Evaluating the potential of chelation therapy to prevent and treat gadolinium deposition from MRI contrast agents

Rees, Julian A.; Deblonde, Gauthier J. -P.; An, Dahlia D.; Ansoborlo, Camille; Gauny, Stacey S.; Abergel, Rebecca J.

doi:10.1038/s41598-018-22511-6

Title: Evaluating the potential of chelation therapy to prevent and treat gadolinium deposition from MRI contrast agents

Journal Article · Tue Mar 13 00:00:00 EDT 2018 · Scientific Reports

DOI:https://doi.org/10.1038/s41598-018-22511-6· OSTI ID:1433132

Rees, Julian A. ^[1]; Deblonde, Gauthier J. -P. ^[1];

^[1]; Ansoborlo, Camille ^[1]; Gauny, Stacey S. ^[1]; Abergel, Rebecca J. ^[2]

Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Chemical Sciences Division
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Chemical Sciences Division; Univ. of California, Berkeley, CA (United States). Dept. of Nuclear Engineering

Several MRI contrast agent clinical formulations are now known to leave deposits of the heavy metal gadolinium in the brain, bones, and other organs of patients. This persistent biological accumulation of gadolinium has been recently recognized as a deleterious outcome in patients administered Gd-based contrast agents (GBCAs) for MRI, prompting the European Medicines Agency to recommend discontinuing the use of over half of the GBCAs currently approved for clinical applications. Here, to address this problem, we find that the orally-available metal decorporation agent 3,4,3-LI(1,2-HOPO) demonstrates superior efficacy at chelating and removing Gd from the body compared to diethylenetriaminepentaacetic acid, a ligand commonly used in the United States in the GBCA Gadopentetate (Magnevist). Using the radiotracer ¹⁵³Gd to obtain precise biodistribution data, the results herein, supported by speciation simulations, suggest that the prophylactic or post-hoc therapeutic use of 3,4,3-LI(1,2-HOPO) may provide a means to mitigate Gd retention in patients requiring contrast-enhanced MRI.

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Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1433132

Journal Information:: Scientific Reports, Vol. 8, Issue 1; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 36 works

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References (29)

