首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 15 毫秒
1.
2.
Various blood pool contrast agents (CAs), characterized by intravascular distribution, have been developed to assist contrast enhanced magnetic resonance angiography (MRA). Among these CAs, the DTPA derivatives conjugated to synthetic polypeptides, such as polylysine, represent attractive candidates for blood pool imaging. However, due to the presence of charged residues located on their backbone, these agents are retained in the kidneys and this compromises their long blood half‐life. In order to overcome this major drawback of the polylysine compounds, two new low‐molecular‐weight CAs were synthesized in the present work by conjugating four or six 1‐p‐isothiocyanatobenzyl‐DTPA moieties to tri‐ or penta‐Lys peptides [(Gd‐DTPA)4Lys3 and (Gd‐DTPA)6Lys5], respectively. All the –NH2 groups of Lys were thus blocked by covalent conjugation to DTPA. The stability and relaxometric properties of these compounds, as well as their pharmacokinetic and biodistribution characteristics, were then evaluated. The half‐life in blood of these new polylysine derivatives, as determined in rats, is twofold longer than that of Gd‐DTPA. The compounds could thus be optimal blood pool markers for MRA, which typically uses fast acquisition times. The absence of positive molecular charge did not limit their retention in kidneys 2 h after administration. On the other hand, (Gd‐DTPA)4Lys3 is retained in kidneys to a lesser extent than (Gd‐DTPA)6Lys5. Their moderate retention in blood and their higher stability and relaxivity in comparison with Gd‐DTPA highlight these polylysine derivatives as optimal compared with previously developed polylysine compounds. Copyright © 2010 John Wiley & Sons, Ltd.  相似文献   

3.
4.
5.
6.
7.
Chemical exchange saturation transfer (CEST) MRI is sensitive to dilute labile protons and microenvironmental properties, augmenting routine relaxation‐based MRI. Recent developments of quantitative CEST (qCEST) analysis such as omega plots and RF‐power based ratiometric calculation have extended our ability to elucidate the underlying CEST system beyond the simplistic apparent CEST measurement. CEST MRI strongly varies with experimental factors, including the RF irradiation level and duration as well as repetition time and flip angle. In addition, the CEST MRI effect is typically small, and experimental optimization strategies have to be carefully evaluated in order to enhance the CEST imaging sensitivity. Although routine CEST MRI has been optimized largely based on maximizing the magnitude of the CEST effect, the CEST signal‐to‐noise (SNR) efficiency provides a more suitable optimization index, particularly when the scan time is constrained. Herein, we derive an analytical solution of the CEST effect that takes into account key experimental parameters including repetition time, imaging flip angle and RF irradiation level, and solve its SNR efficiency. The solution expedites CEST imaging sensitivity calculation, substantially faster than the Bloch–McConnell equation‐based numerical simulation approach. In addition, the analytical solution‐based SNR formula enables the exhaustive optimization of CEST MRI, which simultaneously predicts multiple optimal parameters such as repetition time, flip angle and RF saturation level based on the chemical shift and exchange rate. The sensitivity efficiency‐based optimization approach could simplify and guide imaging of CEST agents, including glycogen, glucose, creatine, gamma‐aminobutyric acid and glutamate. Copyright © 2016 John Wiley & Sons, Ltd.  相似文献   

8.
9.
Objective. The purpose of this study was to describe the behavior of histologically proven hepatocellular adenoma (HCA) on low‐mechanical index (MI) contrast‐enhanced ultrasonography (CEUS). Methods. A review of the databases from 4 academic hospitals revealed 18 patients (15 female and 3 male; mean age, 40 years; range, 25–71 years) with 25 histologically proven HCA lesions who were studied with CEUS at a low MI (0.04–0.1). Results. Twenty‐four of 25 lesions (96%; 95% confidence interval [CI], 80.5%–99.3%) showed high‐intensity enhancement, scored as 3 on a scale of 0 to 3, whereas only 1 lesion (4%; 95% CI, 0.7%–19.5%) was scored as 2. The time of peak enhancement ranged between 10 and 19 seconds (average, 13 seconds). All but 1 of the 25 lesions (96%; 95% CI, 80.5%–99.3%) showed early homogeneous and centripetal enhancement during the hepatic arterial phase. No portal venous phase enhancement was observed in any lesion because all showed rapid wash‐out (100%; 95% CI, 86.7%–100%). Twenty lesions (80%; 95% CI, 60.9%–91.1%) were found to be isoechoic to slightly hypoechoic during the portal phase, and 19 (76%; 95% CI, 56.6%–88.5%) were isoechoic to mildly hypoechoic, whereas 7 (24%; 95% CI, 11.5%–43.4%) were hypoechoic during the late phase. Conclusions. Contrast‐enhanced ultrasonography is an effective technique for identifying the microvascular and macrovascular characteristics of HCA. Typically, HCA shows early (10–19 seconds) and centripetal enhancement during the arterial phase and isoechogenicity or mild hypoechogenicity during the portal phase, remaining slightly hypoechoic or isoechoic during the late phase in most cases.  相似文献   

