Measuring the density of iodine depositions: Detecting an invisible residual tumor after conventional transarterial chemoembolization.

PURPOSE: The purpose of this study is to evaluate the use of density measurements in the diagnosis of an underlying residual tumor beyond iodine depositions after Lipiodol-based conventional transarterial chemoembolization (cTACE). METHOD AND MATERIALS: Thirty follow-up CT scans of 20 patients 6-12 weeks after Lipiodol-based cTACE, receiving a digital subtraction angiography at the same time, were analyzed. Reference for the detection of a residual tumor was the angiography, and a visible contrast enhancement was categorized as a residual tumor (n = 16 with residual tumor; n = 14 without residual tumor). The density of the iodine depositions was measured in all containing slices in non-contrast-, arterial- and portal venous-phase CT scans, with a slice thickness of 5.00 mm. The mean density of the iodine deposition during the portal venous phase was subtracted from the mean density of the arterial phase to calculate the density changes (a positive enhancement score represents washout in the portal venous phase). In addition, a quotient relating to the non-contrast measurement was evaluated. RESULTS: Patients with a residual tumor displayed significantly higher enhancement scores in favor of density reduction between the arterial and portal venous phases, compared to patients without a residual tumor (1.41 ± 3.59, n = 14 vs. -13.97 ± 2.88, n = 16; p-value < 0.01). Furthermore, 87.75% of patients with an enhancement score higher than -1.00 (n = 9) had a residual tumor, whereas 100.00% of patients with an enhancement score lower than -20.00 (n = 6) were shown to be tumor-free. The enhancement score quotient resulted in similar findings. CONCLUSION: After cTACE in patients with hepatocellular carcinoma (HCC), the presence of a viable tumor correlated with enhancement scores based on the density measurements of iodine depositions in different phases of the CT scan. Low enhancement scores were associated with completely treated tumors and can aid the decision process to avoid possibly unnecessary angiographies.

Removal of a gadolinium based contrast agent by a novel sorbent hemoperfusion in a chronic kidney disease (CKD) rodent model.

Gadolinium based contrast agents (GBCAs) have been linked to toxicity in patients, regardless of having impaired or normal renal function. Currently, no therapy is considered highly effective for removing gadolinium (Gd) from the body. We propose a new strategy to reduce blood Gd content that facilitates whole body removal of Gd using a hemoperfusion system consisting of a cartridge of porous silica beads (Davisil®) functionalized with 1,2-hydroxypyridinone (1,2-HOPO). Herein, we report optimization of the hemoperfusion system using an ex vivo blood and an in vivo rat model of chronic kidney disease (CKD). In our ex vivo system, 1,2-HOPO-Davisil outperformed Gambro activated charcoal (AC), which is commonly used in clinical hemoperfusion of aqueous toxins, in terms of Gd capture capacity and rate. In the CKD rat model, the 1,2-HOPO-Davisil hemoperfusion system removed Gd by 3.4 times over the Gambro AC system. 1,2-HOPO-Davisil did not change complete blood counts and common blood biochemistry. Thus, this strategy has great potential for clinical translation to manage GBCAs after magnetic resonance imaging (MRI), before Gd can deposit in the body and cause long-term toxicity. Although gadodiamide was used as a proof of concept model for GBCAs in this study, 1,2-HOPO functionalized mesoporous silica could also capture dissociated Gd and other GBCAs.

Different sample treatments for the determination of ICM-XR in fish samples followed by LC-HRMS.

Iodinated X-ray contrast media (ICM-XR) are a group of pharmaceuticals widely used in medicine. Due to their low biodegradation rate, which makes their removal at wastewater treatment plants difficult, and the high doses at which they are administered, they have been detected in aquatic environments. In the present paper, a method for the quantitative determination of a group of ICM-XR in different fish species was developed and validated for the first time. Two extraction techniques were compared: pressurised liquid extraction (PLE) and QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe), with PLE being selected, followed by liquid chromatography-high resolution mass spectrometry. In addition, several clean-up strategies were evaluated. The optimised method provided PLE recoveries ranging from 60% to 88% and limits of detection ranging from 5ng/g to 25ng/g (dry weight). The method was applied in order to evaluate the presence of the selected ICM-XR in different fish species.

Gadolinium-uptake by aquatic and terrestrial organisms-distribution determined by laser ablation inductively coupled plasma mass spectrometry.

