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Synthesis and characterization of new low‐molecular‐weight lysine‐conjugated Gd‐DTPA contrast agents
Sophie Laurent Carmen Burtea Luce Vander Elst Robert N. Muller 《CONTRAST MEDIA & MOLECULAR IMAGING》2011,6(4):229-235
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
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Paolo Ricci MD Vito Cantisani MD PhD Mirko D'Onofrio MD Dushyant Sahani MD Elisa Pagliara MD Fabrizio Calliada MD Erturk Mehmet MD Kalva Sanjeva MD Nicola Faccioli MD Roberto Pozzi-Mucelli MD Ugo D'Ambrosio MD Roberto Passariello MD 《Journal of ultrasound in medicine》2008,27(12):1719-1726
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
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Comparison of contrast‐enhanced ultrasonograpy with Gd‐EOB‐DTPA‐enhanced MRI in the diagnosis of liver metastasis from colorectal cancer
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Kazue Shiozawa MD PhD Manabu Watanabe MD PhD Takashi Ikehara MD PhD Yasushi Matsukiyo MD Michio Kogame MD Yoshinori Kikuchi MD PhD Yuichiro Otsuka MD PhD Hironori Kaneko MD PhD Yoshinori Igarashi MD PhD Yasukiyo Sumino MD PhD 《Journal of clinical ultrasound : JCU》2017,45(3):138-144
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Contrast‐enhanced sonography for the identification of benign and malignant thyroid nodules: Systematic review and meta‐analysis
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Xuelei Ma MD Binglan Zhang MD Wenwu Ling MD Rongjun Liu MS Hongyuan Jia MD Fuping Zhu MD Mengyao Wang PhD Haoqiu Liu PhD Jingwen Huang MD Lei Liu MD 《Journal of clinical ultrasound : JCU》2016,44(4):199-209
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Three‐dimensional imaging of the mouse heart and vasculature using micro‐CT and whole‐body perfusion of iodine or phosphotungstic acid
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P. Joy Dunmore‐Buyze Elsbeth Tate Fu‐li Xiang Sarah A. Detombe Zengxuan Nong J. Geoffrey Pickering Maria Drangova 《CONTRAST MEDIA & MOLECULAR IMAGING》2014,9(5):383-390
Recent studies have investigated histological staining compounds as micro‐computed tomography (micro‐CT) contrast agents, delivered by soaking tissue specimens in stain and relying on passive diffusion for agent uptake. This study describes a perfusion approach using iodine or phosphotungstic acid (PTA) stains, delivered to an intact mouse, to capitalize on the microvasculature as a delivery conduit for parenchymal staining and direct contact for staining artery walls. Twelve C57BL/6 mice, arterially perfused with either 25% Lugol's solution or 5% PTA solution were scanned intact and reconstructed with 26 µm isotropic voxels. The animals were fixed and the heart and surrounding vessels were excised, embedded and scanned; isolated heart images were reconstructed with 13 µm isotropic voxels. Myocardial enhancement and artery diameters were measured. Both stains successfully enhanced the myocardium and vessel walls. Interestingly, Lugol's solution provided a significantly higher enhancement of the myocardium than PTA [2502 ± 437 vs 656 ± 178 Hounsfield units (HU); p < 0.0001], delineating myofiber architecture and orientation. There was no significant difference in vessel wall enhancement (Lugol's, 1036 ± 635 HU; PTA, 738 ± 124 HU; p = 0.29), but coronary arteries were more effectively segmented from the PTA‐stained hearts, enabling segmented imaging of fifth‐ order coronary artery branches. The combination of whole mouse perfusion delivery and use of heavy metal‐containing stains affords high‐resolution imaging of the mouse heart and vasculature by micro‐CT. The differential imaging patterns of Lugol's‐ and PTA‐stained tissues reveals new opportunities for micro‐analyses of cardiac and vascular tissues. Copyright © 2014 John Wiley & Sons, Ltd. 相似文献
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Jeanne S. Chow Harriet J. Paltiel Horacio M. Padua Erin McNamara Belinda H. Dickie 《Journal of ultrasound in medicine》2019,38(10):2777-2783
