Imaging Contrast Agent Gadolinium Research Articles

Application of tissue-specific magnetic resonance imaging contrast agent gadolinium ethoxybenzyl dimeglumine on precision hepatic surgery

Gadolinium ethoxybenzyl dimeglumine (Gd-EOB-DTPA), a newly applicable hepatocyte-specific contrast agent, can provide both dynamic and hepatobiliary images and has been rapidly accepted by clinicians for the diagnosis of liver lesions and preoperative evaluation. Gd-EOB-DTPA can fulfill hepatic perfusion imaging, detection and characterization of focal liver lesions, evaluation of liver function , and predict biological behaviors of hepatocellular carcinoma (HCC) within the same examination in a relatively short time window. A large number of domestic and foreign studies have confirmed that hepatobiliary-specific enhanced magnetic resonance imaging (MRI) was significantly superior to MRI scan, enhanced CT and ultrasound in diagnosing HCC. With the help of the advanced imaging techniques, surgeons can accurately diagnose and assess the situation of patients to implement individualized treatment plans, and therefore these will promote the development of precision hepatic surgery. Key words: Liver diseases; Precision hepatic surgery; Gadolinium ethoxybenzyl dime-glumine; Magetic resonance imaging

Investigating the Lymphatic System by Dual-Color Elemental Mass Spectrometry Imaging.

Secondary lymphedema accompanied with strong restrictions in quality of life is still major side effects in cancer therapy. Therefore, dedicated diagnostic tools and further investigation of the lymphatic system are crucial to improve lymphedema therapy. In this pilot study, a method for quantitative analysis of the lymphatic system in a rat model by laser ablation (LA) with inductively coupled plasma mass spectrometry imaging (ICP-MSI) is presented. As a possible lymph marker, thulium(III)(1R,4R,7R,10R)-α,α′,α′′,α′′′-tetramethyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (Tm-DOTMA) is introduced and compared to the clinically used magnetic resonance imaging contrast agent gadolinium(III)2,2′,2′′-(10-((2R,3S)-1,3,4-trihydroxybutan-2-yl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate (Gd-DO3A-butrol). Gadobutrol functioned as standard contrast media in MRI lymphangiography to detect lymphatic flow qualitatively. Thus, Tm-DOTMA was investigated as lymphatic marker to detect lymphatic flow quantitatively. Both contrast agents were successfully used to visualize the lymphatic flow in successive lymph nodes in LA-ICP-MS due to lower limits of detection compared to MRI. Furthermore, the distribution of contrast agents by multicolored imaging showed accumulation in specific areas (sectors) of the lymph nodes after application of contrast agents in different areas.

Quantification of river water infiltration in shallow aquifers using acesulfame and anthropogenic gadolinium

This study has investigated the use of the artificial sweetener acesulfame and the magnetic resonance imaging contrast agent gadolinium as quantitative tracers for river water infiltration into shallow groundwater. The influence of a river on alluvial groundwater in a subalpine catchment in western Europe has been assessed using the ‘classical’ hydrochemical tracer chloride and the trace contaminants acesulfame and anthropogenic gadolinium. Mixing ratios for riverine bank filtrate with ambient groundwater and the uncertainties associated with the temporal and spatial tracer variability were calculated using acesulfame and gadolinium and compared with those obtained using chloride. The temporal variability of tracer concentrations in river water of gadolinium (standard deviation SD: 63%) and acesulfame (SD: 71%) both exceeded that of chloride (SD: 27%), and this was identified as the main source of uncertainty in the mixing analysis. Similar spatial distributions were detected in the groundwater for chloride and gadolinium, but not for acesulfame. Mixing analyses using acesulfame resulted in calculated mixing ratios that differed from those obtained using gadolinium and chloride by up to 83% and 92%, respectively. At the investigated site, which had oxic conditions and moderate temperatures, acesulfame was found to be a less reliable tracer than either gadolinium or chloride, probably because of natural attenuation and input from other sources. There was no statistically significant difference between the mixing ratios obtained using chloride or gadolinium, the mixing ratios obtained using gadolinium were 40–50% lower than those obtained using chloride. This is mainly due to a bias of the mean gadolinium concentration in river water towards higher values. In view of the uncertainties of the two tracers, neither could be preferred over the other for the quantification of bank filtrate in groundwater. At this specific site gadolinium was able to reliably identify river water infiltration and was a more precise tracer than chloride at low mixing ratios (<20%), because of the exclusive occurrence of gadolinium in river water and its high dynamic range. Copyright © 2015 John Wiley & Sons, Ltd.

