Gadolinium Deposition Disease

Semelka, Richard C.; Ramalho, Miguel

doi:10.1097/rli.0000000000000977

Cited by 20 publications

(3 citation statements)

References 54 publications

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“…Even though nonspecific signs and symptoms have been reported, there is currently no scientific evidence of a causal relationship between GBCA exposure and the occurrence of these various symptoms. The spectrum of symptoms and signs in association with Gd presence reported by a small number of patients includes neurologic, cognitive, musculoskeletal, and other nonspecific complaints, as well as a potential elevation in cytokine levels 57 . The term GDD prematurely presumes a causal relationship between the presence of Gd and the manifestations of multiple symptoms, and is not accepted by the scientific community or medical societies, especially because the methodologic rigor of evidence generation used by its proponents does not support any such conclusion.…”

Section: Results and Assessmentmentioning

confidence: 99%

Clinical Safety of Gadobutrol: Review of Over 25 Years of Use Exceeding 100 Million Administrations

Endrikat,

Gutberlet,

Hoffmann

et al. 2024

Invest Radiol

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Background The macrocyclic gadolinium-based contrast agent gadobutrol was introduced to the market in February 1998. Over the last 25 years, gadobutrol has been administered more than 100 million times worldwide providing a wealth of data related to safety. Objective The aim of this study was to perform a thorough review and status update on gadobutrol's safety. Materials and Methods Safety data from the clinical phase II–IV program and postmarketing surveillance were descriptively analyzed from February 1998 until December 31, 2022. Literature on special at-risk populations and specific safety aspects was critically summarized. Results Forty-five clinical phase II–IV studies recruited 7856 patients receiving gadobutrol. Drug-related adverse events (AEs) were reported in 3.4% and serious AEs in <0.1% of patients. Nausea (0.7%) and dysgeusia (0.4%) were the most reported AEs. All other drug-related AEs occurred ≤0.3%. After more than 100 million gadobutrol administrations, overall adverse drug reactions (ADRs) from postmarketing surveillance (including clinical trials) were rare with an overall reporting rate of 0.0356%, hypersensitivity reactions (0.0147%), nausea (0.0032%), vomiting (0.0025%), and dyspnea (0.0010%). All other ADRs were <0.001%. No trend for higher rates of AEs was found in patients with reduced renal or liver function. Seven clinical studies reported safety findings in 7292 children ≤18 years, thereof 112 newborns/toddlers younger than 2 years. Overall, 61 ADRs (0.84%) were reported, including 3 serious ones. Adverse events in patients ≥65 years of age (“elderly”) were significantly less frequent than in younger patients. A total of 4 reports diagnostic of or consistent with nephrogenic systemic fibrosis have been received. No causal relationship has been established between clinical signs and symptoms and the presence of small amounts of gadolinium in the body in patients with normal renal function after use of gadobutrol. Conclusions More than 100 million administrations worldwide have shown gadobutrol's well-established benefit-risk profile in any approved indication and populations.

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Section: Results and Assessmentmentioning

confidence: 99%

Clinical Safety of Gadobutrol: Review of Over 25 Years of Use Exceeding 100 Million Administrations

Endrikat,

Gutberlet,

Hoffmann

et al. 2024

Invest Radiol

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“…Other NPs may exhibit magnetic or electrical properties affecting their biodistribution and biocompatibility [ 46 ]. For instance, gadolinium-based NPs are routinely used to enhance magnetic resonance imaging but can have associated toxicity in the event of release [ 47 ]. Other issues arise, such as aggregation due to surrounding potentials and difficulty controlling their performance, which may be affected by their magneto-electric properties.…”

Section: Introductionmentioning

confidence: 99%

Improving the Efficacy of Common Cancer Treatments via Targeted Therapeutics towards the Tumour and Its Microenvironment

