The gadolinium complexes with polyoxometalates as potential MRI contrast agents

The two gadolinium (Gd) polyoxometalates, K(15)[Gd(BW(11)O(39))(2)] [Gd(BW(11))(2)] and K(17)[Gd(CuW(11)O(39))(2)] [Gd(CuW(11))(2)] have been evaluated by in vivo and in vitro experiments as the candidates of potential tissue-specific magnetic resonance imaging (MRI) contrast agents. T(1) relaxivities of 17.12 mM(-1) x s(-1) for Gd(BW(11))(2) and 19.95 mM(-1) x s(-1) for Gd(CuW(11))(2) (400 MHz, 25 degrees C) were much higher than that of the commercial MRI contrast agent (GdDTPA). Their relaxivities in bovine serum albumin and human serum transferrin solutions were also reported. After administration of Gd(BW(11))(2) and Gd(CuW(11))(2) to Wistar rats, MRI showed longer and remarkable enhancement in rat liver and favorable renal excretion capability. The signal intensity increased by 37.63+/-3.45% for the liver during the whole imaging period (100 min) and by 61.47+/-10.03% for kidney within 5-40 min after injection at 40+/-1-micromol x kg(-1) dose for Gd(CuW(11))(2), and Gd(BW(11))(2) induced 50.44+/-3.51% enhancement in the liver in 5-50-min range and 61.47+/-10.03% enhancement for kidney within 5-40 min after injection at 39+/-4 micromol x kg(-1) dose. In vitro and in vivo study showed that Gd(BW(11))(2) and Gd(CuW(11))(2) are favorable candidates as tissue-specific contrast agents for MRI.     

Investigation of sandwiched gadolinium (III) complexes with tungstosilicates as potential MRI contrast agents

Two gadolinium-sandwiched complexes with tungstosilicates, K(13)[Gd(SiW(11)O(39))(2)] (Gd(SiW(11))(2)) and K(11)H(6)[Gd(3)O(3)(SiW(9)O(34))(2)] (Gd(3)(SiW(9))(2)), have been investigated by in vitro and in vivo experiments as potential contrast agents for magnetic resonance imaging (MRI). T(1)-relaxivity of Gd(SiW(11))(2)was 6.59 mM(-1).s(-1) in aqueous solution and 6.85 mM(-1).s(-1) in 0.725 mmol.L(-1) bovine serum albumin solution at 25 degrees C and 9.39 T, respectively. The corresponding T(1)-relaxivity of Gd(3)(SiW(9))(2) was 12.6 and 19.3 mM(-1).s(-1) per Gd, respectively. MRI for Sprague-Dawley rats showed longer and more remarkable enhancement in rat liver after i.v. injection of these two complexes: 39.4 +/- 3.9% and 57.4 +/- 11.6% within the first 30 min after injection, 31.2 +/- 2.6% and 39.9 +/- 7.6% in the next 60 min for Gd(SiW(11))(2) and Gd(3)(SiW(9))(2) at doses of 0.081 and 0.084 mmol Gd/kg, respectively. Our preliminary in vitro and in vivo study indicates that Gd(SiW(11))(2) and Gd(3)(SiW(9))(2) are favorable candidates for hepatic contrast agents for MRI. However, the two complexes exhibit higher acute toxicity and need to be modified and studied further before clinical use.     

Structural effect on degradability and in vivo contrast enhancement of polydisulfide Gd(III) complexes as biodegradable macromolecular MRI contrast agents

