Gadolinium is a component of the MRI contrast agent Dotarem. Although Dotarem is the least toxic among MRI contrasts used, gadolinium present in Dotarem accumulates for many years in various organs and tissues exerting toxic effects. We showed previously that gadolinium remains in macrophages for at least 7 days after exposure to Dotarem. However, very little is known about the effect of gadolinium retention on the immune cells such as macrophages. We studied the effect of 1-day and 7-day retention of gadolinium on various functions and molecular pathways of macrophages. Gadolinium retention for 7 days decreased macrophage adhesion and motility and dysregulated the expression of adhesion and fibrotic pathway-related proteins such as Notch1 and its ligand Jagged1, adhesion/migration-related proteins PAK1 and Shp1, immune response-related transcription factors Smad3 and TCF19, and chemokines CXCL10 and CXCL13, and dysregulated the mRNA expression of fibrosis-related genes involved in extracellular matrix (ECM) synthesis, such as Col6a1, Fibronectin, MMP9, and MMP12. It also completely (below a level of detection) shut down the transcription of anti-inflammatory M2 macrophage polarization marker the Arg-1. Such changes, if they occur in MRI patients, can be potentially detrimental to the patient\'s immune system and immune response-related processes.

UNASSIGNED: The realization of MRI contrast agents through chemical protocols of functionalization is a strong domain of research. In this work, we developed and formulated a novel hybrid gold nanoparticle system in which a gold salt (HAuCl4) is combined with dotarem, an MRI contrast agent (DOTA) by chelation (Method IN) and stabilized by a lactose-modified chitosan polymer (CTL; Chitlac) to form DOTA IN-CTL AuNPs.
UNASSIGNED: The authors demonstrate the biological efficiency of these nanoparticles in the case of three cell lines: Mia PaCa-2 (human pancreatic cancer cell line), TIB-75 (murine liver cell line) and KKU-M213 (cholangiocarcinoma cell line). DOTA IN-CTL AuNPs are stable under physiological conditions, are nontoxic, and are very efficient as PTT agents. The highlights, such as high stability and preliminary MRI in vitro and in vivo models, may be suitable for diagnosis and therapy.
UNASSIGNED: We proved that DOTA IN-CTL AuNPs have several advantages: i) Biological efficacy on three cell lines: MIA PaCa-2 (human pancreatic cancer cell line), TIB-75 (murine liver cell line) and KKU-M213 (cholangiocarcinoma cell line); ii) high stability, and no-toxicity; iii) high efficiency as a PPT agent. The study conducted on MRI in vitro and in vivo models will be suitable for diagnosis and therapy.

OBJECTIVE: Intravenous administration of gadolinium-based contrast agents (GBCA) in patients with impaired renal function has been of concern to primary care physicians due to the potential worsening of renal dysfunction and nephrogenic systemic fibrosis (NSF). Our objective was to compare the potential change in estimated glomerular filtration rate (eGFR) in patients with known severe renal dysfunction (eGFR <30 ml/min), following Gadoterate meglumine (GM) administration with patients who do not receive contrast.
METHODS: An IRB-approved retrospective analysis of all patients who underwent MRI examination at our institution, for any indication, between January 2016 and September 2020.
METHODS: pre-MRI eGFR <30 ml/min within 24 h of MRI, follow-up eGFR between 48 and 96 h post-MRI, and absence of peritoneal or hemodialysis. The individuals who received GM (492 scans) were identified as cases, and those who did not receive contrast (1101 scans) were identified as controls for our study. Delta-eGFR response was calculated and covariate-adjusted, and propensity score analysis was performed.
RESULTS: No significant eGFR decrease was observed in patients who received GM compared to those who did not receive GM in our study. Also, no relationship between comorbidity, severity and contrast selection was observed.
CONCLUSIONS: The use of Gadolinium contrast in MRI is often of critical importance for determining accurate anatomic relationships, differentiation of benign from malignant lesions, or determination of resolving vs. worsening disease. Though the risk of contrast administration can never be entirely ignored, especially in patients with low eGFR, our study indicates that safe administration of GM can be performed even in patients with severe kidney disease.