Gadolinium (Gd) based contrast agents (CA) are used to enhance magnetic resonance imaging. As a consequence of excretion by patients and insufficient elimination in wastewater treatment plants they are detected in high concentrations in surface water. At present, little is known about the uptake of these species by living organisms in aquatic systems. Therefore the uptake of gadolinium containing chelates by plants and animals grown in exposed water or on soil irrigated with exposed water was investigated. For this purpose two types of plants were treated with two different contrast agents. The uptake of the Gd contrast agents was studied by monitoring the elemental distribution with laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). This technique allows the multi-elemental analysis of solid samples with high resolution and little sample preparation. The analysis of L. minor showed that the uptake of Gd correlated with the concentration of gadodiamide in the water. The higher the concentration in the exposed water, the larger the Gd signal in the LA-ICP-MS acquired image. Exposure time experiments showed saturation within one day. The L. minor had contact with the CAs through roots and fronds, whereas the L. sativum only showed uptake through the roots. These results show that an external absorption of the CA through the leaves of L. sativum was impossible. All the analyzed parts of the plant showed Gd signal from the CA; the highest being at the main vein of the leaf. It is shown that the CAs can be taken up from plants. Furthermore, the uptake and distribution of Gd in Daphnia magna were shown. The exposure via cultivation medium is followed by Gd signals on the skin and in the area of the intestine, while the uptake via exposed nutrition algae causes the significantly highest Gd intensities in the area of the intestine. Because there are hints of negative effects for human organism these findings are important as they show that Gd based CAs may reach the human food chain via plants and animals growing in contaminated water or plants growing in fields which are irrigated with surface water.

Rapid determination of X-ray contrast agent iomeprol in human plasma by on-line solid-phase extraction coupled with phase optimized liquid chromatography.

Phase optimized liquid chromatography (POPLC) allows for the optimized combination of column segments of any length and stationary phases with different functionalities. In this study, a simple and rapid method using POPLC coupled with on-line solid-phase extraction (SPE) for the analysis of X-ray contrast media agent iomeprol (IOM) in human plasma was developed. Because the phenyl (PH) stationary phase has strong hydrophobic and π-π interactions with IOM and iopromide (IOP, internal standard), the best separation efficiency was achieved with a 250mm×3mm homogenous PH POPLC-column. Different kinds of on-line SPE sorbents were studied, including restricted access material-alkyl diol silica (ADS), LiChrolut EN with excellent absorption capacity and hydrophilic-lipophilic-balanced Oasis HLB. The most efficient on-line sample clean-up was carried out using a fast-flow on-line purification approach with an Oasis HLB pre-column ((20mm×2mm, 30µm). This pre-column showed excellent durability and reproducibility. At least 400 samples could be analyzed with one pre-column. Each plasma sample was directly injected and analyzed within 15min. The calibration curves were linear in the range of 10-1000µg/mL. The limit of quantitation was 2.26µg/mL. The inter-day precision of this method was excellent and less than 1.44%, and the intra-day precision was less than 4.44%. The inter-day and intra-day accuracy ranged from 94.33% to 104.36% and 94.60% to 101.71%, respectively. This validated method is expected to be useful in the analysis of human plasma samples for glomerular filtration rate (GFR) measurements and assessment of kidney function.

Removal of the iodinated X-ray contrast medium diatrizoate by anaerobic transformation.

The iodinated X-ray contrast medium diatrizoate is known to be very persistent in current wastewater treatment as well as in environmental compartments. In this study, the potential of anaerobic processes in soils, sediments, and during wastewater treatment to remove and transform diatrizoate was investigated. In anaerobic batch experiments with soil and sediment seven biologically formed transformation products (TPs) as well as the corresponding transformation pathway were identified. The TPs resulted from successive deiodinations and deacetylations. The final TP 3,5-diaminobenzoic acid (DABA) was stable under anaerobic conditions. However, DABA was further transformed under air atmosphere, indicating the potential for the mineralization of diatrizoate by combining anaerobic and aerobic conditions. With the development of a methodology using complementary liquid chromatography-electrospray ionization-tandem mass spectrometry and liquid chromatography-inductively coupled plasma-mass spectrometry techniques, all identified TPs were quantified and the mass balance could be closed without having authentic standards for four of the TPs available. The detection and quantification of diatrizoate TPs in groundwater, in technical wetlands with anaerobic zones, and in a pilot wastewater treatment plant established for anaerobic treatment highlights the transferability and up-scaling of the results attained by laboratory experiments to environmental conditions.