10.
Among all the diagnostic imaging modalities, X‐ray imaging techniques are the most commonly used owing to their high resolution and low cost. The improvement of these techniques relies heavily on the development of novel X‐ray contrast agents, which are molecules that enhance the visibility of internal structures within the body in X‐ray imaging. To date, clinically used X‐ray contrast agents consist mainly of small iodinated molecules that might cause severe adverse effects (e.g. allergies, cardiovascular diseases and nephrotoxicity) in some patients owing to the large and repeated doses that are required to achieve good contrast. For this reason, there is an increasing interest in the development of alternative X‐ray contrast agents utilizing elements with high atomic numbers (e.g. gold, bismuth, ytterbium and tantalum), which are well known for exhibiting high absorption of X‐rays. Nanoparticles (NPs) made from these elements have been reported to have better imaging properties, longer blood circulation times and lower toxicity than conventional iodinated X‐ray contrast agents. Additionally, the combination of two or more of these elements into a single carrier allows for the development of multimodal and hybrid contrast agents. Herein, the limitations of iodinated X‐ray contrast agents are discussed and the parameters that influence the efficacy of X‐ray contrast agents are summarized. Several examples of the design and production of both iodinated and iodine‐free NP‐based X‐ray contrast agents are then provided, emphasizing the studies performed to evaluate their X‐ray attenuation capabilities and their toxicity in vitro and in vivo. Copyright © 2014 John Wiley & Sons, Ltd.  相似文献   

11.
12.
The purpose of this study was to compare contrast and image quality of whole‐body equilibrium‐phase high‐spatial‐resolution MR angiography using a non‐protein‐binding unspecific extracellular gadolinium‐based contrast medium with that of two contrast media with different protein‐binding properties. 45 patients were examined using either 15 mL of gadobutrol (non‐protein‐binding, n = 15), 32 mL of gadobenate dimeglumine (weakly protein binding, n = 15) or 11 mL gadofosveset trisodium (protein binding, n = 15) followed by equilibrium‐phase high‐spatial‐resolution MR‐angiography of four consecutive anatomic regions. The time elapsed between the contrast injection and the beginning of the equilibrium‐phase image acquisition in the respective region was measured and was up to 21 min. Signal intensity was measured in two vessels per region and in muscle tissue. Relative contrast (RC) values were calculated. Vessel contrast, artifacts and image quality were rated by two radiologists in consensus on a five‐point scale. Compared with gadobutrol, gadofosveset trisodium revealed significantly higher RC values only when acquired later than 15 min after bolus injection. Otherwise, no significant differences between the three contrast media were found regarding vascular contrast and image quality. Equilibrium‐phase high‐spatial‐resolution MR‐angiography using a weakly protein‐binding or even non‐protein‐binding contrast medium is equivalent to using a stronger protein‐binding contrast medium when image acquisition is within the first 15 min after contrast injection, and allows depiction of the vasculature with high contrast and image quality. The protein‐binding contrast medium was superior for imaging only later than 15 min after contrast medium injection. Copyright © 2015 John Wiley & Sons, Ltd.  相似文献   

13.
14.
The binding interaction of metal chelates to biological macromolecules, though driven by properly devoted recognition synthons, may cause dramatic changes in some property associated with the coordination cage such as the thermodynamic stability or the exchange rate of the metal coordinated water. Such changes are due to electrostatic and H‐bonding interactions involving atoms of the coordination cage and atoms of the biological molecule at the binding site. To mimic this type of H‐bonding interactions, lanthanide(III) complexes with a DTPA–monophosphonate ligand bearing a propylamino moiety (H6NP–DTPA) were synthesized. Their thermodynamic stabilities and the exchange lifetime of the coordinated water molecule (for the Gd‐complex) were compared with those of the analog complexes with DTPA and the parent DTPA–monophosphonate derivative (H6P–DTPA). It was found that the intramolecular H‐bond between the ε‐amino group and the phosphonate moiety in NP–DTPA complexes causes displacements of electric charges in their coordination cage that are markedly pH dependent. In turn, this affects the characteristic properties of the coordination cage. In particular it results in a marked elongation of the exchange lifetime of the coordinated water molecule. Copyright © 2007 John Wiley & Sons, Ltd.  相似文献   