The structural effect of biodegradable macromolecular magnetic resonance imaging (MRI) contrast agents, polydisulfide gadolinium (Gd)(III) chelates, on their in vitro degradability, and cardiovascular and tumor imaging were evaluated in mice. Polydisulfide Gd(III) chelates, Gd-DTPA cystamine copolymers (GDCC), Gd-DTPA l-cystine copolymers (GDCP), Gd-DTPA d-cystine copolymers (dGDCP) and Gd-DTPA glutathione (oxidized) copolymers (GDGP), with different sizes and narrow molecular weight distribution were prepared and evaluated both in vitro and in vivo in mice bearing MDA-MB-231 tumor xenografts. GDGP with large steric hindrance around the disulfide bonds had greater T(1) and T(2) relaxivities than GDCC, GDCP and dGDCP. The degradability of the polydisulfide by the endogenous thiols decreased with increasing steric effects around the disulfide bonds in the order of GDCC>GDCP, dGDCP>GDGP. The size and degradability of the contrast agents had a significant impact on vascular contrast enhancement kinetics. The agents with a large size and low degradability resulted in more prolonged vascular enhancement than the agents with a small size and high degradability. It seems that the size and degradability of the agents did not significantly affect tumor enhancement. All agents resulted in significant contrast enhancement in tumor tissue. This study has demonstrated that the vascular enhancement kinetics of the polydisulfide MRI contrast agents can be controlled by their sizes and structures. The polydisulfide Gd(III) chelates are promising biodegradable macromolecular MRI contrast agents for magnetic resonance angiography and cancer imaging.     

Relaxivity of Gd-based contrast agents on X nuclei with long intrinsic relaxation times in aqueous solutions

The relaxivity of commercially available gadolinium (Gd)-based contrast agents was studied for X-nuclei resonances with long intrinsic relaxation times ranging from 6 s to several hundred seconds. Omniscan in pure 13C formic acid had a relaxivity of 2.9 mM(-1) s(-1), whereas its relaxivity on glutamate C1 and C5 in aqueous solution was approximately 0.5 mM(-1) s(-1). Both relaxivities allow the preparation of solutions with a predetermined short T1 and suggest that in vitro substantial sensitivity gains in their measurement can be achieved. 6Li has a long intrinsic relaxation time, on the order of several minutes, which was strongly affected by the contrast agents. Relaxivity ranged from approximately 0.1 mM(-1) s(-1) for Omniscan to 0.3 for Magnevist, whereas the relaxivity of Gd-DOTP was at 11 mM(-1) s(-1), which is two orders of magnitude higher. Overall, these experiments suggest that the presence of 0.1- to 10-microM contrast agents should be detectable, provided sufficient sensitivity is available, such as that afforded by hyperpolarization, recently introduced to in vivo imaging.     

氨基酸共聚物修饰的生物相容性MRI造影剂

通过天门冬氨酸(Asp)、异亮氨酸(Ile)热缩聚反应,制备了天门冬氨酸-异亮氨酸共聚物(AI),通过乙二胺(EDA)胺化,并与1,4,7,10-四氮杂环十二烷-1,4,7,10-四羧酸(DOTA)连接,再与钆离子(Gd3+)络合,合成了生物相容性大分子磁共振成像(MRI)造影剂——AI-EDA-DOTA-Gd.运用红外光谱(IR)、核磁共振(NMR)、电感耦合等离子谱(ICP)等方法对其进行结构表征,并通过弛豫性能、溶血性质、急性毒性及动物体内成像对其进行综合评价.体外弛豫结果表明,AI-EDA-DOTA-Gd的纵向弛豫效率(r_1=12.6mmol~(–1)×L×s~(–1))是商用造影剂Gd-DOTA(r_1=5.8 mmol~(–1)×L×s~(–1))的2.2倍.动物组织生理切片和溶血性实验结果说明其具有良好的生物相容性和较低的毒性.动物体内成像结果显示,AI-EDA-DOTA-Gd的最佳成像时间为30~70 min,注射AI-EDA-DOTA-Gd后的肝脏组织信号相比于未注射造影剂时增强了约(55.1±5.7)%.     