Separation of Gd-humic complexes and Gd-based magnetic resonance imaging contrast agent in river water with QAE-Sephadex A-25 for the fractionation analysis.

Gadolinium complexed with naturally occurring, negatively charged humic substances (humic and fulvic acids) was collected from 500 mL of sample solution onto a column packed with 150 mg of a strongly basic anion-exchanger (QAE-Sephadex A-25). A Gd-based magnetic resonance imaging contrast agent (diethylenetriamine-N,N,N',N″,N″-pentaacetato aquo gadolinium(III), Gd-DTPA(2-)) was simultaneously collected on the same column. The Gd-DTPA complex was desorbed by anion-exchange with 50mM tetramethylammonium sulfate, leaving the Gd-humic complexes on the column. The Gd-humic complexes were subsequently dissociated with 1M nitric acid to desorb the humic fraction of Gd. The two-step desorption with small volumes of the eluting agents allowed the 100-fold preconcentration for the fractionation analysis of Gd at low ng L(-1) levels by inductively coupled plasma-mass spectrometry (ICP-MS). On the other hand, Gd(III) neither complexed with humic substances nor DTPA, i.e., free species, was not sorbed on the column. The free Gd in the effluent was preconcentrated 100-fold by a conventional solid-phase extraction with an iminodiacetic acid-type chelating resin and determined by ICP-MS. The proposed analytical fractionation method was applied to river water samples.

Encefalopatía transitoria por contraste tras coronariografía que simulaba una hemorragia subaracnoidea / Contrast-induced transitory encephalopathy after coronariography that simulated a subarachnoid haemorrhage

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Conversion rate of para-hydrogen to ortho-hydrogen by oxygen: implications for PHIP gas storage and utilization.

OBJECT: To determine the storability of para-hydrogen before reestablishment of the room temperature thermal equilibrium mixture. MATERIALS AND METHODS: Para-hydrogen was produced at near 100% purity and mixed with different oxygen quantities to determine the rate of conversion to the thermal equilibrium mixture of 75: 25% (ortho: para) by detecting the ortho-hydrogen (1)H nuclear magnetic resonance using a 9.4 T imager. RESULTS: The para-hydrogen to ortho-hydrogen velocity constant, k, near room temperature (292 K) was determined to be 8.27 ± 1.30 L/mol · min(-1). This value was calculated utilizing four different oxygen fractions. CONCLUSIONS: Para-hydrogen conversion to ortho-hydrogen by oxygen can be minimized for long term storage with judicious removal of oxygen contamination. Prior calculated velocity rates were confirmed demonstrating a dependence on only the oxygen concentration.

Removal of the X-ray contrast media diatrizoate by electrochemical reduction and oxidation.

Due to their resistance to biological wastewater treatment, iodinated X-ray contrast media (ICM) have been detected in municipal wastewater effluents at relatively high concentrations (i.e., up to 100 µg L(-1)), with hospitals serving as their main source. To provide a new approach for reducing the concentrations of ICMs in wastewater, electrochemical reduction at three-dimensional graphite felt and graphite felt doped with palladium nanoparticles was examined as a means for deiodination of the common ICM diatrizoate. The presence of palladium nanoparticles significantly enhanced the removal of diatrizoate and enabled its complete deiodination to 3,5-diacetamidobenzoic acid. When the system was employed in the treatment of hospital wastewater, diatrizoate was reduced, but the extent of electrochemical reduction decreased as a result of competing reactions with solutes in the matrix. Following electrochemical reduction of diatrizoate to 3,5-diacetamidobenzoic acid, electrochemical oxidation with boron-doped diamond (BDD) anodes was employed. 3,5-Diacetamidobenzoic acid disappeared from solution at a rate that was similar to that of diatrizoate, but it was more readily mineralized than the parent compound. When electrochemical reduction and oxidation were coupled in a three-compartment reactor operated in a continuous mode, complete deiodination of diatrizoate was achieved at an applied cathode potential of -1.7 V vs SHE, with the released iodide ions electrodialyzed in a central compartment with 80% efficiency. The resulting BDD anode potential (i.e., +3.4-3.5 V vs SHE) enabled efficient oxidation of the products of the reductive step. The presence of other anions (e.g., chloride) was likely responsible for a decrease in I(-) separation efficiency when hospital wastewater was treated. Reductive deiodination combined with oxidative degradation provides benefits over oxidative treatment methods because it does not produce stable iodinated intermediates. Nevertheless, the process must be further optimized for the conditions encountered in hospital wastewater to improve the separation efficiency of halide ions prior to the electrooxidation step.

