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1.
Strich  G; Hagan  PL; Gerber  KH; Slutsky  RA 《Radiology》1985,154(3):723-726
Gadolinium-DTPA complex (Gd-DTPA) is a potential clinical magnetic resonance (MR) contrast agent that enhances images primarily by decreasing spin-lattice relaxation time (T1) in tissues in which it localizes. This study was designed to determine the immediate tissue distribution of intravenously administered Gd-DTPA in selected organs of interest as a function of administered dose and tissue Gd-DTPA concentration. An intravenous bolus of Gd-DTPA with a tracer quantity of Gd-153 was administered to three groups of rabbits at the following doses: 0.01 mM/kg (n = 6); 0.05 mM/kg (n = 6); 0.10 mM/kg (n = 6). A control group received sham injections. Five minutes after Gd-DTPA was administered, all animals were killed; samples of serum, lung, heart, kidney, liver, and spleen were analyzed in a 0.25 T MR spectrometer to measure T1, and then in a gamma well counter to determine tissue concentration of Gd-DTPA. Tissue distribution (per cent dose/tissue weight in g) at five minutes after injection was proportionally constant over the range of doses given. Tissue concentration varied linearly with injected dose (r greater than 0.98 for all tissues). Relaxation rate (1/T1) varied linearly with injected dose and with tissue Gd-DTPA concentration (r greater than 0.97 for all tissues). The order of tissue relaxation rate response to a given dose was: kidney greater than serum greater than lung greater than heart greater than liver greater than spleen. We conclude that because of its extracellular distribution and linear relaxation rate versus concentration relationship, Gd-DTPA enhancement in MR images may be a good marker of relative organ perfusion.  相似文献   

2.
PURPOSE: To design nanoparticles containing accessible gadolinium atoms (Gd-NPs) as a contrast agent for magnetic resonance imaging of tumors. METHODS: Nanoparticles containing phospholipid-chelates (phosphoethanolamine diethylenetriaminepentaacetate) and DSPE-PEG (MW5000) were prepared from Brij 78 and stearyl alcohol using the nanotemplate engineering approach. After addition of GdCl3, the presence of gadolinium on the surface of nanoparticles was quantified using inductively coupled plasma atomic emission spectroscopy. The in vitro relaxivities of the Gd-NPs in phosphate buffered saline were assessed at 4.7 T. The conditional binding constants of nanoparticle formulations were determined spectrophotometrically by competitive titration. Transmetallation kinetics of Gd from nanoparticles with Cu2+ and Zn2+ as the competing ions was measured in acetate buffer. The biodistribution profiles, pharmacokinetics, and contrast enhancement in tumor region was studied after administration of Gd-NPs to nude mice bearing A549 lung carcinoma xenografts. RESULTS: Gd-NPs with an average diameter of 138 nm possessing surface chelating functions were prepared from GRAS (generally regarded as safe) materials. The longitudinal relaxivity (r1) and transverse relaxivity (r2) of Gd-NPs in 10% fetal bovine serum at 4.7 T were 7.1 (+/-0.2) and 13.0 (+/-0.7) 1/mM/s, respectively. These pegylated Gd-NPs had enhanced relaxivities and exhibited particle size stability, sufficient binding affinity, and kinetic inertness under physiologic conditions. The contrast enhancement in tumors was demonstrated 40, 120, and 360 minutes after intravenous injection of Gd-NPs at a dose of 0.1 mmol Gd/kg. The Gd plasma concentration of Gd-NPs over a period of 24 hours fit a two-compartmental model with Cl sys = 0.89 mL/h and MRT = 5.93 h. The amount of Gd that accumulated in the tumor region was consistent with the estimated value obtained by T1 measurements using MR imaging. CONCLUSION: Pegylated nanoparticles composed of biocompatible, biodegradable materials and possessing accessible Gd ions on their surface induce relaxivities in the bulk water signal and accumulated sufficiently in tumors, demonstrating their utility as potential magnetic resonance imaging tumor contrast enhancement agents.  相似文献   

