Objectives: The aim of this study was to investigate the impact of impaired renal function on gadolinium (Gd) retention in various organs after Gd-based contrast agent injection. Materials and Methods: After local animal care and review committee approval, 23 normal mice and 26 with renal failure were divided into 4 treatment groups (Gd-DTPA-BMA, 5 mmol/kg; Gd-DOTA, 5 mmol/kg; GdCl₃, 0.02 mmol/kg; and saline, 250 μL). Each agent was intravenously administered on weekdays for 4 weeks. Samples were collected on days 3 (short-term) and 45 (long-term) after the last injection. Gadolinium concentrations were quantified by inductively coupled plasma-mass spectrometry. Results: Three mice with renal failure and 2 normal mice in the GdCl₃ group and 1 mouse with renal failure in the Gd-DTPA-BMA group died. In the Gd-DTPA-BMA group, impaired renal function increased short-term Gd retention in the liver, bone, spleen, skin, and kidney (P < 0.01) but did not affect long-term Gd retention. Gd-DTPA-BMA showed higher Gd retention than Gd-DOTA. Although Gd retention in the Gd-DOTA group was generally low, impaired renal function increased only long-term hepatic Gd retention. Hepatic and splenic Gd retentions were significantly higher than other organs' Gd retention in the GdCl₃ group (P < 0.01). Renal function did not affect brain Gd retention, regardless of the Gd compound used. Conclusions: The tendency of Gd retention varied according to the agent, regardless of renal function. Although renal impairment increased short-term Gd retention after Gd-DTPA-BMA administration, long-term Gd retention for Gd-based contrast agents was almost unaffected by renal function, suggesting that the chemical structures of retained Gd may not be consistent and some Gd is slowly eliminated after initially being retained.

Objectives:To investigate the distribution and clearance of retained gadolinium (Gd) in various parts of the brain after intravenously administering a Gd-based contrast agent (GBCA) in normal and renal failure mouse models.Materials and Methods:Two different mouse models: normal (n = 12) and renal failure (n = 12) were used. Clinical GBCAs (Gd-DTPA-BMA, 5 mmol/kg or Gd-DOTA, 5 mmol/kg) were intravenously administered five times per week for 4 weeks. Both groups were divided into two subgroups based on the time-point for sample collection: 3 days (3d) and 45 days (45d) after the last injection. Normal saline (5 mL/kg) was intravenously administered to mice of the control groups in the same manner. Samples of the following parts of the mouse brain were obtained on dissection: olfactory bulb, cerebral cortex, hippocampus, thalamus, midbrain, cerebellum, pons and medulla. 158Gd concentrations in each sample were quantified using inductively coupled plasma mass spectrometry.Results:The olfactory bulb had the h...

Backgrounds: Overexpression of epidermal growth factor receptor (EGFR) has been established as a valid therapeutic target of non-small cell lung cancer (NSCLC). However, the clinical benefit of cetuximab as an EGFR-targeting drug is still controversial, partially due to the lack of effective means to identify suitable patients. This study aimed to investigate the potential of radiolabeled cetuximab as a non-invasive tool to predict cetuximab accumulation in NSCLC tumor xenografts with varying EGFR expression levels. Methods: The NSCLC tumors in model mice were subjected to in vivo biodistribution study and positron emission tomography (PET) imaging 48 h after injection of either ¹¹¹In- or ⁶⁴Cu-labeled cetuximab. The EGFR expression levels of NSCLC tumors were determined by ex vivo immunoblotting. Results: We found that tumors with high EGFR expression had significantly higher [¹¹¹In]In-DOTA-cetuximab accumulation than tumors with moderate to low EGFR expression (P < 0.05). Strong correlations were found between [¹¹¹In]In-DOTA-cetuximab tumor uptake and EGFR expression level (r = 0.893), and between [⁶⁴Cu]Cu-DOTA-cetuximab tumor uptake with EGFR expression level (r = 0.915). PET imaging with [⁶⁴Cu]Cu-DOTA-cetuximab allowed clear visualization of tumors. Conclusion: Our findings suggest that this immuno-PET imaging can be clinically translated as a tool to predict cetuximab accumulation in NSCLC cancer patients prior to cetuximab therapy.

Many studies have demonstrated the Eichhornia crassipes (water hyacinth) potency in removing heavy metals, but the plant’s potential for sorption of gadolinium (Gd) has not yet been investigated. In this study, water hyacinth was grown in a glass container for 30 days with either GdCl₃ or Gd-based contrast agent (GBCA; gadoterate) with water obtained from the Tone River. On the day 30, the Gd concentration in both the water and the plants was measured by mass spectrometry (ICP-MS). After 30 days, 98.5% of GdCl₃ in the water had been absorbed by the roots, and 3.5% of Gd was transferred to the leaves. On the other hand, the water hyacinth roots absorbed only 12% of the gadoterate. When exposed to 5 mg/L of GdCl₃, the roots of water hyacinth may effectively remove Gd ions in the aquatic environment, with no visible effect on the general health of the plant. However, the water hyacinth roots did not absorb GBCA. This may result in higher accumulation of Gd in the aqueous environment. The GBCA may be broken down by environmental factors and negatively affect the marine ecosystem. This study highlights the potential capability of water hyacinths in reducing the increasing gadolinium in the environment, which may be of value in optimizing the phytoremediation of medical waste.

Objective: To investigate the role of transporter proteins in gadolinium (Gd) distribution and retention in the brain after one high-dose injection of Gd-based contrast agent (GBCA). Methods and materials: 30 ddY mice were randomly divided into three treatment groups to be intravenously injected with either Gadodiamide (linear GBCA), Gadobutrol (macrocyclic GBCA), or Gadoterate (macrocyclic GBCA) at a dose of 5 mmol/kg, while five mice in the control group received 250 µL saline. Five minutes (5 min) and ten days (10d) post-injection, the cerebrospinal fluid (CSF), choroid plexus (CP), and meninges and associated vasculature (MAV) were collected. The brain was then dissected to obtain the olfactory bulb, cerebral cortex, hippocampus, cerebellum, and brainstem. Proteins were extracted and separated by a size-exclusion high-performance liquid chromatography (SEC) system, and Gd concentrations were quantified by inductively coupled plasma mass spectrometry (ICP-MS). Results: 5 m post-injection, the Gadodiamide group had the highest Gd concentration, while Gadoterate had the lowest Gd concentration in all parts of the brain (p < .05). Gd concentration was highest in the cerebrospinal fluid (CSF) of the Gadodiamide group (578.4 ± 135.3 nmol), while Gd concentration was highest in MAV in the Gadobutrol group (379.7 ± 75.4 nmol) at 5 min post-injection. At 10d, in spite of the significant decrease of Gd from all GBCAs ( p < 0.01), retained Gd from Gadodiamide was detected all over the brain in several molecules that varied in size. Gd from Gadobutrol detected in the olfactory bulb (8.7 ± 4.5 nmol) was significantly higher than in other parts of the brain. Although most Gd from Gadobutrol was found in molecules similar in size to Gadobutrol, it was also found in several protein molecules of molecular size larger than the contrast agents. Only a small amount of Gd from Gadoterate was found in the brain. Conclusion: GBCAs may be able to pass through intact brain barriers, and the chemical structures of GBCAs may affect the penetration capability of Gd into the brain. Retained Gd in the brain tissue from Gadodiamide and Gadobutrol may be bound to some organic molecules, including proteins. Advances in knowledge: Intact GBCA are able to penetrate a series of brain barrier immediately after administration regardless the type of the chelate. Gd may be bound with macromolecules that may cause Gd retention in the brain.