Determination of iodinated X-ray contrast media in sewage by solid-phase extraction and liquid chromatography tandem mass spectrometry.

A method for the quantitative determination of five iodinated X-ray contrast media (ICMs) in sewage was developed by solid-phase extraction and high-performance liquid chromatography-tandem mass spectrometry. A fused-core analytical column was successfully applied for the first time for the separation of ICMs. Oasis HLB was selected from the sorbents tested because of its higher recoveries. The optimized method allowed the determination of the ICMs at low ng/L levels in both influent and effluent sewage, with detection limits of 40 ng/L and 10 ng/L for most compounds in influent and effluent sewage, respectively. The five ICMs studied were determined in all samples analysed, with iopromide being the analyte found at the highest concentration (8.9 µg/L), while iopamidol was the analyte found at lowest concentration (1.3 µg/L) in influent sewage. Effluent sewage did not show a significant decrease in ICM concentrations.

High-pressure, compact, modular radiosynthesizer for production of positron emitting biomarkers.

A robust, modular, semi-automated synthesis unit useful for conducting radiochemical reactions under pressurized conditions (up to ∼200psi [1.4MPa]) for the production of PET biomarkers has been developed. This compact unit (7.6cm×33.0cm×58.4cm) is capable of performing any single step reaction that is generally encountered in radiochemical syntheses, and multiple units can be combined for more complex syntheses. The versatility of a 3-unit system is exemplified by reliably conducting the multi-step syntheses of 2'-deoxy-2'-[(18)F]fluoro-1-ß-arabinofuranosyl-uracil and -cytosine derivatives, which involve corrosive and moisture sensitive reagents under pressurized conditions.

Skin Test–Positive Immediate Hypersensitivity Reaction to Iodinated Contrast Media: The Role of Controlled Challenge Testing

Antecedentes: Aunque clásicamente las reacciones de hipersensibilidad inmediatas (RHI) a medios de contraste iodados (MCI) se han considerado no alérgicas, la publicación creciente de pruebas cutáneas y test de activación de basófilos positivos, sugieren un mecanismo alérgico específico en algunos pacientes. Se han propuesto las pruebas cutáneas como una herramienta útil para el diagnóstico, aunque su sensibilidad y valores predictivos están aún por conocer. El papel de la prueba de provocación controlada no se ha determinado. Objetivo: El objetivo fue evaluar el papel de la prueba de provocación controlada en las RHI a MCI con prueba cutánea positiva. Pacientes y Métodos: Evaluamos 106 pacientes con RHI a MCI mediante prueba cutánea con el contraste que causó la reacción. Se seleccionaron los pacientes con resultado positivo: se ampliaron las pruebas cutáneas con una serie de 8 MCI; en 5 pacientes se realizó prueba de provocación controlada con un MCI alternativo con resultado negativo en la prueba cutánea; otros dos pacientes se sometieron a una tomografía computarizada con un MCI alternativo con resultado negativo en la prueba cutánea. No se administró ninguna premedicación. Resultados: Las pruebas intradérmicas fueron positivas al MCI que causó la reacción en 11 de 106 pacientes (10.4%). Cinco de ellos toleraron la prueba de provocación controlada con un MCI alternativo con resultado negativo en la prueba cutánea. Los otros 2 pacientes a los que se les realizó una tomografía computarizada con un MCI alternativo con prueba cutánea negativa, también lo toleraron. Conclusiones: Las pruebas cutáneas son útiles para la valoración diagnóstica en las RHI alérgicas a MCI. Dado que en muchos pacientes los MCI no pueden ser evitados al ser irremplazables para algunas técnicas diagnósticas o terapéuticas, es necesario identificar un MCI alternativo para ser utilizado con seguridad en procedimientos futuros. Proponemos el uso de la prueba de provocación controlada basada en los resultados de las pruebas cutáneas para resolver esta situación en estas reacciones con prueba cutánea positiva, para poder identificar un MCI alternativo sin reactividad cruzada (AU)