一种肝脏类生物相容性氨基酸共聚物磁共振成像造影剂

一种新型的以天门冬氨酸-苯丙氨酸共聚物为载体的大分子生物相容性材料(AP-EDA-DOTA-Gd)被制备出来作为磁共振成像造影剂．首先合成了天门冬氨酸-苯丙
氨酸共聚物,之后利用乙二胺将1,4,7,10-四氮杂环十二烷-1,4,7,10-四乙酸(DOTA)连接到共聚物上,最后将钆离子通过配位的作用方式连接到DOTA 上,最终得到大分子AP-EDA-DOTA-Gd．体外溶血性试验表明AP-EDA-DOTA-Gd 具有较好的血液相容性．在pH = 5.5 的组织蛋白酶B 的磷酸缓冲液中,AP-EDA-DOTA-Gd 能够降解．APEDA-DOTA-Gd 的体外弛豫效率(15.95 mmol^–1?L?s^–1)为目前临床应用的Gd-DOTA (5.59mmol^–1?L?s^–1)的2.9 倍．大鼠肝脏成像实验结果表明,AP-EDA-DOTA-Gd 对于肝组织的成像增强对比度为63.5±6.1%远高于Gd-DOTA (24.2±2.9%)．     

Biodegradable cystamine spacer facilitates the clearance of Gd(III) chelates in poly(glutamic acid) Gd-DO3A conjugates for contrast-enhanced MR imaging

Poly(L-glutamic acid) (PGA)-cystamine-[gadolinium (Gd)-DO3A] was prepared in high yield with a high Gd-DO3A conjugation efficiency. Approximately 55% of the carboxylic groups in PGA were loaded with Gd-DO3A via cystamine as the spacer. Cystamine can be readily cleaved by endogenous thiols to release the Gd(III) chelates from the conjugate facilitating Gd(III) excretion after the magnetic resonance imaging (MRI). The contrast-enhanced MRI with PGA-cystamine-(Gd-DO3A) was investigated in mice bearing MDA-MB-231 breast carcinoma xenografts. PGA-1,6-hexanediamine-(Gd-DO3A), a paramagnetic polymer conjugate of a nondegradable spacer, was used as a control. Both conjugates resulted in similar contrast enhancement in the heart, vasculature, liver and kidneys in the first hour post injection. More substantial signal intensity reduction was observed for PGA-cystamine-(Gd-DO3A) in these organs than PGA-1,6-hexanediamine-(Gd-DO3A) due to release of the Gd chelates from PGA-cystamine-(Gd-DO3A) after the cleavage of the disulfide spacer by the endogenous thiols. Both conjugates resulted in similar tumor enhancement with approximately 70% increased signal intensity in the tumor periphery and 10-40% increased signal intensity in tumor interstitium. No cross-reaction was observed between PGA-cystamine-(Gd-DO3A) and human serum albumin, a plasma protein containing a cysteine residue. PGA-cystamine-(Gd-DO3A) resulted in significantly lower Gd(III) tissue retention than PGA-1,6-hexanediamine-(Gd-DO3A) 10 days after the injection in the mice (P<.05). The conjugation of Gd(III) chelates to biomedical copolymers via the degradable disulfide spacer resulted in significant contrast enhancement in the blood pool and tumor tissue but minimal long-term Gd(III) tissue retention.     

The use of Gd DTPA as a perfusion agent and marker of blood-brain barrier disruption

To provide contrast enhancement in magnetic resonance imaging, a new class of compounds has been developed, the paramagnetic metal ion chelates. Gadolinium (Gd) DTPA, a prototype of this class, shows a sufficiently high in vivo stability and low toxicity for use in initial clinical trials. This type of agent, designed for rapid clearance by glomerular filtration, allows the assessment on MRI of renal function, alterations in tissue perfusion, myocardial ischemia, and perhaps most significantly disruption of the blood-brain barrier (BBB). Research at Vanderbilt has demonstrated these applications, with particular emphasis in three areas. Tissue perfusion changes, such as those produced by ligation of the arterial blood supply to portions of the spleen and kidney, cannot easily be detected on unenhanced MRI. These acute tissue infarcts can be readily identified following the administration of Gd DTPA. The question of field strength dependence of Gd DTPA has been addressed by experimentation at 0.15, 0.5, and 1.5 tesla. Furthermore, the ability to detect an alteration of the BBB, when present without associated edema, has been demonstrated with the application of control enhancement. The use of contrast agents in MRI will enhance both the sensitivity and specificity of magnetic resonance imaging.     