This case series describes a novel method for showing the preoperative anatomy of children with anorectal malformations using ultrasound contrast, which we have termed “contrast‐enhanced colosonography (ceCS).” Six patients with anorectal malformations without a perineal fistula were studied both by fluoroscopic distal colostography and ceCS, and their results were confirmed surgically. Contrast‐enhanced CS precisely showed the complex anatomic relationships in all cases. Compared to traditional fluoroscopic studies, ceCS has the benefit of no associated ionizing radiation and thus is safer for children. 相似文献
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Hans‐Jürgen Raatschen Rebecca Swain David M. Shames Yanjun Fu Zachary Boyd Matthew L. Zierhut Michael F. Wendland Bernd Misselwitz Hanns‐Joachim Weinmann Karl‐Jürgen Wolf Robert C. Brasch 《CONTRAST MEDIA & MOLECULAR IMAGING》2006,1(3):113-120
The rationale and objectives were to define the MRI tumor‐characterizing potential of a new protein‐avid contrast agent, Gd‐GlyMe‐DOTA‐perfluorooctyl‐mannose‐conjugate (Gadofluorine M?; Schering AG, Berlin, Germany) in a chemically induced tumor model of varying malignancy. Because of the tendency for this agent to form large micelles in water and to bind strongly to hydrophobic sites on proteins, it was hypothesized that patterns of dynamic tumor enhancement could be used to differentiate benign from malignant lesions, to grade the severity of malignancies and to define areas of tumor necrosis. Gadofluorine M, 0.05 mmol Gd kg?1, was administered intravenously to 28 anesthetized rats that had developed over 10 months mammary tumors of varying degrees of malignancy as a consequence of intraperitoneal administration of N‐ethyl‐N‐nitrosourea (ENU), 45–250 mg kg?1. These tumors ranged histologically from benign fibroadenomas to highly undifferentiated adenocarcinomas. Dynamic enhancement data were analyzed kinetically using a two‐compartment tumor model to generate estimates of fractional plasma volume (fPV), apparent fractional extracellular volume (fEV*) and an endothelial transfer coefficient (KPS) for this contrast agent. Tumors were examined microscopically for tumor type, degree of malignancy (Scarff–Bloom–Richardson score) and location of necrosis. Eighteen tumor‐bearing rats were successfully imaged. MRI data showed an immediate strong and gradually increasing tumor enhancement. KPS and fEV*, but not fPV obtained from tumors correlated significantly (p < 0.05) with the SBR tumor grade, r = 0.65 and 0.56, respectively. Estimates for KPS and fEV* but not fPV were significantly lower in a group consisting of benign and low‐grade malignant tumors compared with the group of less‐differentiated high‐grade tumors (1.61 ± 0.64 vs 3.37 ± 1.49, p < 0.01; 0.45 ± 0.17 vs 0.78 ± 0.24, p < 0.01; and 0.076 ± 0.048 vs 0.121 ± 0.088, p = 0.24, respectively). It is concluded that the protein‐avid MRI contrast agent Gadofluorine M enhances tumors of varying malignancy depending on the tumor grade, higher contrast agent accumulation for more malignant lesions. The results show potential utility for differentiating benign and low‐grade malignant lesions from high‐grade cancers. Copyright © 2006 John Wiley & Sons, Ltd. 相似文献
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M. Almajdub M. Nejjari G. Poncet L. Magnier E. Chereul C. Roche M. Janier 《CONTRAST MEDIA & MOLECULAR IMAGING》2007,2(2):88-93
The present study sought to validate the use of glycery1‐2‐oley‐1,3‐bis‐[7‐(3‐amino‐2,4,6‐triiodophenyl)‐ heptanoate] (DHOG) contrast agent for mouse spleen tumor and liver metastasis imaging by high‐resolution X‐ray microtomography. Three groups of female nude mice were compared: controls (n = 5), and mice injected with 2.5 × 106 STC1 tumor cells in the spleen, imaged at 15 days (group G15, n = 5) and at 30 days (group G30, n = 5, of which one died before imaging). Micro‐CT scans (X‐ray voltage, 50 kVp; anode current, 200 µA; exposure time, 632 ms; 180 rotational steps resulting in 35 µm isotropic spatial resolution) were acquired at 0, 0.75, 2 and 4 h after i.v. injection of DHOG. CT number (Hounsfield units: HU) and contrast‐to‐noise ratios (CNR) were determined in three organs. Statistical analysis was performed by Mann–Whitney U‐test. Contrast enhancement