Background: Immediate hypersensitivity reactions (IHR) to iodinated contrast media (ICM) have traditionally been considered nonallergic; however, the increasingly frequent reporting of positive skin test and basophil activation test results suggests a specific allergic mechanism in some patients. Skin tests have been proposed as a useful tool for diagnosis, although their sensitivity and predictive values remain to be determined. The role of controlled challenge testing has not been assessed. Objective: We aimed to evaluate the role of controlled challenge testing in skin test–positive IHR to ICM. Patients and Methods: We evaluated 106 patients with IHR to ICM by performing skin tests with the agent that caused the reaction. Patients with a positive result were selected. Skin tests were extended to a series of 8 ICMs; 5 patients underwent controlled challenge test with an alternative skin test–negative ICM; a further 2 patients underwent computed tomography with an alternative skin test–negative ICM. No premedication was administered. Results: Intradermal test results were positive to the ICM that caused the reaction in 11 out of 106 patients (10.4%). Five of the 11 patients tolerated a controlled challenge test with an alternative skin test–negative ICM. The 2 patients who underwent computed tomography with an alternative skin test–negative ICM tolerated the medium. Conclusions: Skin tests are useful for the diagnostic workup in patients with an allergic IHR to ICM. Since ICM cannot be avoided in many patients because they are irreplaceable in some diagnostic or therapeutic techniques, an alternative safe ICM should be investigated for future procedures. We propose the use of controlled challenge tests based on skin test results to address this need in skin test–positive reactions in order to identify an alternative non–cross-reactive ICM (AU)

An exploratory study of contrast agents for soft tissue visualization by means of high resolution X-ray computed tomography imaging.

High resolution X-ray computed tomography (CT), or microCT, is a promising and already widely used technique in various scientific fields. Also for histological purposes it has great potential. Although microCT has proven to be a valuable technique for the imaging of bone structures, the visualization of soft tissue structures is still an important challenge due to their low inherent X-ray contrast. One way to achieve contrast enhancement is to make use of contrast agents. However, contrary to light and electron microscopy, knowledge about contrast agents and staining procedures is limited for X-ray CT. The purpose of this paper is to identify useful X-ray contrast agents for soft tissue visualization, which can be applied in a simple way and are also suited for samples larger than (1 cm)(3) . And 28 chemical substances have been investigated. All chemicals were applied in the form of concentrated aqueous solutions in which the samples were immersed. First, strips of green Bacon were stained to evaluate contrast enhancement between muscle and adipose tissue. Furthermore it was also tested whether the contrast agents remained fixed in the tissue after staining by re-immersing them in water. Based on the results, 12 contrast agents were selected for further testing on postmortem mice hind legs, containing a variety of different tissues, including muscle, fat, bone, cartilage and tendons. It was evaluated whether the contrast agents allowed a clearer distinction between the different soft tissue structures present. Finally also penetration depth was measured. And 26 chemicals resulted in contrast enhancement between muscle and adipose tissue in the Bacon strips. Mercury(II)chloride (HgCl2 ), phosphotungstic acid (PTA), phosphomolybdic acid (PMA) and ammonium orthomolybdate ((NH4 )2 MoO4 ) remained fixed after re-immersion in water. The penetration tests showed that potassium iodide (KI) and sodium tungstate can be most efficiently used for large samples of the order of several tens of cm(3) . PMA, PTA, HgCl2 and also to a lesser extent Na2 WO4 and (NH4 )2 MoO4 allowed a clearer distinction between the different soft tissue structures present.

Speciation of gadolinium in surface water samples and plants by hydrophilic interaction chromatography hyphenated with inductively coupled plasma mass spectrometry.

Hydrophilic interaction chromatography (HILIC) coupled with inductively coupled plasma mass spectrometry (ICP-MS) was optimized for speciation analysis of gadolinium-based contrast agents in environmental samples, in particular surface river waters and plants. Surface water samples from the Teltow channel, near Berlin, were investigated over a distance of 5 km downstream from the influx of a wastewater treatment plant. The total concentration of gadolinium increased significantly from 50 to 990 ng L(-1) due to the influx of the contrast agents. After complete mixing with the river water, the concentration remained constant over a distance of at least 4 km. Two main substances [Dotarem(®) (Gd-DOTA) and Gadovist(®) (Gd-BT-DO3A)] have been identified in the river water using standards. A gadolinium-based contrast agent, possibly Gd-DOTA (Dotarem(®)), was also detected in water plant samples taken from the Teltow channel. Therefore, uptake of contrast agents [Gadovist(®) (Gd-BTDO3A), Magnevist(®) (Gd-DTPA), Omniscan(®) (Gd-DTPA-BMA), Dotarem(®) (Gd-DOTA), and Multihance(®) (Gd-BOPTA)] by plants was investigated in a model experiment using Lepidium sativum (cress plants). HILIC-ICP-MS was used for identification of different contrast agents, and a first approach for quantification using aqueous standard solutions was tested. For speciation analysis, all investigated contrast agents could be extracted from the plant tissues with a recovery of about 54 % for Multihance(®) (Gd-BOPTA) up to 106 % for Gadovist(®) (Gd-BT-DO3A). These experiments demonstrate that all contrast agents investigated are transported from the roots to the leaves where the highest content was measured.