Evaluation of two new gadolinium chelates as contrast agents for MRI

Two new gadolinium chelates were investigated for potential use as tissue-specific contrast agents for magnetic resonance imaging. In vitro measurements of stability constants, octanol/water partition coefficients and relaxation times in solutions of water and human serum albumin (HSA) were performed with each new chelate and compared with gadolinium-diethylenetriamine pentaacetic acid, Gd(DTPA). Biodistribution studies and magnetic resonance imaging in rats were used to evaluate the new chelates in vivo. The stability constants (log K) of gadolinium-N,N″-bis(3-hydroxy-6-methyl-2-pyridylmethyl)diethylenetriamine-N,N′,N″-triacetic acid, Gd(DTTA-HP), and gadolinium-1,7-13-triaza-4,10-16-trioxacyclooctadecane-N,N′,N″-triacetic acid, Gd(TTCT), were determined to be 23.65 and 18.07, respectively. These can be compared to a literature value of 22.46 for Gd(DTPA). Octanol/water partition coefficients for both complexes showed they were more lipophilic than Gd(DTPA). Gd(DTTA-HP) exhibited a smaller relaxivity in water but a larger relaxivity in 4% HSA than Gd(DTPA). Gd(TTCT) exhibited a lower relaxivity than Gd(DTPA) in both water and 4% HSA. Both complexes showed similar biodistributions to Gd(DTPA) no carrier-added concentrations. Gd(DTTA-HP) had a greater percent change in signal intensity than Gd(DTPA) on T₁-weighted spin-echo images in the heart, liver, and kidney. Percent change in signal intensity for Gd(TTCT) was lower than Gd(DTPA) in heart, liver, and kidney.     

A comparison of T2*-weighted magnitude and phase imaging for measuring the arterial input function in the rat aorta following intravenous injection of gadolinium contrast agent

The arterial input function (AIF) is important for quantitative MR imaging perfusion experiments employing Gd contrast agents. This study compared the accuracy of T(2)*-weighted magnitude and phase imaging for noninvasive measurement of the AIF in the rat aorta. Twenty-eight in vivo experiments were performed involving simultaneous arterial blood sampling and MR imaging following Gd injection. In vitro experiments were also performed to confirm the in vivo results. At 1.89 T and TE=3 ms, the relationship between changes in 1/T(2)* in blood (estimated from MR signal magnitude) and Gd concentration ([Gd]) was measured to be approximately 19 s(-1) mM(-1), while that between phase and [Gd] was approximately 0.19 rad mM(-1). Both of these values are consistent with previously published results. The in vivo phase data had approximately half as much scatter with respect to [Gd] than the in vivo magnitude data (r(2)=.34 vs. r(2)=.17, respectively). This is likely due to the fact that the estimated change in 1/T(2)* is more sensitive than the phase to a variety of factors such as partial volume effects and T(1) weighting. Therefore, this study indicates that phase imaging may be a preferred method for measuring the AIF in the rat aorta compared to T(2)*-weighted magnitude imaging.     

