scholarly journals Isolated Perfused Rat Livers to Quantify the Pharmacokinetics and Concentrations of Gd-BOPTA

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Catherine M. Pastor
Keyword(s):  
Contrast Agent ◽  
Contrast Agents ◽  
Image Interpretation ◽  
Gadobenate Dimeglumine ◽  
Pharmacokinetic Parameters ◽  
Liver Imaging ◽  
Transfer Rates ◽  
Set Up ◽  
Rat Livers

With recent advances in liver imaging, the estimation of liver concentrations is now possible following the injection of hepatobiliary contrast agents and radiotracers. However, how these images are generated remains partially unknown. Most experiments that would be helpful to increase this understanding cannot be performed in vivo. For these reasons, we investigated the liver distribution of the magnetic resonance (MR) contrast agent gadobenate dimeglumine (Gd-BOPTA, MultiHance®, Bracco Imaging) in isolated perfused rat livers (IPRLs). In IPRL, we developed a new set up that quantifies simultaneously the Gd-BOPTA compartment concentrations and the transfer rates between these compartments. Concentrations were measured either by MR signal intensity or by count rates when the contrast agent was labelled by [153Gd]. With this experimental model, we show how the Gd-BOPTA hepatocyte concentrations are modified by temperature and liver flow rates. We define new pharmacokinetic parameters to quantify the canalicular transport of Gd-BOPTA. Finally, we present how transfer rates generate Gd-BOPTA concentrations in rat liver compartments. These findings better explain how liver imaging with hepatobiliary radiotracers and contrast agents is generated and improve the image interpretation by clinicians.

scholarly journals Steatosis Alters the Activity of Hepatocyte Membrane Transporters in Obese Rats

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2733
Author(s):  
Catherine M Pastor ◽  
Valérie Vilgrain
Keyword(s):  
Contrast Agent ◽  
Experimental Model ◽  
Liver Diseases ◽  
Gadobenate Dimeglumine ◽  
Membrane Transporters ◽  
Liver Imaging ◽  
Fat Accumulation ◽  
Obese Rats ◽  
Rat Livers ◽  
Gamma Counter

Fat accumulation (steatosis) in ballooned hepatocytes alters the expression of membrane transporters in Zucker fatty (fa/fa) rats. The aim of the study was to quantify the functions of these transporters and their impact on hepatocyte concentrations using a clinical hepatobiliary contrast agent (Gadobenate dimeglumine, BOPTA) for liver imaging. In isolated and perfused rat livers, we quantified BOPTA accumulation and decay profiles in fa/+ (normal) and fa/fa hepatocytes by placing a gamma counter over livers. Profiles of BOPTA accumulation and decay in hepatocytes were analysed with nonlinear regressions to characterise BOPTA influx and efflux across hepatocyte transporters. At the end of the accumulation period, BOPTA hepatocyte concentrations and influx clearances were not significantly different in fa/+ and fa/fa livers. In contrast, bile clearance was significantly lower in fatty hepatocytes while efflux clearance back to sinusoids compensated the low efflux into canaliculi. The time when BOPTA cellular efflux impacts the accumulation profile of hepatocyte concentrations was slightly delayed (2 min) by steatosis, anticipating a delayed emptying of hepatocytes. The experimental model is useful for quantifying the functions of hepatocyte transporters in liver diseases.

scholarly journals Concentrations and pharmacokinetic parameters of MRI and SPECT hepatobiliary agents in rat liver compartments

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Catherine M. Pastor ◽  
Florian Joly ◽  
Valérie Vilgrain ◽  
Philippe Millet
Keyword(s):  
Ex Vivo ◽  
Volume Ratio ◽  
Gadobenate Dimeglumine ◽  
Extraction Ratio ◽  
Pharmacokinetic Parameters ◽  
Bile Canaliculi ◽  
Canalicular Transporters ◽  
Rat Livers ◽  
Hepatobiliary Agents

