CEST-MRI is an emerging imaging technique suitable for various in vivo applications, including the quantification of tumor acidosis. Traditionally, CEST contrast is calculated by asymmetry analysis, but the presence of fat signals leads to wrong contrast quantification and hence to inaccurate pH measurements. In this study, we investigated four post-processing approaches to overcome fat signal influences and enable correct CEST contrast calculations and tumor pH measurements using iopamidol. The proposed methods involve replacing the Z-spectrum region affected by fat peaks by (i) using a linear interpolation of the fat frequencies, (ii) applying water pool Lorentzian fitting, (iii) considering only the positive part of the Z-spectrum, or (iv) calculating a correction factor for the ratiometric value. In vitro and in vivo studies demonstrated the possibility of using these approaches to calculate CEST contrast and then to measure tumor pH, even in the presence of moderate to high fat fraction values. However, only the method based on the water pool Lorentzian fitting produced highly accurate results in terms of pH measurement in tumor-bearing mice with low and high fat contents.

BACKGROUND: Two-dimensional (2D) classifications of iodinated contrast media (ICM) are insufficient to explain the observed skin test (ST) reactivity patterns in patients with drug hypersensitivity reactions (DHRs) to ICM.
OBJECTIVE: To refine the current view on allergic DHRs to ICM by analyzing ST reactivity patterns in patients with previous reactions to ICM.
METHODS: Patients with a history of DHR to ICM and positive STs, who presented at the University Hospital of Montpellier between 2004 and 2022, were included in the study. The relative difference between every two ICM products was measured by Manhattan distance and odds ratios were computed for all pairs of products in the immediate reaction (IR) and non-immediate reaction (NIR) ST groups.
RESULTS: A total of 181 patients were included in the study. Odds ratio analysis identified significant associations between classical cross-reactive ICM, such as iohexol-ioversol, iohexol-iomeprol, iomeprol-ioversol, and iohexol-iodixanol in the IR ST group and iohexol-ioversol, iopromide-iohexol, and iomeprol-ioversol in the NIR ST group. We also identified uncommon associations, such as ioxitalamate-amidotrizoate in the IR ST group and amidotrizoate-iopamidol and amidotrizoate-ioxitalamate in the NIR ST group. The results were reflected by the Manhattan distance, which suggested the existence of clusters containing the same classically associated ICM as well as uncommon associations, which we hypothesize to be related to similarities in the 3D structure of the respective ICM.
CONCLUSIONS: Current chemical (2D) classifications cannot explain all observed ST reactivity patterns. Whether the 3D structure can be integrated into the current classifications to interpret the observed ST reactivity patterns and predict tolerance to alternative ICM requires further research.

OBJECTIVE: This study aimed to evaluate the Pharmacovigilance (PV) and severity of hypersensitivity reactions induced by non-ionic Iodinated Contrast Media (ICM) in the radiology diagnosis reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS).
METHODS: We retrospectively reviewed the reports of ICM-induced hypersensitivity reactions submitted to the FAERS database between January 2015 and January 2023 and conducted a disproportionality analysis. The seven most common non-ionic ICM, including iohexol, iopamidol, ioversol, iopromide, iomeprol, iobitridol, and iodixanol, were chiefly analyzed. Our primary endpoint was the PV of non-ionic ICM-induced total hypersensitivity events. STATA 17.0 MP was used for statistical analysis.
RESULTS: In total, 35357 reports of adverse reaction events in radiology diagnosis were retrieved from the FAERS database. Among them, 6181 reports were on hypersensitivity reaction events (mean age: 57.1 ± 17.8 years). The hypersensitivity reaction-related PV signal was detected for iohexol, ioversol, iopromide, iomeprol, iobitridol, and iodixanol, but not for iopamidol. The proportion of iomeprol-induced hypersensitivity reactions and the probability of ioversol-induced severe hypersensitivity reactions have been found to be significantly increased.
CONCLUSIONS: The probability and severity of hypersensitivity reaction events in non-ionic ICM are different. Iohexol, ioversol, iopromide, iomeprol, iobitridol, and iodixanol have higher risks compared to iopamidol. In addition, the constituent ratio of hypersensitivity reactions induced by iomeprol is significantly increased, and the associated probability induced by ioversol is significantly increased.