3.
目的:研究双肾藤乙醇提取物对四氧嘧啶糖尿病小鼠的降血糖作用.方法:采用85%乙醇煎煮双肾藤,获得其提取物.采用四氧嘧啶诱发糖尿病,建立糖尿病小鼠模型.双肾藤提取物灌胃给药,第一周剂量为1 000 mg/kg,第2和第3周剂量为500 mg/kg,二甲双胍为阳性药(250 mg/kg).每天测定小鼠饮水量和耗食量,给药7 d和20 d测定小鼠血糖及血浆中总胆固醇、甘油三酯、高密度脂蛋白胆固醇(HDL-C)和胰岛素水平.实验结束后测定小鼠肝脏、肾脏和脾脏重量指数.结果:双肾藤提取物具有显著降血糖活性(P<0.01),效果与二甲双胍相近,能明显减少糖尿病小鼠饮水量和耗食量,轻度降低糖尿病小鼠血浆甘油三酯含量,但对总胆固醇、HDL-C及胰岛素水平无明显影响.该提取物能引起糖尿病小鼠肝脏萎缩.结论:双肾藤提取物对四氧嘧啶糖尿病小鼠具有明显降血糖作用,但可能作用于胰腺外.  相似文献   

4.
B lymphocyte stimulator (BLyS) protein is a member of the tumor necrosis factor (TNF) superfamily of cytokines that binds to B lineage cells, but not T cells, monocytes, natural killer cells, or granulocytes. BLyS protein binding to B cells is restricted to immunoglobulin-positive cells and is not evident on pro- or pre-B cell populations. This unique binding profile suggests that a radiolabeled form of BLyS protein may be a useful treatment for B cell neoplasias such as B cell lymphoma and multiple myeloma. Here, we report the biodistribution of radiolabeled recombinant human BLyS after intravenous injection into normal mice and mice bearing BCL1 tumor in the spleen or J558 tumor in the subcutaneous space. We also report the use of these data to estimate human dosimetry. METHODS: (125)I-Labeled BLyS protein (50 micro g/kg, 0.185-0.37 MBq per mouse) was injected intravenously into BALB/c mice, and biodistribution was measured by direct counting of radioactivity in dissected tissues and by quantitative whole-body autoradiography (QWBA). RESULTS: The half-life of radiolabeled BLyS protein in blood was approximately 2.7 h in both normal and tumor-bearing mice. The spleen showed the highest uptake of BLyS protein in both normal and tumor-bearing mice, with a maximum concentration (C(max)) of 35-45 percentage injected dose per gram (%ID/g) occurring between 1 and 3 h after injection. In lymph nodes, C(max) was approximately 20 %ID/g in normal and J558 tumor-bearing mice and 8-15 %ID/g in BCL1 tumor-bearing mice. Limited biodistribution data from the J558 tumors showed a C(max) of approximately 15 %ID/g. By contrast, C(max) was only approximately 5 %ID/g for both kidney and liver. QWBA confirmed high radioactivity in spleen, lymph nodes, and stomach contents and low radioactivity in kidney and liver. After 24 h, spleen and lymph nodes were still positive in QWBA images, whereas liver and kidney no longer had observable levels. CONCLUSION: Radiolabeled BLyS showed specific and rapid targeting to lymphoid tissues and B cell tumors in mice. Unlike monoclonal antibodies, which have long plasma half-lives and considerable liver uptake, BLyS has distinct pharmacokinetic and biodistribution properties that may offer advantages compared with antibody-based radioimmunotherapy.  相似文献   

5.
The purpose of the study was to determine if derivatization of cholesterol with a paramagnetic label could result in an organ-specific contrast agent for magnetic resonance imaging of the adrenal glands. Gadolinium-DO3A-labeled cholesterol was synthesized and the relaxivities in water and blood plasma determined at 0.47 T and 40°C. Organ distribution was measured at 2 (n = 2) and 24 (n = 2) hours after intravenous injection of a 50 μmol/kg dose of Gd-DO3A-cholesterol in rats weighing 220–240 g. T1-weighted spin-echo images were acquired at 2 T before and after injection of 50 μmol/kg Gd-DO3A-cholesterol (n = 2) and Gd-DTPA (diethylenetriaminepentaacetic acid)-albumin (n = 2). More than 99% of the Gd-DO3A-cholesterol was found to be protein bound in bovine serum. High T1 and T2 relaxivities were found in water and plasma. High tissue concentrations of Gd-DO3A-cholesterol were found only in adrenal glands and liver. At 24 hours, adrenal gadolinium concentrations were about 10 times higher than in blood. At 2 hours after injection of Gd-DO3A-cholesterol. enhancement was 162% in adrenal glands and 146% in liver. With Gd-DTPA-albumin, enhancement values were 57% and 56%. respectively.  相似文献   