The gastrin/cholecystokinin-B receptor on prostate cells – A novel target for bifunctional prostate cancer imaging

The means of identifying prostate carcinoma and its metastases are limited.The contrast agents used in magnetic resonance imaging clinical diagnostics are not taken up into the tumor cells, but only accumulate in the interstitial space of the highly vasculated tumor.We examined the gastrin/cholecystokinin-B receptor as a possible target for prostate-specific detection using the C-terminal seven amino acid sequence of the gastrin peptide hormone. The correct sequence and a scrambled control sequence were coupled to the fluorescent dye rhodamine and the magnetic resonance imaging contrast agent gadolinium (Gd)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA).Expression analysis of the gastrin receptor mRNA was performed by reverse transcriptase polymerase chain reaction on PC3 prostate carcinoma cells, U373 glioma, U2OS osteosarcoma and Colo205 colon carcinoma cells. After having confirmed elevated expression of gastrin receptor in PC3 cells and very low expression of the receptor in Colo205 cells, these two cell lines were used to create tumor xenografts on nude mice for in vivo experiments.Confocal lasers scanning microscopy and magnetic resonance imaging showed a high specificity of the correct conjugate for the PC3 xenografts. Staining of the PC3 xenografts was much weaker with the scrambled conjugate while the Colo205 xenografts showed no marked staining with any of the conjugates.In vitro experiments comparing the correct and scrambled conjugates on PC3 cells by magnetic resonance relaxometry and fluorescence-activated cell sorting confirmed markedly higher specificity of the correct conjugate.The investigations show that the gastrin receptor is a promising tumor cell surface target for future prostate-cancer-specific imaging applications.

Liposome-based Nanoprobe With Antibody Conjugation Combined With MRI Contrast Encapsulation as a Potential Diagnostic and Therapeutic Agent for Human Head-and-Neck Cancer Cells

Purpose/Objective(s): To develop a tumor-targeting nanoprobe that selectively binds to epidermal growth factor receptor (EGFR) overexpressing tumor cells by encapsulating a magnetic resonance (MR) imaging contrast agent gadolinium (Gd) and conjugating an EGFR-specific monoclonal antibody within liposome particles. Materials/Methods: Encapsulation of Gd within liposome particles was optimized by combining different concentrations of Dipalmitoylphosphatidylcholine (DPPC), cholesterol, 1,2-dipalmitoyl-sn-glycero-3phosphoethanolamine-N-(biotinyl) (Biotinyl PE), and Diethylenetriaminepentaacetic acid-bis(stearylamide)-Gd (DTPA-BSA-Gd). Avidin was included in the liposomal membrane to conjugate with biotinmodulated anti-EGFR antibody. The resultant probes were characterized for their particle size, surface potential and structural integrity with dynamic light scattering (DLS), Zetasizer, and transmission electronic microscopy (TEM), respectively. In-vitro targeting specificity of the probe was evaluated with fluorescence microscopy by comparing the binding capacity of a fluorescence-labeled probe in a human head and neck cancer cell line, 15B (high EGFR overexpression) and a human embryonic kidney cell line, HEK293 (low EGFR control). The subsequent cytotoxicity toward these two cell lines was quantified by MTT assay. Finally, the in vitro applicability of MRI contrast Gd within the probe was demonstrated by detecting cellbound particles with MR imaging. Results: Using TEM scanning, our probe was observed to be spherical in shape and identical in particle size, approximately 100nm. The surface potential was +5.13mV. The EGFR-specific targeting assay with fluorescence-labeled probes showed significantly high occupancy of the probe on the surface of 15B cells in comparison with HEK293 cells. Furthermore, the T1 relaxation time of this EGFR-specific probe attached to15B cells was measured to be 379.3 ms, shorter than that of control vector without anti-EGFR conjugation (516.2 ms). Conclusion: We have demonstrate targeting specificity of a multi-functional nanoprobe in discriminating high and low EGFR-expressing cells. The incorporation of MRI contrast Gd successfully revealed the cell-targeted probe under MR imaging. These results suggest that this probe can function as a targeting tracer for tumor cells, potentiating it in improving treatment efficacy through MR imaging. Author Disclosure: Y. Kuo: None. C. Hung: None. S.R. Raghavan: None. W.D. D’Souza: None.