Cecchi,

Jackson,

Beckham

et al. 2024

Pharmaceutics

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Cancer is defined as the uncontrolled proliferation of heterogeneous cell cultures in the body that develop abnormalities and mutations, leading to their resistance to many forms of treatment. Left untreated, these abnormal cell growths can lead to detrimental and even fatal complications for patients. Radiation therapy is involved in around 50% of cancer treatment workflows; however, it presents significant recurrence rates and normal tissue toxicity, given the inevitable deposition of the dose to the surrounding healthy tissue. Chemotherapy is another treatment modality with excessive normal tissue toxicity that significantly affects patients’ quality of life. To improve the therapeutic efficacy of radiotherapy and chemotherapy, multiple conjunctive modalities have been proposed, which include the targeting of components of the tumour microenvironment inhibiting tumour spread and anti-therapeutic pathways, increasing the oxygen content within the tumour to revert the hypoxic nature of the malignancy, improving the local dose deposition with metal nanoparticles, and the restriction of the cell cycle within radiosensitive phases. The tumour microenvironment is largely responsible for inhibiting nanoparticle capture within the tumour itself and improving resistance to various forms of cancer therapy. In this review, we discuss the current literature surrounding the administration of molecular and nanoparticle therapeutics, their pharmacokinetics, and contrasting mechanisms of action. The review aims to demonstrate the advancements in the field of conjugated nanomaterials and radiotherapeutics targeting, inhibiting, or bypassing the tumour microenvironment to promote further research that can improve treatment outcomes and toxicity rates.

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“…In addition to NSF, another severe immune reaction of the immune-mediated inflammatory disease type has manifested itself. It is referred to as Gd deposition disease and considered a type of Gd toxicity 5,6 …”

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confidence: 99%

Uptake of Gadolinium-Based Contrast Agents by Blood Cells During Contrast-Enhanced MRI Examination

Ruprecht,

Parakkattel,

Hofmann

et al. 2023

Invest Radiol

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Objectives Gadolinium-based contrast agents (GBCAs) are routinely used in magnetic resonance imaging (MRI) examinations. However, there is limited knowledge about the interaction with and distribution of the drug in human cells. This lack of knowledge is surprising, given that the first interaction of the drug occurs with blood cells. Moreover, recent studies reported gadolinium (Gd) deposition within organs, such as the brain. Hence, this study is aiming to determine the uptake of GBCA in blood cells of patients undergoing contrast-enhanced MRI (ce-MRI) examination. Materials and Methods Human blood was exposed to either gadoterate meglumine (Gd-DOTA) or Eu-DOTA in vitro or was collected from patients undergoing ce-MRI with Gd-DOTA. Uptake of contrast agents (CAs) by blood cells was quantified by Gd measurements using single-cell inductively coupled plasma mass spectrometry (SC-ICP-MS) or, to confirm Gd-DOTA uptake, by a complementary method using Eu-DOTA by time-resolved fluorescence spectroscopy, respectively. Results Uptake of Gd-DOTA or Eu-DOTA into white blood cells (WBCs) ex vivo was detectable by SC-ICP-MS and time-resolved fluorescence spectroscopy. The intracellular concentrations were estimated to be in the range of 1–3 μM. However, no CA uptake into erythrocytes was detected with either method. In total, 42 patients between 30 and 84 years old (24 men, 18 women) were enrolled. White blood cells' uptake of Gd was measured by SC-ICP-MS. Isolated WBCs from patients who underwent ce-MRI examination showed substantial Gd uptake; however, the studied patient group showed an inhomogeneous distribution of Gd uptake. Measurements immediately after MRI examination indicated 21–444 attogram/WBC, corresponding to an intracellular Gd concentration in the range from 0.2 to 5.5 μM. Conclusions This study confirms the ex vivo uptake of GBCA by WBCs and provides the first evidence that GBCA is indeed taken up by WBCs in vivo by patients undergoing ce-MRI examination. However, the observed Gd uptake in WBCs does not follow a log-normal distribution commonly observed in the fields of environmental studies, biology, and medicine. Whether cellular uptake of GBCA is linked to the observed deposition of Gd remains unclear. Therefore, studying the interaction between GBCA and human cells may clarify crucial questions about the effects of Gd on patients after MRI examinations.

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Gadolinium Deposition Disease

Cited by 20 publications

References 54 publications

Clinical Safety of Gadobutrol: Review of Over 25 Years of Use Exceeding 100 Million Administrations

Clinical Safety of Gadobutrol: Review of Over 25 Years of Use Exceeding 100 Million Administrations

Improving the Efficacy of Common Cancer Treatments via Targeted Therapeutics towards the Tumour and Its Microenvironment

Uptake of Gadolinium-Based Contrast Agents by Blood Cells During Contrast-Enhanced MRI Examination

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