68Ga-autoclabeling of DOTA-TATE and DOTA-NOC.

INTRODUCTION: A new method combining (68)Ga-labeling and steam sterilization, here called autoclabeling, has been evaluated for two somatostatin receptor binding tracers used for positron emission tomography (PET) imaging of neuroendocrine tumors; DOTA-TATE and -NOC. METHODS: The two peptides DOTA-TATE and -NOC were labeled with (68)Ga by heating for 15 min at 121°C in the presence of acetate buffer at pH 4.3. The product solutions were tested for sterility, presence of endotoxins, degradation of peptide and osmolality. RESULTS: Complete incorporation of (68)Ga was obtained after the autoclabeling reaction and no degradation of the peptides was observed. Sterility was verified and the presence of endotoxins was well within Ph. Eur limits (175IU/maximum injected volume). CONCLUSIONS: The autoclabeling method provides a convenient procedure for (68)Ga-labeling by combining the labeling reaction and steam sterilization into one single step.

Recycling of 3He from lung magnetic resonance imaging.

We have developed the means to recycle (3) He exhaled by patients after imaging the lungs using magnetic resonance of hyperpolarized (3) He. The exhaled gas is collected in a helium leak proof bag and further compressed into a steel bottle. The collected gas contains about 1-2% of (3) He, depending on the amount administered and the number of breaths collected to wash out the (3) He gas from the lungs. (3) He is separated from the exhaled air using zeolite molecular sieve adsorbent at 77 K followed by a cold head at 8 K. Residual gaseous impurities are finally absorbed by a commercial nonevaporative getter. The recycled (3) He gas features high purity, which is required for repolarization by metastability exchange optical pumping. At present, we achieve a collection efficiency of 80-84% for exhaled gas from healthy volunteers and cryogenic separation efficiency of 95%.

Simulation and source identification of X-ray contrast media in the water cycle of Berlin.

This article describes the development of a model to simulate the fate of iodinated X-ray contrast media (XRC) in the water cycle of the German capital, Berlin. It also handles data uncertainties concerning the different amounts and sources of input for XRC via source densities in single districts for the XRC usage by inhabitants, hospitals, and radiologists. As well, different degradation rates for the behavior of the adsorbable organic iodine (AOI) were investigated in single water compartments. The introduced model consists of mass balances and includes, in addition to naturally branched bodies of water, the water distribution network between waterways and wastewater treatment plants, which are coupled to natural surface waters at numerous points. Scenarios were calculated according to the data uncertainties that were statistically evaluated to identify the scenario with the highest agreement among the provided measurement data. The simulation of X-ray contrast media in the water cycle of Berlin showed that medical institutions have to be considered as point sources for congested urban areas due to their high levels of X-ray contrast media emission. The calculations identified hospitals, represented by their capacity (number of hospital beds), as the most relevant point sources, while the inhabitants served as important diffusive sources. Deployed for almost inert substances like contrast media, the model can be used for qualitative statements and, therefore, as a decision-support tool.

Preparation, purification, and characterization of lanthanide complexes for use as contrast agents for magnetic resonance imaging.

Polyaminopolycarboxylate-based ligands are commonly used to chelate lanthanide ions, and the resulting complexes are useful as contrast agents for magnetic resonance imaging (MRI). Many commercially available ligands are especially useful because they contain functional groups that allow for fast, high-purity, and high-yielding conjugation to macromolecules and biomolecules via amine-reactive activated esters and isothiocyanate groups or thiol-reactive maleimides. While metalation of these ligands is considered common knowledge in the field of bioconjugation chemistry, subtle differences in metalation procedures must be taken into account when selecting metal starting materials. Furthermore, multiple options for purification and characterization exist, and selection of the most effective procedure partially depends on the selection of starting materials. These subtle differences are often neglected in published protocols. Here, our goal is to demonstrate common methods for metalation, purification, and characterization of lanthanide complexes that can be used as contrast agents for MRI (Figure 1). We expect that this publication will enable biomedical scientists to incorporate lanthanide complexation reactions into their repertoire of commonly used reactions by easing the selection of starting materials and purification methods.