Abstract Background In hepatobiliary imaging, systems detect the total amount of agents originating from extracellular space, bile canaliculi, and hepatocytes. They add in situ concentration of each compartment corrected by its respective volume ratio to provide liver concentrations. In vivo contribution of each compartment to liver concentration is inaccessible. Our aim was to quantify the compartmental distribution of two hepatobiliary agents in an ex vivo model and determine how their liver extraction ratios and cholestasis (livers lacking canalicular transporters) might modify it. Methods We perfused labelled gadobenate dimeglumine (Bopta, 200 μM, 7% liver extraction ratio) and mebrofenin (Meb, 64 μM, 94% liver extraction ratio) in normal (n = 18) and cholestatic (n = 6) rat livers. We quantified liver concentrations with a gamma counter placed over livers. Concentrations in hepatocytes and bile canaliculi were calculated. Mann-Whitney and Kruskal-Wallis tests were used. Results Hepatocyte concentrations were 2,043 ± 333 μM (Meb) versus 360 ± 69 μM (Bopta, p < 0.001). Meb extracellular concentrations did not contribute to liver concentrations (1.3 ± 0.3%). The contribution of Bopta extracellular concentration was 12.4 ± 1.9% (p < 0.001 versus Meb). Contribution of canaliculi was similar for both agents (16%). Cholestatic livers had no Bopta in canaliculi but their hepatocyte concentrations increased in comparison to normal livers. Conclusion Hepatocyte concentrations are correlated to liver extraction ratios of hepatobiliary agents. When Bopta is not present in canaliculi of cholestatic livers, hepatocyte concentrations increase in comparison to normal livers. This new understanding extends the interpretation of clinical liver images.

scholarly journals Study on Establishing Reference Safe Concentrations of MRI Contrast Agents for Optimized Images: Paramagnetic Gd-DTPA-BMEA and Superparamagnetic Ferucarbotran

2021 ◽  
Vol 11 (3) ◽  
pp. 1165
Author(s):  
Wen-Tien Hsiao ◽  
Yi-Hong Chou ◽  
Jhong-Wei Tu ◽  
Ai-Yih Wang ◽  
Lu-Han Lai
Keyword(s):  
Contrast Agent ◽  
Contrast Agents ◽  
Mri Contrast Agents ◽  
Mri Contrast Agent ◽  
In Vitro Experiments ◽  
Mri Contrast ◽  
In Vivo Experiments ◽  
Contrast Agent Injection

The purpose of this study is to establish the minimal injection doses of magnetic resonance imaging (MRI) contrast agents that can achieve optimized images while improving the safety of injectable MRI drugs. Gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA) and ferucarbotran, commonly used in clinical practice, were selected and evaluated with in vitro and in vivo experiments. MRI was acquired using T1-weighted (T1W) and T2-weighted (T2W) sequences, and the results were quantitatively analyzed. For in vitro experiments, results showed that T1W and T2W images were optimal when Gd-DTPA-bisamide (2-oxoethyl) (Gd-DTPA-BMEA) and ferucarbotran were diluted to a volume percentage of 0.6% and 0.05%; all comparisons were significant differences in grayscale statistics using one-way analysis of variance (ANOVA). For in vivo experiments, the contrast agent with optimal concentration percentages determined from in vitro experiments were injected into mice with an injection volume of 100 μL, and the images of brain, heart, liver, and mesentery before and after injection were compared. The statistical results showed that the p values of both T1W and T2W were less than 0.001, which were statistically significant. Under safety considerations for MRI contrast agent injection, optimized MRI images could still be obtained after reducing the injection concentration, which can provide a reference for the safety concentrations of MRI contrast agent injection in the future.

PEGylated Gd(OH)3 nanorods as metabolizable contrast agents for computed tomography imaging

2015 ◽  
Vol 39 (11) ◽  
pp. 8999-9005 ◽  
Author(s):  
Yingda Du ◽  
Ming Xing ◽  
Zhiman Li ◽  
Wei Guo
Keyword(s):  
Computed Tomography ◽  
Contrast Agent ◽  
Contrast Agents ◽  
Computed Tomography Imaging ◽  
Hydrothermal Route ◽  
Tomography Imaging

PEGylated Gd(OH)3 nanorods have been efficiently prepared via a facile and green hydrothermal route and used as a metabolizable computed tomography contrast agent for in vivo imaging.

Targeted tumor MRI with gadobutrol-loaded anti-HER2 immunoliposomes

2016 ◽  
Vol 58 (5) ◽  
pp. 573-580 ◽  
Author(s):  
Weicui Chen ◽  
Bo Liu ◽  
Jun Chen ◽  
Guoqing Liu ◽  
Xian Liu
Keyword(s):  
Contrast Agent ◽  
Contrast Agents ◽  
Signal To Noise Ratio ◽  
Cellular Level ◽  
Cancer Tissue ◽  
Post Injection ◽  
Specific Tumor ◽  
Noise Ratio ◽  
Targeted Contrast Agent