Using the neurotransmitter serotonin to target imaging agents to glioblastoma cells

The neurotransmitter serotonin is involved in numerous bodily functions via seven different serotonin receptor subfamilies. Serotonin plays a role in gastrointestinal functions like intestinal secretion or peristalsis and neuropsychiatric events like depression or migraine. One of these subtypes has been found on glioblastoma cells, inducing growth promotion. In our study we attempted to target imaging agents to glioblastoma cells via the serotonin receptor. For this we coupled serotonin to the fluorescent dye rhodamine and the magnetic resonance imaging contrast agent gadolinium (Gd)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). The cellular uptake, cytotoxicity and detection sensitivity of the conjugates were evaluated by confocal laser scanning microscopy (CLSM), cell growth analysis, flow cytometry and magnetic resonance relaxometry on U373 human glioblastoma cells. Receptor-dependency of the uptake was confirmed by competition experiments with excess of unmarked serotonin. Cellular uptake of the conjugates was found in CLSM, magnetic resonance relaxometry and flow cytometry experiments.CLSM revealed the cytoplasmic character of the uptake. In cell growth analysis experiments no adverse effect of either conjugate on the cells was observed. Competition experiments performed with the conjugates and unmarked serotonin showed decreased conjugate uptake compared to the experiments without competition. In conclusion the neurotransmitter serotonin could be successfully used to target imaging agents into human glioblastoma cells. This makes it of interest for future glioblastoma imaging methods.

A magnetic resonance imaging contrast agent differentiates between the vascular properties of fetal striatal tissue transplants and gliomas in rat brain in vivo

The tumors formed by rat C-6 glioma cells were isointense with the normal rat brain on precontrast T 1 weighted magnetic resonance (MR) images. Following i.v. peripheral administration of the MR imaging contrast agent gadolinium (Gd)-DTPA, there was no significant change in the signal intensity from normal brain tissue. However, the tumor appeared as areas of high signal intensity demonstrating the abnormal vascular properties of the tumor. Fetal rat striatal tissue transplanted into unlesioned adult rat striatum appeared isointense with the host brain on precontrast T 1 weighted images and there was no evidence for enhancement of the transplanted tissue relative to host brain following i.v. administration of Gd-DTPA. Using this technique we found no evidence with respect to permeability of the contrast agent of an abnormal blood-brain barrier within the striatal transplant in vivo.

Use of Gd-DTPA and fast gradient-echo and spin-echo MR imaging to demonstrate renal function in the rabbit.

The paramagnetic magnetic resonance (MR) imaging contrast agent gadolinium diethylenetriaminepentaacetic acid (DTPA) is freely filtered at the glomerulus and is neither secreted nor reabsorbed by the renal tubules. Fast MR imaging techniques, either gradient-echo or spin-echo, can be used to document the passage of Gd-DTPA through the renal tubules, as reflected by alteration in the MR signal intensity within the different anatomic regions of the kidney. Gradient-echo (repetition time of 35 msec, echo time of 7 msec, flip angles of 10 degrees-100 degrees) and spin-echo (repetition time of 35 msec, echo time of 8 msec) pulse sequences were used to acquire 20 consecutive images, one every 12 seconds, of the rabbit kidney. Both pulse sequences depicted the time course of Gd-DTPA distribution through the kidney but with distinctly different patterns of MR signal change. These dynamic MR images provide an MR nephrogram that directly demonstrates renal morphology and indirectly reflects the functional status of the renal vasculature, renal perfusion, and tubular concentrating ability.