recent advances in clinical imaging. International
Journal of Pharmacology and Technology, 8: 11379-11393.
[2] Perazella,
M., 2009, Status of gadolinium toxicity
in patients with kidney disease. Clinical Journal of American Society of Nephrology,
4,461-469.
[3] Ramalho,
J., Semelka, R.C., Ramalho, M., Nunes, R., Obaidy, M.A.I., Castillo, M., 2016, Gadolinium-based
Contrast Agent Accumulation and Toxicity: An Update. American Journal of Neuroradiology.
37(7),1192-1198.
[4] Leyba, K.., Wagner, B., 2019, Gadolinium-based
contrast agents: why nephrologists need to be concerned. Current Opinion in Nephrology and Hypertension,
28(2),154–162. https://doi.org/10.1097/MNH.0000000000000475
[5] Rogosnitzky,
M., Branch, S., 2016, Gadolinium-based contrast agent toxicity: a review of known
and proposed mechanisms. Biometals
29,365–376 https://doi.org/10.1007/s10534-016-9931-7.
[6] Quattrocchi, C. C., van der Molen, A.
J. ,2017, Gadolinium Retention in the Body and Brain: Is It Time for an International
Joint Research Effort?. Radiology,
282(1),12–16. https://doi.org/10.1148/radiol.2016161626.
[7] Gale, E. M., Caravan, P., 2018, Gadolinium-Free
Contrast Agents for Magnetic Resonance Imaging of the Central Nervous System. ACS Chemical Neuroscience, 9(3), 395–397. https://doi.org/10.1021/acschemneuro.8b00044.
[8] Kanda, T., Fukusato, T., Matsuda, M.,
Toyoda, K., Oba, H., Kotoku, J., Haruyama, T., Kitajima, K., Furui, S., 2015a, Gadolinium-based
Contrast Agent Accumulates in the Brain Even in Subjects without Severe Renal Dysfunction:
Evaluation of Autopsy Brain Specimens with Inductively Coupled Plasma Mass Spectroscopy.
Radiology, 276(1), 228–232. https://doi.org/10.1148/radiol.2015142690.
[9] Radbruch, A., Weberling, L.D., Kieslich,
P.J., Eidel, O., Burth, S., Kickingereder, P., Heiland, S., Wick, W., Schlemmer,
H., Bendszus., 2015, Gadolinium retention in the dentate nucleus
and globus pallidus is dependent on the class of contrast agent. Radiology 275:783–791.
[10] Kanda, T., Ishii, K., Kawaguchi, H.,
Kitajima, K., Takenaka, D., 2014, High signal intensity in the dentate nucleus and
globus pallidus on unenhanced T1-weighted MR images: relationship with increasing
cumulative dose of a gadolinium-based contrast material. Radiology, 270(3),834–841. https://doi.org/10.1148/radiol.13131669.
[11] Khairinisa,
M. A., Takatsuru, Y., Amano, I., Erdene, K., Nakajima, T., Kameo, S., Koyama, H.,
Tsushima, Y., Koibuchi, N., 2018, The Effect of Perinatal Gadolinium-Based Contrast
Agents on Adult Mice Behavior. Investigative
Radiology, 53(2), 110–118.
[12] Pass, D., Freeth, G.,1993, The rat. Anzccart
News. 6,1–4.
[13] Quinn, R., 2005, Comparing rats to human’s age: How old
is my rat in people years? Nutrition.
21:775–7.
[14] Sengupta, P., 2012, A Scientific Review of Age Determination
for a Laboratory Rat: How old is it in comparison with Human age? Biomedical
International, 2,81–9.
[15] Mugikura, S., Takase, K., 2017, Fear
of linear gadolinium-based contrast agents and the Japanese radiologist’s choice.
Japanese Journal of Radiology. 35(11), 695–696.
[16] Davidson, M. K., Lindsey, J. R., Davis,
J. K., 1987, Requirements and selection of an animal model. Israel Journal of Medical Sciences, 23(6), 551–555.
[17] Sengupta, P., 2013, The Laboratory Rat:
Relating Its Age with Human’s. International
Journal of Preventive Medicine, 4(6),
624–630.
[18] Shirani,
F., Teimoori, A., Rashno, M., Latifi, S. M., Karandish, M., 2017, Using rats as
a research model to investigate the effect of human adenovirus 36 on weight gain.
Arya Atherosclerosis, 13(4), 167–171.
[19] Lohrke, J., Frisk, A. L., Frenzel, T.,
Schöckel, L., Rosenbruch, M., Jost, G., Lenhard, D. C., Sieber, M. A., Nischwitz,
V., Küppers, A., Pietsch, H.,2017, Histology and Gadolinium Distribution in the
Rodent Brain After the Administration of Cumulative High Doses of Linear and Macrocyclic
Gadolinium-Based Contrast Agents. Investigative
Radiology, 52(6), 324–333.
https://doi.org/10.1097/RLI.0000000000000344.
[20] Parasuraman,
S., 2011, Toxicological screening. Journal of Pharmacology and Pharmacotherapy,
2(2),74-79. doi: 10.4103/0976-500X.81895
[21] Kanda, T., Osawa, M., Oba, H., Toyoda,
K., Kotoku, J., Haruyama, T., Takeshita, K., & Furui, S. (2015b). High Signal
Intensity in Dentate Nucleus on Unenhanced T1-weighted MR Images: Association with
Linear versus Macrocyclic Gadolinium Chelate Administration. Radiology, 275(3), 803–809. https://doi.org/10.1148/radiol.14140364.
[22] McDonald,
R. J., McDonald, J. S., Kallmes, D. F., Jentoft, M. E., Paolini, M. A., Murray,
D. L., Williamson, E. E., Eckel, L. J., 2017a, Gadolinium Deposition in Human Brain
Tissues after Contrast-enhanced MR Imaging in Adult Patients without Intracranial
Abnormalities. Radiology, 285(2), 546–554. https://doi.org/10.1148/radiol.2017161595.
[23] Murata,
N., Gonzalez-Cuyar, L.F., Murata, K., Fligner, C., Dills, R., Hippe, D., Maravilla,
K.R., 2016, Macrocyclic and other nongroups 1 gadolinium contrast agents deposit
low levels of gadolinium in brain and bone tissue: preliminary results from 9 patients
with normal renal function. Investigative Radiology. doi:10.1097/rli.0000000000000252.
[24] Wáng, Y. X., Schroeder, J., Siegmund, H., Idée, J. M., Fretellier, N., Jestin-Mayer, G., Factor, C., Deng, M., Kang, W., Morcos, S. K., 2015, Total gadolinium tissue deposition and skin structural findings following the administration of structurally different gadolinium chelates in healthy and ovariectomized female rats. Quantitative Imaging in Medicine and Surgery,5(4),534–545. https://doi.org/10.3978/j.issn.2223.4292.2015.05.03.
[25] Gibby, W.A.,
Gibby, K.A., Gibby, W.A., 2004, Comparison
of Gd DTPA-BMA (Omniscan) versus Gd HP-DO3A (ProHance) retention in human bone tissue
by inductively coupled plasma atomic emission 2 eespectroscopy. Investigative Radiology, 39,138–142.