Dose-Dependent Efficacy and Safety Toxicology of Hydroxypyridinonate Actinide Decorporation Agents in Rodents: Towards a Safe and Effective Human Dosing Regimen Bunin, Deborah I.; Chang, Polly Y.; Doppalapudi, Rupa S. Radiation Research, Vol. 179, Issue 2 https://doi.org/10.1667/RR3115.1	journal	February 2013
Multiorgan gadolinium (Gd) deposition and fibrosis in a patient with nephrogenic systemic fibrosis--an autopsy-based review Sanyal, S.; Marckmann, P.; Scherer, S. Nephrology Dialysis Transplantation, Vol. 26, Issue 11 https://doi.org/10.1093/ndt/gfr085	journal	March 2011
Stability of Gadolinium-Based Magnetic Resonance Imaging Contrast Agents in Human Serum at 37°C Frenzel, Thomas; Lengsfeld, Philipp; Schirmer, Heiko Investigative Radiology, Vol. 43, Issue 12 https://doi.org/10.1097/RLI.0b013e3181852171	journal	January 2008
Multidentate hydroxypyridinonate ligands for Pu(IV) chelation in vivo : comparative efficacy and toxicity in mouse of ligands containing 1,2-HOPO or Me-3,2-HOPO W. Durbin, B. Kullgren, J. Xu, K. N., P. International Journal of Radiation Biology, Vol. 76, Issue 2 https://doi.org/10.1080/095530000138853	journal	January 2000
A kinetic investigation of the lanthanide DOTA chelates. Stability and rates of formation and of dissociation of a macrocyclic gadolinium(III) polyaza polycarboxylic MRI contrast agent Wang, Xiangyun; Jin, Tianzhu; Comblin, Vinciane Inorganic Chemistry, Vol. 31, Issue 6 https://doi.org/10.1021/ic00032a034	journal	March 1992
In Vivo Chelation of Am(III), Pu(IV), Np(V), and U(VI) in Mice by TREN-(Me-3,2-HOPO) Durbin, P. W.; Kullgren, B.; Xu, J. Radiation Protection Dosimetry, Vol. 53, Issue 1-4 https://doi.org/10.1093/rpd/53.1-4.305	journal	May 1994
Primer on gadolinium chemistry Sherry, A. Dean; Caravan, Peter; Lenkinski, Robert E. Journal of Magnetic Resonance Imaging, Vol. 30, Issue 6 https://doi.org/10.1002/jmri.21966	journal	December 2009
Biodistribution of the Multidentate Hydroxypyridinonate Ligand [ ¹⁴ C]-3,4,3-LI(1,2-HOPO), a Potent Actinide Decorporation Agent : BIODISTRIBUTION OF 3,4,3-LI(1,2-HOPO) Choi, Taylor A.; Endsley, Aaron N.; Bunin, Deborah I. Drug Development Research, Vol. 76, Issue 3 https://doi.org/10.1002/ddr.21246	journal	April 2015
Biomimetic Actinide Chelators: an Update on the Preclinical Development of the Orally Active Hydroxypyridonate Decorporation Agents 3,4,3-Li(1,2-Hopo) and 5-Lio(Me-3,2-Hopo) Abergel, Rebecca J.; Durbin, Patricia W.; Kullgren, Birgitta Health Physics, Vol. 99, Issue 3 https://doi.org/10.1097/HP.0b013e3181c21273	journal	January 2010
Gadolinium Retention in the Dentate Nucleus and Globus Pallidus Is Dependent on the Class of Contrast Agent Radbruch, Alexander; Weberling, Lukas D.; Kieslich, Pascal J. Radiology, Vol. 275, Issue 3 https://doi.org/10.1148/radiol.2015150337	journal	June 2015
Gadolinium released from MR contrast agents is deposited in brain tumors: in situ demonstration using scanning electron microscopy with energy dispersive X-ray spectroscopy Xia, Daniel; Davis, Richard L.; Crawford, Judith A. Acta Radiologica, Vol. 51, Issue 10 https://doi.org/10.3109/02841851.2010.515614	journal	December 2010
3,4,3-LI(1,2-HOPO): In vitro formation of highly stable lanthanide complexes translates into efficacious in vivo europium decorporation Sturzbecher-Hoehne, Manuel; Ng Pak Leung, Clara; D'Aléo, Anthony Dalton Transactions, Vol. 40, Issue 33 https://doi.org/10.1039/c1dt10840a	journal	January 2011
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 Kanda, Tomonori; Fukusato, Toshio; Matsuda, Megumi Radiology, Vol. 276, Issue 1 https://doi.org/10.1148/radiol.2015142690	journal	July 2015
Using the Antenna Effect as a Spectroscopic Tool: Photophysics and Solution Thermodynamics of the Model Luminescent Hydroxypyridonate Complex [Eu ^III (3,4,3-LI(1,2-HOPO))] ⁻ Abergel, Rebecca J.; D’Aléo, Anthony; Ng Pak Leung, Clara Inorganic Chemistry, Vol. 48, Issue 23 https://doi.org/10.1021/ic9013703	journal	December 2009
Gadolinium toxicity: Iron and ferroportin as central targets Swaminathan, Sundararaman Magnetic Resonance Imaging, Vol. 34, Issue 10 https://doi.org/10.1016/j.mri.2016.08.016	journal	December 2016
²³⁸ Pu elimination profiles after delayed treatment with 3,4,3LI(1,2HOPO) in female and male Swiss-Webster mice An, Dahlia D.; Villalobos, Jonathan A.; Morales-Rivera, Joel A. International Journal of Radiation Biology, Vol. 90, Issue 11 https://doi.org/10.3109/09553002.2014.925150	journal	August 2014
Gross Composition and Plasma and Extracellular Water Volumes of Tissues of a Reference Mouse Durbin, P. W.; Jeung, N.; Kullgren, B. Health Physics, Vol. 63, Issue 4 https://doi.org/10.1097/00004032-199210000-00007	journal	January 1992
Gadodiamide-Associated Nephrogenic Systemic Fibrosis: Why Radiologists Should Be Concerned Broome, Dale R.; Girguis, Mark S.; Baron, Pedro W. American Journal of Roentgenology, Vol. 188, Issue 2 https://doi.org/10.2214/AJR.06.1094	journal	February 2007
Gadolinium based contrast agents (GBCA): Safety overview after 3 decades of clinical experience Kanal, Emanuel Magnetic Resonance Imaging, Vol. 34, Issue 10 https://doi.org/10.1016/j.mri.2016.08.017	journal	December 2016
Gadolinium deposition in the brain: Lessons learned from other metals known to cross the blood–brain barrier Prybylski, John P.; Maxwell, Erin; Coste Sanchez, Carla Magnetic Resonance Imaging, Vol. 34, Issue 10 https://doi.org/10.1016/j.mri.2016.08.018	journal	December 2016
Comparison of Gd(DTPA-BMA) (Omniscan) Versus Gd(HP-DO3A) (ProHance) Relative to Gadolinium Retention in Human Bone Tissue by Inductively Coupled Plasma Mass Spectroscopy White, Gregory W.; Gibby, Wendell A.; Tweedle, Michael F. Investigative Radiology, Vol. 41, Issue 3 https://doi.org/10.1097/01.rli.0000186569.32408.95	journal	January 2006
Receptor recognition of transferrin bound to lanthanides and actinides: a discriminating step in cellular acquisition of f-block metals Deblonde, Gauthier J. -P.; Sturzbecher-Hoehne, Manuel; Mason, Anne B. Metallomics, Vol. 5, Issue 6 https://doi.org/10.1039/c3mt20237b	journal	January 2013
From early prophylaxis to delayed treatment: Establishing the plutonium decorporation activity window of hydroxypyridinonate chelating agents An, Dahlia D.; Kullgren, Birgitta; Jarvis, Erin E. Chemico-Biological Interactions, Vol. 267 https://doi.org/10.1016/j.cbi.2016.03.034	journal	April 2017
Gadolinium-based contrast agent toxicity: a review of known and proposed mechanisms Rogosnitzky, Moshe; Branch, Stacy BioMetals, Vol. 29, Issue 3 https://doi.org/10.1007/s10534-016-9931-7	journal	April 2016
In Vivo Chelation of Am(III), Pu(IV), Np(V), and U(VI) in Mice by TREN-(Me-3,2-HOPO) Durbin, P. W.; Kullgren, B.; Xu, J. Radiation Protection Dosimetry, Vol. 53, Issue 1-4 https://doi.org/10.1093/oxfordjournals.rpd.a082298	journal	May 1994
Specific sequestering agents for the actinides. 16. Synthesis and initial biological testing of polydentate oxohydroxypyridinecarboxylate ligands White, David L.; Durbin, Patricia W.; Jeung, Nylan Journal of Medicinal Chemistry, Vol. 31, Issue 1, p. 11-18 https://doi.org/10.1021/jm00396a005	journal	January 1988
Lauriston s. Taylor Lecture: the Quest for Therapeutic Actinide Chelators Durbin, Patricia W. Health Physics, Vol. 95, Issue 5 https://doi.org/10.1097/01.hp.0000326345.41816.c2	journal	January 2008
Revisiting the Pharmacokinetic Profiles of Gadolinium-Based Contrast Agents: Differences in Long-Term Biodistribution and Excretion Lancelot, Eric Investigative Radiology, Vol. 51, Issue 11 https://doi.org/10.1097/rli.0000000000000280	journal	January 2016
Nephrogenic Systemic Fibrosis: Suspected Causative Role of Gadodiamide Used for Contrast-Enhanced Magnetic Resonance Imaging Marckmann, Peter; Skov, Lone; Rossen, Kristian Journal of the American Society of Nephrology, Vol. 17, Issue 9 https://doi.org/10.1681/asn.2006060601	journal	August 2006