OBJECTIVE: This multicenter prospective study aimed to evaluate the quality and diagnostic effectiveness of cerebral angiography images obtained using low-concentration iodinated contrast agents (iohexol 240 mgI/mL, iopamidol 250 mgI/mL, and iodixanol 270 mgI/mL) and to assess the safety thereof. The study addresses the need for safer contrast agent alternatives without compromising the diagnostic quality of identifying cerebrovascular disease.
METHODS: Conducted in 5 medical centers in South Korea, we enrolled patients aged 19 years or older who were referred for diagnostic cerebral angiography under non-emergency conditions, excluding those with specific health conditions and sensitivities. The study design included a prospective, observational approach with a 1-way analysis of variance (ANOVA) for sample size calculation, aiming for a total sample of 231 participants for adequate power. Image quality was evaluated using a 4-level scale by 2 independent, blinded radiologists, and adverse reactions were monitored both immediately and up to 7 days post-procedure. Statistical analysis involved 1-way ANOVA and Kruskal-Wallis tests to assess the image quality and safety profiles of the contrast agents.
RESULTS: Among 266 patients screened, 243 were included in the final analysis. The evaluation revealed no statistically significant differences in image quality among the 3 types of low-concentration contrast agents. Adverse events were observed in 28.8% of patients, with 27.2% experiencing acute reactions, primarily mild reactions, and 3.3% experiencing delayed reactions. The overall safety profile showed no significant changes in vital signs or electrocardiogram readings before and after contrast agent injection.
CONCLUSIONS: Using low-concentration iodinated contrast agents for cerebral angiography provides image quality comparable to that of conventional high-concentration agents, with no significant increase in adverse events, suggesting a safer alternative for patients.

BACKGROUND: Exposure of iodinated contrast media (ICM) to X-rays is not uncommon, as contrast media are often stored in close proximity to radiological equipment. However, the interaction between X-rays and ICM is not widely investigated in literature. The present study aims to investigate the chemical stability of iomeprol and iopamidol, two commercial iodinated ICM commonly used in diagnostic imaging, under X-rays exposure.
METHODS: Different formulations of iopamidol and iomeprol (iodine concentration 9 to 400 mgI/mL, volume 50-500 mL) were exposed to three different conditions of X-ray irradiation: i) 1 month storage in CT room (≈5-15 mGy); (ii) low-dose protocol (≈10 mGy); (ii) stressed protocol (≈100 mGy). Unexposed and exposed solutions were characterized by high-performance liquid chromatography in terms of concentration of active pharmaceutical ingredient (API), iodine species and by products. In addition, appearance and colour of the solutions were inspected and pH measured.
RESULTS: API concentrations, appearance, colour and pH of the exposed formulations remained unaffected by X-rays. Measured concentrations of iodine species and by products were observed well within the acceptability criteria, i.e. values turned out to be lower than specifications limits established by the manufacturer, considering both release and shelf-life values.
CONCLUSIONS: Up to 100 mGy X-ray exposure did not induce any alteration of iomeprol and iopamidol formulation, nor a detectable increase in the concentration of iodine species or by-products.
CONCLUSIONS: Our study strengthens the hypothesis that ICM are stable under X-rays exposure up to 100 mGy.

BACKGROUND: Iopamidol is a non-ionic, water-soluble iodine contrast agent that is considered safe for intravenous or intra-arterial administration and is widely used both in the general population and in patients undergoing oncological treatment. While adverse reactions to iopamidol have been documented, to date, no pulmonary and gastric hemorrhages induced by iopamidol have been reported in oncology patients. We report the first case of this complication.
METHODS: We report the case of a 60-year-old woman with marginal zone lymphoma who was receiving antineoplastic therapy. As part of the investigation for the condition, she underwent chest enhancement CT with iopamidol. Shortly thereafter(within five minutes), she experienced hemoptysis and hematemesis. She was intubated and admitted to the intensive care unit. Pre- and post-contrast images demonstrated the course of the hemorrhage. Flexible bronchoscopy and gastroscopy on the following day showed no active bleeding, and the patient recovered completely after antiallergy treatment. We speculate that contrast-induced hypersensitivity was the most likely cause of the transient pulmonary and gastric bleeding.
CONCLUSIONS: Although rare, the complications of iopamidol, which may cause allergic reactions in the lungs and stomach, should be considered.

A multi-residue UHPLC-MS/MS analytical method, previously developed for monitoring 52 pharmaceuticals in drinking water, was used to analyse these pharmaceuticals in wastewater originating from healthcare facilities in the Czech Republic. Furthermore, the methodology was expanded to include the evaluation of the effectiveness of drug removal in Czech wastewater treatment plants (WWTPs). Of the 18 wastewater samples analysed by the validated UHPLC-MS/MS, each sample contained at least one quantifiable analyte. This study reveals the prevalence of several different drugs; mean concentrations of 702 μg L-1 of iomeprol, 48.8 μg L-1 of iopromide, 29.9 μg L-1 of gabapentin, 42.0 μg L-1 of caffeine and 82.5 μg L-1 of paracetamol were present. An analysis of 20 samples from ten WWTPs revealed different removal efficiencies for different analytes. Paracetamol was present in the inflow samples of all ten WWTPs and its removal efficiency was 100%. Analytes such as caffeine, ketoprofen, naproxen or atenolol showed high removal efficiencies exceeding 80%. On the other hand, pharmaceuticals like furosemide, metoprolol, iomeprol, zolpidem and tramadol showed lower removal efficiencies. Four pharmaceuticals exhibited higher concentrations in WWTP effluents than in the influents, resulting in negative removal efficiencies: warfarin at -9.5%, indomethacin at -53%, trimethoprim at -54% and metronidazole at -110%. These comprehensive findings contribute valuable insights to the pharmaceutical landscape of wastewater from healthcare facilities and the varied removal efficiencies of Czech WWTPs, which together with the already published literature, gives a more complete picture of the burden on the aquatic environment.