6.
Manganese (III) hematoporphyrin (MnHP), a new and stable complex, was prepared, and its toxicity and magnetic resonance (MR) imaging properties were evaluated. In tests of acute and subacute toxicity, no deaths resulted from bolus intravenous injections of 13 or 19 mumols/kg of MnHP, but there was a 33% mortality when the dose was 38 mumols/kg. Laboratory results were normal in the surviving rats. Ultraviolet- visible spectroscopy of the urine and serum of two rats injected 24 hours previously with 38 mumols/kg MnHP revealed no free HP, suggesting in vivo stability of MnHP. Finally, using a standardized imaging protocol, there was a mean increase of 37% in the liver-to-muscle intensity ratios in four rats injected 24 hours previously with 25 mumols/kg MnHP when compared to paired controls (P less than .005). In addition, obvious visual increase in the signal intensity of the liver on T1-weighted images was seen in animals tested with 13 and 19 mumols/kg of MnHP. The results suggest that further evaluation of MnHP as an MR contrast agent for the liver is warranted.  相似文献   

7.
Multiple intravenous injections of contrast media are used in radiology, but information regarding corresponding changes in the serum iodine concentrations and osmolality is lacking. We measured the changes in serum iodine concentration and serum osmolality in rabbits after a series of intravenous injections of contrast media. Hypaque-76 (1 cc/kg) was injected intravenously in awake rabbits at 10-minute intervals for 1 hour and arterial blood sampled at midpoint times between injections. During the 1-hour period of seven serial injections, mean serum iodine concentration at 5 minutes was 2.3 mg I/cc (+/- 0.1 SEM, n = 14); at 35 minutes, 5.1 mg I/cc (+/- 0.2); and at 65 minutes, 6.7 mg I/cc (+/- 0.4). The mean peak concentration was 6.8 mg I/cc (+/- 0.4). Serum osmolality underwent a mean increase of 16 mosm/kg during the injection period. Hypertonic mannitol injections produced a smaller increase in osmolality (10 mosm/kg). Isotonic saline injections in control animals produced no change in osmolality.  相似文献   

8.
The Gd3+-complex of 10-(2,3-dihydroxy-l-hydroxymethylpropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (gadobutrol) is a new, neutral Gd-chelate for use as an extracellular contrast agent in magnetic resonance imaging (MRI). The blood level in dogs after intravenous (i.v.) injection decreased with a terminal half-life of about 45 min, the clearance was about 3.75 ml/min per kg and the distribution volume of 0.23 l/kg suggested an extracellular distribution. Biodistribution experiments in rats revealed that only a very small amount (0.16%) of the dose was left in the body 7 days after i.v. injection. Measurable amounts of Gd could be detected only in the liver, kidneys and bones. The osmolality (0.57 osmol/kg at 0.5 mol/1 and 1.39 osmol/kg at 1 mol/1) is in the range of other low osmolality contrast media for MRI. Only very little interaction with biologically relevant molecules was suggested by a histamine release test and a lysozyme inhibition test. An i.v.-LD50 of 23 mmol/kg in mice combined with a comparatively high T1-relaxivity (5.6 l/mmol per s at 0.47 T and 6.1 l/mmol per s at 2 T) in plasma promises a high margin of safety. In preliminary imaging experiments, gadobutrol caused high enhancement in different lesions (cerebral infarct, brain tumor) of the rat. Tripling of the typical clinical dose of 0.1 mmol/kg was shown to provide additional diagnostic gain in lesions of this type.  相似文献   