Background Immunoliposomes have been used to deliver MR contrast agents to cancer tissue by targeting tumor associated antigens, thus enabling the visualization of biological processes at the cellular level. Purpose To develop and evaluate the feasibility of specific HER2 targeted liposomal MR contrast agent. Material and Methods Gd-loaded anti-HER2 immunolipomes (Gd-ILs) and non-targeted PEGylated liposomes (Gd-NTLs) were prepared and characterized. Tumor bearing animals were randomized into three groups: Gd- ILs, Gd- NTLs and gadobutrol. Animals were imaged prior and 5, 15, 60, 120 and 180 min after i.v. injection of different contrast agents. The signal intensity enhancement percentage, signal- to- noise ratio and contrast- to –noise ratio was used to qualify tumor enhancement of different groups. After imaging, tumors were excised for histological examination. Results In vivo dynamic MR images, the specific targeted contrast agent bound to tumor tissue and result in a gradual and persisting enhancement for at least 3 hours in mice bearing tumor xenografts, reaching a maximum of 87.7% enhancement after 120 min post-injection. Gd-ILs demonstrated superior tumor enhancement over control non target contrast agent and gadobutrol in HER2 overexpressing tumors at 60, 120 and 180 min post- injection. The SNR and CNR of Gd-ILs in the tumors were significantly greater than that of Gd-NTLs at 60, 120, 180 min post- injection. Conclusion The results indicate the feasibility of Gd-ILs providing prolonged circulation, specific tumor enhancement and cancer cell recognition as targeted contrast agent.

Evaluation of gadoxetate disodium as a contrast agent for mouse liver imaging: comparison with gadobenate dimeglumine

2009 ◽  
Vol 27 (1) ◽  
pp. 101-107 ◽  
Author(s):  
Shigeru Kiryu ◽  
Yusuke Inoue ◽  
Makoto Watanabe ◽  
Kiyoko Izawa ◽  
Morio Shimada ◽  
...  
Keyword(s):  
Contrast Agent ◽  
Mouse Liver ◽  
Gadobenate Dimeglumine ◽  
Liver Imaging ◽  
Gadoxetate Disodium

scholarly journals Protein MRI contrast agent with unprecedented metal selectivity and sensitivity for liver cancer imaging

2015 ◽  
Vol 112 (21) ◽  
pp. 6607-6612 ◽  
Author(s):  
Shenghui Xue ◽  
Hua Yang ◽  
Jingjuan Qiao ◽  
Fan Pu ◽  
Jie Jiang ◽  
...  
Keyword(s):  
Contrast Agent ◽  
Contrast Agents ◽  
Mri Contrast Agent ◽  
Therapeutic Interventions ◽  
Mri Contrast ◽  
Liver Cancers ◽  
Poor Treatment ◽  
Ratio Imaging ◽  
Metastatic Liver

With available MRI techniques, primary and metastatic liver cancers that are associated with high mortality rates and poor treatment responses are only diagnosed at late stages, due to the lack of highly sensitive contrast agents without Gd3+ toxicity. We have developed a protein contrast agent (ProCA32) that exhibits high stability for Gd3+ and a 1011-fold greater selectivity for Gd3+ over Zn2+ compared with existing contrast agents. ProCA32, modified from parvalbumin, possesses high relaxivities (r1/r2: 66.8 mmol−1⋅s−1/89.2 mmol−1⋅s−1 per particle). Using T1- and T2-weighted, as well as T2/T1 ratio imaging, we have achieved, for the first time (to our knowledge), robust MRI detection of early liver metastases as small as ∼0.24 mm in diameter, much smaller than the current detection limit of 10–20 mm. Furthermore, ProCA32 exhibits appropriate in vivo preference for liver sinusoidal spaces and pharmacokinetics for high-quality imaging. ProCA32 will be invaluable for noninvasive early detection of primary and metastatic liver cancers as well as for monitoring treatment and guiding therapeutic interventions, including drug delivery.

scholarly journals PEG-modified gadolinium nanoparticles as contrast agents for in vivo micro-CT

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Charmainne Cruje ◽  
P. Joy Dunmore-Buyze ◽  
Eric Grolman ◽  
David W. Holdsworth ◽  
Elizabeth R. Gillies ◽  
...  
Keyword(s):  
Contrast Agent ◽  
Contrast Agents ◽  
Soft Tissues ◽  
Three Dimensional ◽  
Blood Pool ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Poly Ethylene

AbstractVascular research is largely performed in rodents with the goal of developing treatments for human disease. Micro-computed tomography (micro-CT) provides non-destructive three-dimensional imaging that can be used to study the vasculature of rodents. However, to distinguish vasculature from other soft tissues, long-circulating contrast agents are required. In this study, we demonstrated that poly(ethylene glycol) (PEG)-coated gadolinium nanoparticles can be used as a vascular contrast agent in micro-CT. The coated particles could be lyophilized and then redispersed in an aqueous solution to achieve 100 mg/mL of gadolinium. After an intravenous injection of the contrast agent into mice, micro-CT scans showed blood pool contrast enhancements of at least 200 HU for 30 min. Imaging and quantitative analysis of gadolinium in tissues showed the presence of contrast agent in clearance organs including the liver and spleen and very low amounts in other organs. In vitro cell culture experiments, subcutaneous injections, and analysis of mouse body weight suggested that the agents exhibited low toxicity. Histological analysis of tissues 5 days after injection of the contrast agent showed cytotoxicity in the spleen, but no abnormalities were observed in the liver, lungs, kidneys, and bladder.