Enhanced MRI of tumors utilizing a new nitroxyl spin label contrast agent

Nitroxyl spin labels have been shown to be effective in vivo contrast agents for magnetic resonance imaging (MRI) of the central nervous system, myocardium, and urinary tract. A new pyrrolidine nitroxyl contrast agent (PCA) with better resistance to in vivo metabolic inactivation than previously tested agents was studied for its potential to enhance subcutaneous neoplasms in an animal model. Twenty-two contrast enhancement trials were performed on a total of 15 animals 4-6 weeks after implantation with human renal adenocarcinoma. Spin echo imaging was performed using a .35 T animal imager before and after intravenous administration of PCA in doses ranging from 0.5 to 3mM/kg. The intensity of tumor tissue in the images increased an average of 35% in animals receiving a dose of 3 mM/kg. The average enhancement with smaller doses was proportionately less. Tumor intensity reached a maximum within 15 min of injection. The average intensity difference between tumor and adjacent skeletal muscle more than doubled following administration of 3 mM/kg of PCA. Well-perfused tumor tissue was more intensely enhanced than adjacent poorly perfused and necrotic tissue.     

An investigation of the toxicity of gadolinium based MRI contrast agents using neutron activation analysis

The toxicity of gadolinium (Gd) based MRI contrast agents, is based upon the amount of Gd that dissociates from its chelate and deposits in tissues. In this study, the toxicities of two contrast agents were tested using different injection strategies in two animal models. Following a bolus injection of 0.2 mmol/kg of Gd-DTPA in a pilot study with a single canine, Gd levels were as high as 2.05 +/- 0.17 ppm and 0.47 +/- 0.11 ppm 2 weeks post injection in the kidney and liver tissues, respectively. To evaluate the role that the injection strategy plays in toxicity, 0.8 mmol/kg of Gd-(HP-DO3A) was injected into rats, in a second study, via bolus and constant infusion techniques. Gd was only detected in the kidney in the bolus injected rats but in the lung as well in the constant infusion injected rats. Concentrations detected in the kidney for both strategies, were comparable within error: 1.37 +/- 0.46 ppm for the bolus and 1.24 +/- 0.39 ppm for the bolus/constant infusion strategy and 0.16 +/- 0.14 ppm in the lung for the constant infusion technique. The contrast infusion technique does not appear to present an increased risk of toxicity over the bolus technique except perhaps to a small degree in the lung.     

Reaction of gadolinium chelates with endogenously available ions

The extent of reaction of 153Gd-radiolabeled Gd(L) chelates with 25 mM CO23- (25 mF), PO34-, Zn2+ and Cu2+ at pH 7 was determined for L = EDTA, DTPA, DOTA, HP-DO3A, and DO3A. Gd(EDTA)- and Gd(DTPA)2- reacted (greater than 20% in 10 min) with Cu2+ and Zn2+ in the presence of PO34-. These double replacement reactions yielded precipitated GdPO4 and chelated Cu(L). Gd(HP-DO3A), Gd(DO3A) and Gd(DOTA)- were inert to reaction with all four ions at room temperature (less than or equal to 1% reaction detected). The thermodynamic binding constants of the ligands for Gd3+ and Cu2+ were found to be equal (10(20) M-1) for DO3A, while DOTA and HP-DO3A favored Gd3+ over Cu2+ by greater than or equal to 10(2) M-1. The low order of reactivity of Gd(DOTA)- and Gd(HP-DO3A) was anticipated by the binding constants, but the lack of reactivity of Gd(DO3A) is attributed to kinetic inertia. This latter property, desirable in MRI contrast agents, is promoted by the conformational stability of the tetraazacyclododecane macrocycle, which forms the backbone of the ligand. It is concluded that this class of chelates is exceptionally inert in solutions of endogenously available ions, and that thermodynamics alone is an insufficient predictor of the reactivity of the highly inert Gd complexes based on the tetraazamacrocycle.     