Few studies on the safety of gadolinium-based contrast agents have been performed in children with even fewer focusing on children younger than 2 years of age.
To assess the safety of gadoterate meglumine (Dotarem) in patients younger than 2 years of age by evaluating adverse events following contrast administration.
Pediatric patients younger than 2 years of age undergoing magnetic resonance imaging (MRI) with and without contrast were prospectively enrolled and received a weight-based intravenous dose of gadoterate meglumine (0.1 mmol/kg). The occurrence of adverse events was assessed at the time of injection, 2 h after MRI, and by phone contact using a standard questionnaire 24 h after MRI. Adverse events were documented including the time of onset, duration of symptoms, intensity, causality and subsequent outcome. Descriptive statistics were used to characterize patient information.
One hundred fifty exams were completed in 150 patients (median age: 12.1 months, age range: 0.25-23 months; males: 56%). Almost all patients (97.3%) received sedation/anesthesia before and during MRI. Thirty-four adverse events were reported in 23 patients overall (15.3%; male: 73.9%; median age: 11 months, age range: 3-23 months). Within the initial 2 h after the injection, there was one report of transient flushing/warmth and one report of vomiting, the latter of which was related to drinking formula too soon after anesthesia. Twenty-two patients (14.7%), who had all received sedation/anesthesia, experienced minor adverse events within 24 h, most physiological. Fourteen patients (9.3%) reported emesis, eight (5.3%) reported transient flushing/warmth, seven (4.7%) reported nausea, one (0.7%) reported altered taste and one (0.7%) reported dizziness. No patient experienced anaphylaxis. Two patients (1.3%) reported allergic-like reactions, which consisted of wheezing or sneezing.
No patient experienced adverse events directly related to gadoterate meglumine. Only two adverse events were reported to have occurred in the initial 2 h after the exam, while the rest were reported on the 24-h follow-up call. The higher reported rate of adverse events in this study may be related to concomitant sedation/anesthesia as well as to overreporting from parents on the 24-h follow-up questionnaire. The study confirms a good safety profile for gadoterate meglumine in this very sensitive population.

Epac1-/- mice, but not Epac2-/- mice have elevated baseline permeability to albumin. This study extends the investigations of how Epac-dependent pathways modulate transvascular exchange in response to the classical inflammatory agent histamine. It also evaluates the limitations of models of blood-to-tissue exchange in transgenic mice in DCE-MRI measurements.
We measured DCE-MRI signal intensity in masseter muscle of wt and Epac1-/- mice with established approaches from capillary physiology to determine how changes in blood flow and vascular permeability contribute to overall changes of microvascular flux. We used two tracers, the high molecular weight tracer (Gadomer-17, MW 17 kDa, apparent MW 30-35 kDa) is expected to be primarily limited by diffusion and therefore less dependent on changes in blood flow and the low molecular weight tracer (Dotarem (MW 0.56 kDa) whose transvascular exchange is determined by both blood flow and permeability. Paired experiments in each animal combined with analytical methods provided an internally consistent description of microvascular transport.
Epac1-/- mice had elevated baseline permeability relative to wt control mice for Dotarem and Gadomer-17. In contrast to wt mice, Epac1-/- mice failed to increase transvascular permeability in response to histamine. Dotarem underestimated blood flow and vascular volume and Gadomer-17 has limited sensitivity in extravascular accumulation.
The study suggests that the normal barrier loosening effect of histamine in venular microvessels do not function when the normal barrier tightening effect of Epac1 is already compromised. The study also demonstrated that the numerical analysis of DCE-MRI data with tracers of different molecular weight has significant limitations.

OBJECTIVE: To examine the risks of using of gadolinium-based contrast agents (GBCAs) in magnetic resonance (MR) imaging and explore strategies to reduce the likeliness of adverse effects in patients who might be at risk for developing nephrogenic system fibrosis (NSF).
METHODS: A search of 3 scholarly databases was performed to identify articles that discuss adverse reactions to GBCAs, specifically relating to kidney function, in MR examinations. A total of 20 peer-reviewed articles were analyzed.
CONCLUSIONS: Safety of contrast media is related to the stability of the chelate bond (ie, macrocyclic or linear). Patients who have decreased kidney function or chronic kidney disease are at higher risk for an adverse reaction to GBCAs; typically, macrocyclic contrast agents are considered safer than linear contrast agents for patients at risk for developing NSF because of their higher kinetic stability. Recommended doses of gadolinium should be adhered to carefully for all patients in conjunction with the glomerular filtration rate guidelines for contrast administration defined by the American College of Radiology.
CONCLUSIONS: Although there are advantages to contrast use in MR examinations, technologists should work closely with referring physicians and radiologists to minimize risks for developing NSF in patients who have decreased kidney function.