scholarly journals X-ray-based virtual slicing of TB-infected lungs

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ana Ortega-Gil ◽  
Juan José Vaquero ◽  
Mario Gonzalez-Arjona ◽  
Joaquín Rullas ◽  
Arrate Muñoz-Barrutia
Keyword(s):  
Contrast Agent ◽  
Contrast Agents ◽  
3D Visualization ◽  
Post Mortem ◽  
Micro Ct ◽  
Micro Computed Tomography ◽  
Preclinical Research ◽  
X Ray ◽  
The Right

AbstractHollow organs such as the lungs pose a considerable challenge for post-mortem imaging in preclinical research owing to their extremely low contrast and high structural complexity. The aim of our study was to enhance the contrast of tuberculosis lesions for their stratification by 3D x-ray–based virtual slicing. Organ samples were taken from five control and five tuberculosis-infected mice. Micro-Computed Tomography (CT) scans of the subjects were acquired in vivo (without contrast agent) and post-mortem (with contrast agent). The proposed contrast-enhancing technique consists of x-ray contrast agent uptake (silver nitrate and iodine) by immersion. To create the histology ground-truth, the CT scan of the paraffin block guided the sectioning towards specific planes of interest. The digitalized histological slides reveal the presence, extent, and appearance of the contrast agents in lung structures and organized aggregates of immune cells. These findings correlate with the contrast-enhanced micro-CT slice. The abnormal densities in the lungs due to tuberculosis disease are concentrated in the right tail of the lung intensity histograms. The increase in the width of the right tail (~376%) indicates a contrast enhancement of the details of the abnormal densities. Postmortem contrast agents enhance the x-ray attenuation in tuberculosis lesions to allow 3D visualization by polychromatic x-ray CT, providing an advantageous tool for virtual slicing of whole lungs. The proposed contrast-enhancing technique combined with computational methods and the diverse micro-CT modalities will open the doors to the stratification of lesion types associated with infectious diseases.

Molybdenum Dioxide (MoS2)/Gadolinium (Gd) Containing Arginine-Glycine-Aspartic Acid (RGD) Sequences as New Nano-Contrast Agent for Cancer Magnetic Resonance Imaging (MRI)

2021 ◽  
Vol 21 (3) ◽  
pp. 1403-1412
Author(s):  
Xiaoguang Hao ◽  
Weijing Li
Keyword(s):  
Particle Size ◽  
Contrast Agent ◽  
Contrast Agents ◽  
Aspartic Acid ◽  
Nude Mice ◽  
Molybdenum Dioxide ◽  
Signal Value ◽  
Arginine Glycine Aspartic Acid

Molybdenum dioxide-gadolinium-arginine/glycine/aspartic acid (MoS2-Gd-RGD) sequences targeting nano-contrast agents that specifically bind to human hepatocellular carcinoma (HCC) HepG2 cells were synthesized, and their targeting imaging effects on HCC cells and models were evaluated. Zeta potential, particle size and Fourier Transform Infrared Spectrometer (FTIR) were used to characterize the nano-contrast agent, and its cytotoxicity was evaluated. The MoS2-Gd nanoparticles were used as control in vitro to determine the targeting capability of the MoS2-Gd-RGD nanoparticles toward integrin αvβ3. During in vivo animal experiments, 12 nude mice with tumors were randomly divided into three groups to compare the imaging effects of the MoS2-Gd-RGD and MoS2-Gd groups. The hydrodynamic diameter of MoS2-Gd-RGD nanoparticles was approximately 336.43±6.43 nm, and the polydispersity index (PDI) value reached 0.132. Transmission electron microscopy showed the uniform particle size and good dispersion of the nanoparticles. The relaxation rate totaled 1.39 mM−1S−1. The signal value of the T1-weighted image of the HepG2 cells treated with MoS2-Gd-RGD was higher than that of the non-targeted materials (MoS2-Gd) (P < 0.01). The signal value of the tumor increased significantly 15 min after the tail vein injection with MoS2-Gd-RGD, and it peaked at 60 min after injection. A significant difference in tumor signal values was observed between the two groups of nude mice injected with MoS2-Gd-RGD and MoS2- Gd (P < 0.01). At the in vitro and in vivo experiments, the MoS2-Gd-RGD nanoparticles presented the characteristics of integrin αvβ3 targeting. Thus, MoS2-Gd-RGD nanoparticles feature potential as contrast agents for MRI.

Sign in / Sign up

Export Citation Format

Share Document