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High-throughput screening for discovery of benchtop separations systems for selected rare earth elements Nelson, Joshua J. M.; Cheisson, Thibault; Rugh, Haley J. Communications Chemistry, Vol. 3, Issue 1 https://doi.org/10.1038/s42004-019-0253-x	journal	January 2020
Lanthanum chloride induces autophagy in rat hippocampus through ROS-mediated JNK and AKT/mTOR signaling pathways Gao, Xiang; Yang, Jinghua; Li, Yingqi Metallomics, Vol. 11, Issue 2 https://doi.org/10.1039/c8mt00295a	journal	January 2019
Inducing selectivity and chirality in group IV metal coordination with high-denticity hydroxypyridinones Deblonde, Gauthier J. -P.; Lohrey, Trevor D.; Abergel, Rebecca J. Dalton Transactions, Vol. 48, Issue 23 https://doi.org/10.1039/c9dt01031a	journal	January 2019
Combinatorial design of multimeric chelating peptoids for selective metal coordination Ricano, Abel; Captain, Ilya; Carter, Korey P. Chemical Science, Vol. 10, Issue 28 https://doi.org/10.1039/c9sc01068h	journal	January 2019
Gadolinium-based contrast agents – what is the evidence for ‘gadolinium deposition disease’ and the use of chelation therapy? Layne, Kerry A.; Wood, David M.; Dargan, Paul I. Clinical Toxicology, Vol. 58, Issue 3 https://doi.org/10.1080/15563650.2019.1681442	journal	October 2019
Ex vivo quantification of lanthanum and gadolinium in post-mortem human tibiae with estimated barium and iodine concentrations using K x-ray fluorescence Nguyen, Joanna; Crawford, Daniel; Howarth, David Physiological Measurement, Vol. 40, Issue 8 https://doi.org/10.1088/1361-6579/ab3c0e	journal	August 2019
Fibromyalgia associated with repeated gadolinium contrast-enhanced MRI examinations Lattanzio, Silvia Maria; Imbesi, Francesca Radiology Case Reports, Vol. 15, Issue 5 https://doi.org/10.1016/j.radcr.2020.02.002	journal	May 2020
Removal of a gadolinium based contrast agent by a novel sorbent hemoperfusion in a chronic kidney disease (CKD) rodent model Ngamcherdtrakul, Worapol; Morry, Jingga; Sangvanich, Thanapon Scientific Reports, Vol. 9, Issue 1 https://doi.org/10.1038/s41598-018-37348-2	journal	January 2019
Impact of Treatment With Chelating Agents Depends on the Stability of Administered GBCAs Boyken, Janina; Frenzel, Thomas; Lohrke, Jessica Investigative Radiology, Vol. 54, Issue 2 https://doi.org/10.1097/rli.0000000000000522	journal	February 2019
Recent Advances of Bioresponsive Nano-Sized Contrast Agents for Ultra-High-Field Magnetic Resonance Imaging Hu, Hailong Frontiers in Chemistry, Vol. 8 https://doi.org/10.3389/fchem.2020.00203	journal	March 2020

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