9.
To evaluate the potential of dextran-coated magnetite (DM) particles in enhancing the detection of hepatocellular carcinoma with magnetic resonance (MR) imaging, the authors induced liver tumors in rats by oral administration of diethylnitrosamine and examined the rats before and after intravenous injections of DM with various iron concentrations. Because of the intense and preferential T2 relaxativity of DM, use of DM with an iron concentration of 10 mumol/kg yielded effective MR signal reduction in each normal liver at 1 hour after the injection. Because no significant signal change in the tumors was observed on DM-enhanced MR images, the contrast between hepatocellular carcinoma and adjacent uninvolved liver increased remarkably on even relatively T1-weighted images. The detection rate for the 89 tumors, including small tumors less than 2 mm in diameter, increased from 10% (nine of 89) before DM administration to 65% (58 of 89) with DM-enhanced T1-weighted imaging. Iron staining of rat liver performed about 1 hour after DM administration showed sparse deposits of DM selectively in reticuloendothelial cells but not in liver tumors.  相似文献   

10.
Paramagnetic macrocyclic chelates show promise as magnetic resonance (MR) imaging contrast agents due to stability and relaxivity comparable to those of DTPA-type chelates. For the three copper and manganese macrocyclic complexes studied in aqueous solution, T1 and T2 relaxivities ranged from 0.14 to 5.88 mM-1sec-1 at 6.25 MHz. In rats, the intravenous administration of 16 mumol/kg of Mn(cyclam) caused the liver T1 relaxation rate to double at 15 minutes after injection. T1 measurements by pulsed MR imaging and manganese analyses on excised tissue showed that both relaxation rate (1/T1) and manganese content of liver and kidney increase linearly with the dosage of Mn(cyclam). The linear relationship between 1/T1 and manganese content can be considered an "in tissue" relaxivity plot for the agent. The resulting relaxivity is 54 mM-1sec-1 in liver, compared with 3.1 mM-1sec-1 in aqueous solution. Although this work is preliminary, the implication for medical MR imaging applications is that macrocyclic contrast agents can be effective at approximately one-tenth the current typical dose used for gadolinium DTPA.  相似文献   

11.
Gadolinium diethylenetriaminepentaacetic acid (DTPA) covalently linked to the lipophilic ethoxybenzyl moiety (Gd-EOB-DTPA) was designed for use as a contrast agent in hepatobiliary magnetic resonance imaging. With T1 relaxivity values of 8.7 L/mmol.second in plasma and 16.6 L/mmol.second in rat liver tissue and a median lethal dose of 10 mmol/kg when administered intravenously in mice and rats, Gd-EOB-DTPA has a fairly high margin of safety. In rats and monkeys, biodistribution studies performed 7 days after administration of 0.25 mmol/kg revealed very little retention of gadolinium (less than 1%) in the tissues, indicating complete elimination via renal and biliary excretion. Biliary excretion was inhibited by coadministration of sulfobromophthalein, indicating the involvement of a carrier-mediated transport system based on the enzyme glutathione-S-transferase. In rats, the biliary transport maximum was 5 mumol gadolinium/min.kg. High T1 relaxivity of Gd-EOB-DTPA in rat liver in vivo can be explained by transient interaction with intracellular components and by increased microviscosity inside the hepatocyte.  相似文献   

12.
Gadolinium-phthalein complexone (Gd-PC) was developed as a hepatobiliary magnetic resonance (MR) contrast agent. Phthalein complexone is one of the iminodiacetic acid derivatives and a structural analogue of bromosulfophthalein. Gadolinium-PC substantially enhanced signal intensity of normal functioning livers on T1-weighted MR images. Contrast enhancement of rabbit liver and gradual accumulation of high intensity bile in the gallbladder were observed after intravenous injection of 0.05 and 0.1 mmol/kg Gd-PC. However, 0.1 mmol/kg of Gd-DTPA caused little effect on liver MR.  相似文献   

13.
To develop guidelines for clinical magnetic resonance imaging of the liver, the authors undertook an animal study to investigate the effect of dose and pulse sequence on liver signal intensity in gadopentetate dimeglumine—enhanced echo-planar imaging. Serial imaging of the liver was performed in anesthetized rats after intravenous administration of five different doses (0.01, 0.05, 0.1, 0.2, and 0.5 mmol/kg) of contrast agent, with six different pulse sequences. The results show that gadopentetate dimeglumine—enhanced echo-planar images obtained during the perfusion phase can yield either positive (due to increased T1 relaxation rates) or negative (due to susceptibility-induced increased T2 relaxation rates) liver enhancement depending on choice of pulse sequence and dose. At the current clinically recommended dose of 0.1 mmol/kg, maximal liver signal enhancement was seen with a T1-weighted inversion-recovery sequence, while maximal liver signal diminution was seen with a T2*-weighted gradient-echo sequence. The authors conclude that gadopentetate dimeglumine—enhanced echo-planar imaging can provide T1, T2, and T2* contrast that may be exploited for both lesion detection and lesion characterization.  相似文献   