Gd complexes of diethylenetriaminepentaacetic acid conjugates of low-molecular-weight chitosan oligosaccharide as a new liver-specific MRI contrast agent

This study was to describe the synthesis of complexes of gadolinium diethylenetriaminepentaacetic acid conjugates of low-molecular-weight chitosan oligosaccharide Gd-DTPA-CSn (n = 6, 8, 11) as a new class of contrast agent as well as its magnetic property in a pilot magnetic resonance imaging. The efficacy of the contrast agent was assessed by measuring the longitudinal relaxivity (r₁), FLASH imaging in phantoms in vitro and signal intensity in vivo of the rat abdominal axial imaging. The r₁ of Gd-DTPA-CS₁₁ was up to 11.65 mM^− 1·s^− 1, which was 3 times higher than that of the analogous MRI contrast agent Gd-DTPA in commercial use. In vivo MR images of rat obtained with Gd-DTPA-CS₁₁ showed strong signal enhancement in liver and the vessels of the liver parenchyma during the extended period of time. The present study suggests that the new synthesized gadolinium complexes can be used as a new class of practical liver-specific MRI contrast agent because of its superior performance compared with Gd-DTPA.     

The detection limit of a Gd3+-based T1 agent is substantially reduced when targeted to a protein microdomain

Simple low molecular weight (MW) chelates of Gd(3+) such as those currently used in clinical MRI are considered too insensitive for most molecular imaging applications. Here, we evaluated the detection limit (DL) of a molecularly targeted low MW Gd(3+)-based T(1) agent in a model where the receptor concentration was precisely known. The data demonstrate that receptors clustered together to form a microdomain of high local concentration can be imaged successfully even when the bulk concentration of the receptor is quite low. A GdDO3A-peptide identified by phage display to target the anti-FLAG antibody was synthesized, purified and characterized. T(1-)weighted MR images were compared with the agent bound to antibody in bulk solution and with the agent bound to the antibody localized on agarose beads. Fluorescence competition binding assays show that the agent has a high binding affinity (K(D)=150 nM) for the antibody, while the fully bound relaxivity of the GdDO3A-peptide/anti-FLAG antibody in solution was a relatively modest 17 mM(-1) s(-1). The agent/antibody complex was MR silent at concentrations below approximately 9 microM but was detectable down to 4 microM bulk concentrations when presented to antibody clustered together on the surface of agarose beads. These results provided an estimate of the DLs for other T(1)-based agents with higher fully bound relaxivities or multimeric structures bound to clustered receptor molecules. The results demonstrate that the sensitivity of molecularly targeted contrast agents depends on the local microdomain concentration of the target protein and the molecular relaxivity of the bound complex. A model is presented, which predicts that for a molecularly targeted agent consisting of a single Gd(3+) complex with bound relaxivity of 100 mM(-1) s(-1) or, more reasonably, four tethered Gd(3+) complexes each having a bound relaxivity of 25 mM(-1) s(-1), the DL of a protein microdomain is approximately 690 nM at 9.4 T. These experimental and extrapolated DLs are both well below current literature estimates and suggests that detection of low MW molecularly targeted T(1) agents is not an unrealistic goal.     

Co-Assembly of Gd(III)-Based Metallosurfactant and Conjugated Polymer Nanoparticles in Organosilica Cross-Linked Block Copolymer Micelles for Highly Efficient MRI and Fluorescent Bimodal Imaging

Conformity of two biological imaging entities, magnetic resonance imaging (MRI) and fluorescence imaging, is achieved through co-assembly of a Gd(III)-based metallosurfactant, conjugated polymeric nanoparticles, and amphiphilic block copolymer F127 (PEO₁₀₆PPO₇₀PEO₁₀₆) followed by crosslinking with organosilica. The cross-linked micelles with a size around 100 nm exhibit outstanding dispersion stability in aqueous and phosphate buffered saline solutions, bright fluorescence emission, and high relaxivities, providing a new approach to synthesize highly efficient bimodal contrast agents. The relaxivities of the co-assembled micelles are synergistically enhanced by incorporation of Gd(III) complexes with high hydration number (q = 3) and elongation of rotation correlation time to achieve r₁ values up to 105.37 mm ⁻¹ s⁻¹ (at 1.5 T), which is over 20 times that of clinically used MRI contrast agents and among the highest values of all the nanoparticular MRI contrast agents. The external PEO layer endows these micelles with very low cytotoxicity for both in vitro and in vivo imaging. Meanwhile, thanks to the enhanced permeability and retention effect originating from their nanoscale sizes, the bimodal contrast agents show a prolonged blood circulation time in vivo and targeted accumulation at tumor regions to display outstanding MRI imaging performance.     