5-Aminoisophthalic acid and 5-nitroisophthalic acid (5-NIPA) are potential impurities in preparations of 5-amino-2,4,6-triiodoisophthalic acid, which is a key intermediate in the synthesis of the iodinated contrast agent iopamidol. We have studied their mutagenicity in silico (quantitative structure-activity relationships, QSAR) and by the bacterial reverse mutation assay (Ames test). First, the compounds were screened with the tools Derek Nexus™ and Leadscope®. Both compounds were flagged as potentially mutagenic (class 3 under ICH M7). However, contrary to the in silico prediction, neither chemical was mutagenic in the Ames test (plate incorporation method) with or without S9 metabolic activation.

NaHCO3-activated buckwheat biochar was studied, and an optimal biochar of 0.25N-BC [m(NaHCO3):m(buckwheat bark)=0.25:1]was selected. SEM, BET, XRD, Raman, FTIR, and XPS methods were applied to analyze the effects of NaHCO3 on the physicochemical properties of buckwheat biochar. The adsorption properties and mechanism of NaHCO3-activated buckwheat biochar for iopamidol(IPM), a nonionic iodol X-ray contrast agent, were also investigated. The results showed that compared with buckwheat skin biochar(BC), NaHCO3-activated biochar had higher structural defects(surface area and pore volume increased, respectively, from 480.40 m2·g-1 and 0.29 cm3·g-1 to 572.83 m2·g-1 and 0.40 cm3·g-1, with ID/IG being 1.22 times that of BC), the carbon and oxygen functional groups on the BC surface changed significantly, and the polarity increased [(N+O)/C from 0.15 to 0.24]. The maximum adsorption capacity of 0.25N-BC for IPM was 74.94 mg·g-1, which was 9.51 times that of BC(7.88 mg·g-1). The pseudo-second-order adsorption kinetics and Langmuir and Freundlich isotherm models could well fit the adsorption of 0.25N-BC for IPM. The adsorption processes were mainly chemical, monolayer, and heterogeneous multilayer adsorption. Pore filling, hydrogen bonding, π-π, and n-π interactions were the main mechanisms of 0.25N-BC adsorption for IPM. Comparing the activated buckwheat biochar by different bases [KOH, Na2CO3, NaHCO3, KHCO3, and Ca(HCO3)2], 0.25N-BC exhibited high adsorption capability and short equilibrium time and could effectively remove the IPM residue in the actual water(secondary sedimentation tank effluent and lake). The removal rate of IPM remained at 74.91% after three adsorption-desorption cycles. The results showed that NaHCO3-activated buckwheat biochar was a green, effective, and sustainable adsorbent for the removal of iodine-containing organic matter.

OBJECTIVE: To compare 2 ratios of n-butyl-2-cyanoacrylate (nBCA)-ethiodized oil (Lipiodol)-iopamidol (NLI) in balloon-assisted portal vein embolization (PVE) in swine.
METHODS: In an in vitro study, NLI prepared at a ratio of 2:3:1 (NLI231) or 1:4:1 (NLI141) was injected into 2.5- or 10-mL syringes filled with swine blood, and the viscosity of NLI was measured to determine an appropriate balloon occlusion time. Two portal vein branches in 8 female swine (n = 16 vein branches) were embolized with NLI231 (n = 8) or NLI141 (n = 8) under balloon occlusion. Portal venography was performed before, immediately after, and 3 days after PVE to evaluate the migration of NLI and the recanalization of embolized portal vein branches. Then, the livers were removed for histopathologic evaluation.
RESULTS: The times to peak viscosity of NLI231 in the 2.5- and 10-mL syringes were 55.8 seconds (SD ± 7.0) and 85.2 seconds (SD ± 6.3), and those to peak viscosity of NLI141 were 129.2 seconds (SD ± 11.8) and 254.0 seconds (SD ± 21.8), respectively. No migration of NLI231 was observed in all 8 procedures immediately or 3 days after PVE. Migration of NLI141 was observed in 6 of 8 procedures within 3 days after PVE. The migration frequency of the embolic material was lower in the NI231 group than in the NLI141 group (0/8 vs 6/8; P = .051). Histologically, NLI231 occupied the portal veins without any thrombi, whereas NLI141 was accompanied by thrombi in the portal veins.
CONCLUSIONS: NLI231 may be more suitable than NLI141 for balloon-assisted PVE in swine.