14.
The performance of a newly developed potential tumor-seeking magnetic resonance (MR) contrast agent alpha-Aqua-13,17-bis(1-carboxypropionyl) carbamoylethyl-3,8-bis(1-phenethyloxyethyl)-beta-hydroxy-2,7,12,18-tetramethyl-porphyrinato manganese (III) (HOP-8P) was tested using a mouse model. Tumor-bearing (SCC-VII) mice were imaged using a 1.5T MR imager before and after intravenous administration of 0.1 mmol/kg of HOP-8P. A biodistribution analysis was performed using an optical emission spectrometer. Significant enhancement of the transplanted tumor was observed in MR images 24 h after intravenous injection of HOP-8P. The biodistribution assessment of manganese also correlated with the results of the imaging study. During the 24-h period following contrast administration, HOP-8P was consistently cleared from the circulation, liver, kidneys, and muscle; however, it was progressively accumulated within the tumor. HOP-8P is a promising tumor-seeking metalloporphyrin MR contrast agent with a wide imaging window.  相似文献   

15.
OBJECTIVE: To compare MRI of the liver with mangafodipir trisodium (MnDPDP) and computed tomography with intravenous contrast media in the follow-up of liver metastases in patient on chemotherapy for colorectal carcinoma. MATERIALS AND METHODS: This was a prospective study with patients on chemotherapy for liver metastases from colorectal cancer. Patients underwent both contrast-enhanced helical CT using 2 cc/kg contrast at 3 cc/sec and mangafodipir trisodium-enhanced MR imaging at 1.5 T using 2-3 cc/min contrast at 5 micro mol/kg within a two week interval. Two experienced radiologists independently reviewed all scans in a blinded fashion and recorded image quality as well as presence and number of liver lesions. Statistical analysis was performed using the wilcoxon signed rank test. RESULTS: All examinations were of good quality. A total of 71 lesions were detected at CT, with 69 lesions consistent with metastases and 2 lesions consistent with cysts. A total of 98 lesions were detected at MRI, with 97 consistent with metastases and 1 lesion consistent with a cyst. T1 weighted images with MnDPDP significantly detected two additional lesions compared to CT (p<0.05). No significant difference was demonstrated between T1 weighted images without MnDPDP and CT or between T2 weighted images and CT. CONCLUSION: Magnetic resonance imaging with MnDPDP is significantly more sensitive than unenhanced MRI and helical CT for the follow-up of liver lesions.  相似文献   

16.
封闭和不封闭BALB/c小鼠库普弗细胞48h后,夹闭肠系膜上动脉1h后松夹,复制肠缺血再灌注模型。运用原位细胞DNA末端标记和流式细胞术检测缺血前、缺血60min、再灌注30、60min肝、脾、胸腺细胞的凋亡情况。  相似文献   

17.
A new tissue-equivalent MRI phantom based on carrageenan gel was developed. Carrageenan gel is an ideal solidifying agent for making large, strong phantoms in a wide variety of shapes. GdCl(3) was added as a T(1) modifier and agarose as a T(2) modifier. The relaxation times of a very large number of samples were estimated using 1.5-T clinical MRI equipment. The developed phantom was found to have a T(1) value of 202-1904 ms and a T(2) value of 38-423 ms when the GdCl(3) concentration was varied from 0-140 mumol/kg and the agarose concentration was varied from 0-1.6% in a carrageenan concentration that was fixed at 3%. The range of measured relaxation times covered those of all types of human tissue. Empirical formulas linking the relaxation time with the concentration of the modifier were established to enable the accurate and easy calculation of the modifier concentration needed to achieve the required relaxation times. This enables the creation of a phantom having an arbitrary combination of T(1) and T(2) values and which is capable of retaining its shape.  相似文献   