in normal spleen and liver increased, respectively to 1020 ± 159 and 351 ± 27 HU over baseline at 4 h, and 482 ± 3 and 203 ± 14 HU on day 6 after a single contrast injection. Automated three‐dimensional reconstruction and modeling of the spleen provided accurate and quantifiable images. Spleen tumor and liver metastases did not take up DHOG, making them detectable in contrast to the increased signal in normal tissue. The smallest liver metastasis detected measured 0.3 mm in diameter. High‐resolution X‐ray micro‐CT in living mice using DHOG contrast agent allowed visualization and volume quantification of normal spleen and of spleen tumor and its liver metastases. Copyright © 2007 John Wiley & Sons, Ltd. 相似文献
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H. M. H. F. Sanders G. J. Strijkers W. J. M. Mulder H. P. Huinink S. J. F. Erich O. C. G. Adan N. A. J. M. Sommerdijk M. Merkx K. Nicolay 《CONTRAST MEDIA & MOLECULAR IMAGING》2009,4(2):81-88
Collagen is an important component of the extracellular matrix (ECM) and plays an important role in normal tissue maturation and in pathological processes such as atherosclerosis and myocardial infarction. The diagnostics of the latter diseases using MRI could strongly benefit from the use of collagen‐specific contrast agents. The current study aimed to develop a bimodal liposomal MR contrast agent that was functionalized with CNA35, a collagen adhesion protein of the Staphylococcus aureus bacterium. The liposomes were characterized in terms of CNA35 protein conjugation and loading. The overall morphology was assessed with DLS and cryo‐TEM, while cryo‐TEM tomography was used to visualize the protein coverage of the liposomes. The binding properties of the contrast agent were investigated using a fluorescence assay based on the rhodamine content of the liposomes. The bulk relaxivity was determined using regular relaxometry while the MR‐properties of liposomes in their bound state were studied using NMR depth profiling. This CNA35 functionalized contrast agent and the set of in vitro experiments we performed indicate the potential of this technology for in vivo molecular imaging of collagen. Copyright © 2009 John Wiley & Sons, Ltd. 相似文献
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Andrea Kassner Rebecca E. Thornhill Fang Liu Patrick M. Winter Shelton D. Caruthers Samuel A. Wickline Gregory M. Lanza 《CONTRAST MEDIA & MOLECULAR IMAGING》2010,5(3):155-161
The purpose of this study was to evaluate the suitability of a macromolecular MRI contrast agent (paramagnetic nanoparticles, PNs) for the characterization of tumor angiogenesis. Our aim was to estimate the permeability of PNs in developing tumor vasculature and compare it with that of a low molecular weight contrast agent (Gd‐DTPA) using dynamic contrast‐enhanced MRI (DCE). Male New Zealand white rabbits (n = 5) underwent DCE MRI 12–14 days after Vx‐2 tumor fragments were implanted into the left hind limb. Each contrast agent (PNs followed by Gd‐DTPA) was evaluated using a DCE protocol and transendothelial transfer coefficient (Ki) maps were calculated using a two‐compartment model. Two regions of interest (ROIs) were located within the tumor core and hindlimb muscle and five ROIs were placed within the tumor rim. Comparisons were performed using repeated measures analysis of variance (ANOVA). The Ki values estimated using PNs were significantly lower than those obtained for Gd‐DTPA (p = 0.018). When PNs and Gd‐DTPA data were analyzed separately, significant differences were identified among tumor rim ROIs for PNs (p < 0.0001), but not for Gd‐DTPA data (p = 0.34). The mean Ki for the tumor rim was significantly greater than that of either the core or the hindlimb muscle for both contrast agents (p < 0.05 for each comparison). In summary, the extravasation of Gd‐DTPA was far greater than that of PNs, suggesting that PNs can reveal regional differences in tumor vascular permeability that are not otherwise apparent with clinical contrast agents such as Gd‐DTPA. These results suggest that PNs show potential for the noninvasive delineation of tumor angiogenesis. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献