基于动态有机钆纳米颗粒的T1-T2双模态MRI造影剂

本文设计、合成并测试了一种新型的基于有机钆纳米颗粒的磁共振成像（MRI）造影剂.以1, 2-氨基硫醇与氰基的缩合反应为基础,成功合成了粒径在8~23 nm范围内的有机钆纳米颗粒.该有机钆纳米颗粒作为磁共振造影剂时,随着时间的推移,其纵向弛豫率逐渐减弱,横向弛豫率先增强后逐渐减弱,这与钆纳米颗粒粒径增大有关.有机钆纳米颗粒同时存在随时间变化的纵向弛豫和横向弛豫,表明它有望成为一种先进的T₁-T₂双模态MRI造影剂.     

L-赖氨酸长链烷基酯双DTPA酰胺钆(Ⅲ)配合物的合成、表征与弛豫效能

通过二乙三胺五乙酸单环酸酐(DTPA-MA)分别与L-赖氨酸的十八酯、十六酯、十四酯和十二酯的双酰化反应, 制得四种含有双DTPA螯合单元的新型配体. 它们与GdCl3·6H2O配合得到相应的双核钆(Ⅲ)配合物. 表征了配体和配合物的结构, 测试了配合物的纵向弛豫效能(R1). 结果表明: 这四种新钆配合物的R1都高于Gd-DTPA.     

Epitaxial growth and band alignment of (Gd(x)La(1-x))(2)O(3) films on n-GaAs (001)

Herein we demonstrate the epitaxial stabilization of single-crystalline (Gd(x)La(1-x))(2)O(3) films on n-GaAs (001) with a controlled lattice match. (Gd(x)La(1-x))(2)O(3) films have an in-plane epitaxial relationship with a twofold rotation on GaAs (001). Spectroscopic characterization by photoemission and absorption confirms that the band gap of (Gd(x)La(1-x))(2)O(3) film is approximately approximately 5.8eV. However, the conduction band offset is increased by the unpinned Fermi level of the n-GaAs in the (Gd(x)La(1-x))(2)O(3) film (x=0.97). The correlation of the crystalline property and the interfacial band offset by the electrical properties, as probed by capacitance and leakage current measurements, is also discussed.     

Dynamic contrast-enhanced MRI of Implanted VX2 tumors in rabbit muscle: comparison of Gd-DTPA and NMS60

We studied the dynamics of injected contrast enhancement in implanted VX2 tumors in rabbit thigh muscle. We compared two contrast agents Gd-DTPA and NMS60, a novel gadolinium containing trimer of molecular weight 2.1 kd. T1-weighted spin echo images were acquired preinjection and at 5-60 min after i.v. injection of 0.1 mmol/kg of agent. Dynamic T1-weighted SPGR images (1.9 s/image) were acquired during the bolus injection. Male NZW rabbits (n = 13) were implanted with approximately 2 x 10(6) VX2 tumor cells and grew tumors of 28+/-27 mL over 12 to 21 days. NMS60 showed significantly greater peak enhancement in muscle, tumor rim, and core compared to DTPA in both T1-weighted and SPGR images. NMS60 also showed delayed peak enhancement in the dynamic scans (compared to Gd-DTPA) and significantly reduced leakage rate constant into the extravascular space for tumor rim (K21 = 5.1 min(-1) vs. 11.5 min(-1) based on a 2 compartment kinetic model). The intermediate weight contrast agent NMS60 offers greater tumor enhancement than Gd-DTPA and may offer improved regional differentiation on the basis of vascular permeability in tumors.