18.
目的 观察不同剂量的茶多酚(TP)、维生素C(Vit C)对FeSO4-半胱氨酸诱发离体人血浆脂质过氧化及CCl4诱发肝自由基损伤的抑制作用。方法 (1)在FeSO4-半胱氨酸诱发离体人血浆脂质过氧化损伤体系中,分别检测0.3、0.9、2.7、8.1mg/L(C-F组)的TP及3、9、27、81mg/L(G-J组)的Vit C对该体系过氧化脂质(MDA)生成的影响;(2)雄性昆明种小鼠36只,随机分为4组(n=9),分别为空白对照组(A)、单纯损伤组(B)、茶多酚100mg/kg组(C),以及Vit C 100mg/kg组(D)。除空白对照外,用药组以相应剂量的防护药物灌胃1次/日,共3次。末次灌胃12h后,除空白对照外,其他3组均用230mg/kg的CCl4灌胃,36h后,各组小鼠均断头处死,分别检测肝匀浆中MDA的含量。结果 TP、Vit C均可剂量相关地抑制FeSO4-半胱氨酸诱发的离体人血浆脂质过氧化损伤,其中TP抑制率分别为30.7%、32.0%、46.9%、59.7%;Vit C的抑制率分别为8.3%、41.4%、47.7%、52.7%。在CCl4诱发肝自由基损伤体系中,同等剂最的TP、Vit C对MDA的抑制率分别为45.2%、42.8%。结论 在FeSO4-半胱氨酸诱发的人离体血浆过氧化损伤体系中,TP(0.3-8.1mg/L)及Vit C(9-81mg/L)对脂质过氧化均有明显的抑制作用(P<0.01);同等剂量下,TP对该体系中脂质过氧化的抑制作用优于Vit C。在CCl4诱发肝自由基损伤体系中,TP和Vit C对脂质过氧化均有明显的抑制作用,但者之间无显著差异。  相似文献   

19.
目的探讨芬太尼滴鼻用于人工流产术的安全性和有效性。方法60例美国麻醉医师协会(ASA)分级Ⅰ或Ⅱ级,年龄20~40岁,体重40~65kg,随机均分为两组,芬太尼稀释至2mL:观察组(A组)经鼻滴入芬太尼1μg/kg;对照组(B组)静注芬太尼1μg/kg。患者用药2min后均静注丙泊酚1.5~2mg/kg,患者意识消失即开始手术,酌情追加丙泊酚0.5~1mg/kg。记录用药前(T0)、用药后2min(T1)、静注丙泊酚后1min(T1)、2min(T3)及清醒时(L)的平均动脉压(MAP)、心率(HR)、脉搏氧饱和度(SpO2)、丙泊酚用量、诊疗时间、意识恢复时间、术后恶心、呕吐、嗜睡发生情况。结果MAP两组在T1~T4时均低于L时(P〈0.05),组间比较无统计学意义,SpO2在T2、B时A组低于B组(P〈0.05),B组T1~T3时低于T0时(P〈0.05);丙泊酚用量两组差异无统计学意义。结论1μg/kg芬太尼滴鼻复合丙泊酚静注用于人工流产术是安全有效的。  相似文献   

20.
OBJECTIVES. Manganese (III) mesoporphyrin (Mn-mesoporphyrin), a synthetic and stable complex, was investigated for its hepatic magnetic resonance imaging (MRI) properties and compared with manganese tetrakis-(4 sulfonatophenyl) porphyrin (Mn-TPPS4). METHODS. Liver abscesses (n = 10) and tumors (n = 14) were induced in rats. These rats then underwent MRI at 2.0 T. Animals received one of the two contrast agents, and measurement of lesion enhancement was performed. RESULTS. At an intravenous dose of 0.035 mmol/kg, Mn-mesoporphyrin caused significant enhancement of normal liver parenchyma and increased the lesion-to-liver contrast in both the models of heptic liver abscess and metastatic liver disease. Mn-TTPS4 at an intravenous dose of 0.04 mmol/kg typically enhanced both lesion and normal liver parenchyma and therefore did not improve the lesion-to-liver contrast. CONCLUSIONS. The hepatotrophic properties of Mn-mesoporphyrin indicate its potential as an intravenous contrast agent for liver imaging.  相似文献   

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