15.
16.
A novel conjugate of phenylboronic acid and an Ln(DTPA) derivative, in which the central acetate pendant arm was replaced by the methylamide of L ‐lysine, was synthesized and characterized. The results of a fit of variable 17O NMR data and a 1H NMRD profile show that the water residence lifetime of the Gd(III) complex (150 ns) is shorter than that of the parent compound Gd(DTPA)2? (303 ns). Furthermore, the data suggest that several water molecules in the second coordination sphere of Gd(III) contribute to the relaxivity of the conjugate. The Ln(III) complexes of this conjugate are highly suitable for molecular recognition of sugars. The interaction with various sugars was investigated by 11B NMR spectroscopy. Thanks to the thiourea function that links the phenylboronic acid targeting vector with the DTPA derivative, the interactions are stronger than that of phenylboronic acid itself. In particular, the interaction with N‐propylfructosamine, a model for the glucose residue in glycated human serum albumin (HSA), is very strong. Unfortunately, the complex also shows a rather strong interaction with hexose‐free HSA (KA = 705 ± 300). Copyright © 2007 John Wiley & Sons, Ltd.  相似文献   

17.
Prior to imaging agent use in preclinical studies and clinical diagnostics, biological activity must be validated. The Lindmo assay has been used conventionally to quantify radiolabeled antibody (Ab) immunoreactivity, although published findings suggest it does not provide consistently accurate results. We developed and tested a near‐infrared (NIR) flow cytometry (FC) method for quantifying biological activity of a dual‐labeled Ab for use as a multimodal contrast agent in small animal and human positron emission tomography and NIR fluorescence imaging. Antibody specific for epithelial cell adhesion molecule was conjugated to DOTA–NHS–ester, labeled with IRDye 800CW and further labeled with 64Cu or nonradioactive Cu prior to reacting with human prostate cancer cells for testing by the Lindmo or FC method, respectively. Immunoreactivity of the dual‐labeled agent was found to be 76.4 ± 15.7% by the Lindmo assay. When tested with and without Cu labeling using NIR FC, the biological activity was found to be 73.1 ± 7.7 and 79.4 ± 8.1%, respectively. No significant differences were found between these activity levels (p > 0.05), supporting NIR FC as an alternative method for measuring immunoreactivity and demonstrating that Cu labeling does not significantly affect the agent's ability to bind to its target. Biological activity was significantly reduced when the NIR dye‐to‐protein ratio was increased 3‐ to 4‐fold in agent preparations when tested by FC and the Lindmo assay. In summary, NIR FC is an alternative with similar specificity and sensitivity, and greater reproducibility relative to the Lindmo assay for quantifying biological activity of NIR fluorophore‐labeled, multimodal imaging agents. Copyright © 2012 John Wiley & Sons, Ltd.  相似文献   

18.
Biocompatible polymeric encapsulants have been widely used as a delivery vehicle for a variety of drugs and imaging agents. In this study, X‐ray contrast agent (iopamidol) is encapsulated into a polymeric microparticle (polyvinyl alcohol) as a particulate flow tracer in synchrotron X‐ray imaging system. The physical properties of the designed microparticles are investigated and correlated with enhancement in the imaging efficiency by experimental observation and theoretical interpretation. The X‐ray absorption ability of the designed microparticle is assessed by Beer–Lambert–Bouguer law. Particle size, either in dried state or in solvent, primarily dominates the X‐ray absorption ability under the given condition, thus affecting imaging efficiency of the designed X‐ray contrast flow tracers. Copyright © 2011 John Wiley & Sons, Ltd.  相似文献   

19.
20.
Reliable methods of imaging myelin are essential to investigate the causes of demyelination and to study drugs that promote remyelination. Myelin‐specific compounds can be developed into imaging probes to detect myelin with various imaging techniques. The development of multimodal myelin‐specific imaging probes enables the use of orthogonal imaging techniques to accurately visualize myelin content and validate experimental results. Here, we describe the synthesis and application of multimodal myelin‐specific imaging agents for light microscopy and magnetic resonance imaging. The imaging agents were synthesized by incorporating the structural features of luxol fast blue MBS, a myelin‐specific histological stain, into texaphyrins coordinated to GdIII. These new complexes demonstrated absorption of visible light, emission of near‐IR light, and relaxivity values greater than clinically approved contrast agents for magnetic resonance imaging. These properties enable the use of optical imaging and magnetic resonance imaging for visualization of myelin. We performed section‐ and en block‐staining of ex vivo mouse brains to investigate the specificity for myelin of the new compounds. Images obtained from light microscopy and magnetic resonance imaging demonstrate that our complexes are retained in white matter structures and enable detection of myelin. Copyright © 2016 John Wiley & Sons, Ltd.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号