Gadofluorine m uptake in stem cells as a new magnetic resonance imaging tracking method: an in vitro and in vivo study

OBJECTIVES: Cell tracking using ultrasmall iron particles is well established in magnetic resonance imaging (MRI). However, in experimental models, intrinsic iron signals derived from erythrocytes mask the labeled cells. Therefore, we evaluated Gadofluorine M with other gadolinium chelates for a T1-weighted positive enhancement for cell tracking in vitro. In addition, Gadofluorine M was tested in vivo. MATERIAL AND METHODS: Gadofluorine M and other gadolinium chelates were used to label stem cells with and without uptake-mediating agents in vitro and in vivo using a 1.5 T MRI. In addition, histology and molecular modeling was investigated. RESULTS: Gadofluorine M revealed comparable properties to an uptake mediating agent in molecular modeling. Without an uptake-mediating agent Gadofluorine M-labeled cells were detected as a T1-weighted positive contrast in vitro and in vivo. Histology confirmed a 100% success rate for intracellular labeling. CONCLUSION: This study describes a novel contrast agent with the capability of intracellular accumulation without an uptake mediator providing a T1-positive MRI signal at 1.5 T and may be suitable for cell tracking in animal models with intraparenchymal hemorrhages such as stroke or malignant tumors.     

Cell labeling with the positive MR contrast agent Gadofluorine M

The purpose of this study was to label human monocytes with Gadofluorine M by simple incubation for subsequent cell depiction at 1.5 and 3 T. Gadofluorine M displays a high r(1) relaxivity and is spontaneously phagocytosed by macrophages. Human monocytes were incubated with Gadofluorine M-Cy at varying concentrations and incubation times and underwent MR imaging at 1.5 and 3 T at increasing time intervals after the labeling procedure. R1-relaxation rates and r1 relaxivities of the labeled cells and non-labeled controls were determined. Cellular contrast agent uptake was examined by fluorescence microscopy and quantified by ICP-AES. Efficient cell labeling was achieved after incubation of the cells with 25 mM Gd Gadofluorine M for 12 h, resulting in a maximal uptake of 0.3 fmol Gd/cell without impairment of cell viability. Fluorescence microscopy confirmed internalization of the fluorescent contrast agent by monocytes. The r1 relaxivity of the labeled cells was 137 mM(-1)s(-1) at 1.5 T and 80.46 mM(-1)s(-1) at 3 T. Imaging studies showed stable labeling for at least 7 days. Human monocytes can be effectively labeled for MR imaging with Gadofluorine M. Potential in vivo cell-tracking applications include targeting of inflammatory processes with Gadofluorine-labeled leukocytes or monitoring of stem cell therapies for the treatment of arthritis.     

Efficient in vitro labeling rabbit neural stem cell with paramagnetic Gd-DTPA and fluorescent substance

Objectives

The aim of this study is to label rabbit neural stem cells (NSCs) by using standard contrast agents (Gd-DTPA) in combination with PKH26 and in vitro track them with MR imaging.

Materials and methods

NSCs from prenatal brains of rabbits were cultured and propagated. Intracellular uptake of Gd-DTPA was achieved by using a non-liposomal lipid transfection reagent (Effectene) as the transfection agent. After labeling with Gd-DTPA, cells were incubated with cellular membrane fluorescent dye PKH26. The labeling effectiveness and the longevity of Gd-DTPA maintenance were measured on a 1.5 T MR scanner. The influence of labeling on the cellular biological behaviors was assessed by cellular viability, proliferation and differentiation assessment.

Results

The labeling efficiency of Gd-DTPA was up to 90%. The signal intensity on T1-weighted imaging and T1 values of labeled cells were significantly higher than those of unlabeled cells (P < 0.05). The minimal number of detectable cells for T1-weighted imaging was 5 × 10³. Cellular uptake of Gd-DTPA was maintained until 15 days after initially labeling. There was no significant difference in the cellular viability and proliferation between the labeled and unlabeled NSCs (P > 0.05). Normal glial and neuronal differentiation remained in labeled NSCs like unlabeled NSCs.

Conclusion

Highly efficient labeling NSCs with Gd-DTPA could be achieved by using Effectene. This method of labeling NSCs allows for tracking cells with MR imaging, and without alterations of cellular biological behaviors.     

Targeting of hematopoietic progenitor cells with MR contrast agents

PURPOSE: To label human hematopoietic progenitor cells with various magnetic resonance (MR) imaging contrast agents and to obtain 1.5-T MR images of them. MATERIALS AND METHODS: Hematopoietic progenitor cells, labeled with ferumoxides, ferumoxtran, magnetic polysaccharide nanoparticles-transferrin, P7228 liposomes, and gadopentetate dimeglumine liposomes underwent MR imaging with T1- and T2-weighted spin-echo and fast field-echo sequences. Data were analyzed by measuring MR signal intensities and R1 and R2* relaxation rates of labeled cells and nonlabeled control cells. Mean quantitative data for the various contrast agent groups were assessed for significant differences compared with control cells by means of the Scheffe test. As a standard of reference, MR imaging data were compared with electron microscopic and spectrometric data. RESULTS: For all contrast agents, intracellular cytoplasm uptake was demonstrated with electron microscopy and was quantified with spectrometry. When compared with nonlabeled control cells, progenitor cells labeled with iron oxides showed significantly (P <.05) increased R2*. Cells labeled with gadopentetate dimeglumine liposomes showed significantly increased R1. Detection thresholds were 5 x 10(5) cells for gadopentetate dimeglumine liposomes and ferumoxtran, 2.5 x 10(5) cells for ferumoxides and P7228 liposomes, and 1 x 10(5) cells for magnetic polysaccharide nanoparticles-transferrin. CONCLUSION: Hematopoietic progenitor cells can be labeled with MR contrast agents and can be depicted with a standard 1.5-T MR imager.     

Magnetically-labeled sensitized splenocytes to identify glioma by MRI: a preliminary study.

This study investigated the feasibility of imaging the migration and incorporation of magnetically-labeled sensitized splenocytes in an experimental 9L glioma brain tumor model. Splenocytes collected from tumor-bearing (sensitized splenocytes) or control (nonsensitized splenocytes) host rats were analyzed to determine the population of different cells, labeled with ferumoxides-protamine sulfate (FePro) and injected intravenously to recipient rats (N=4, for each group) bearing intracranial 9L tumors. Day 3 postinjection of splenocytes multiecho T2*-weighted and three-dimensional (3D) gradient echo MRI were obtained using a 7 Tesla MR system. R2* (1/T2*) maps were created from the T2*-weighted images. Signal intensities (SIs) and R2* values in the tumors and contralateral brain were determined by hand drawn regions of interest (ROIs). Brain sections were stained for the evidence of administered cells. Both 3D and T2*-weighted MRI showed low signal intensity areas in and around the tumors in rats that received labeled sensitized splenocytes. Prussian blue (PB), CD45- and CD8-positive cells were present in areas at the corresponding sites of low signal intensities seen on MRI. Rats that received labeled nonsensitized splenocytes did not show low signal intensity areas or PB positive cells in or around the implanted tumors. In conclusion, the immunogenic reaction can be exploited to delineate recurrent glioma using MRI following systemically delivered magnetically labeled sensitized splenocytes or T-cells.     

Magnetically labeled cells can be detected by MR imaging

To determine the feasibility of MR imaging of magnetically labeled cells, different cell lines were labeled with monocrystalline iron oxide (MION) particles. Phantoms containing MION labeled cells were then assembled and imaged by MR at 1.5 T using T1-weighted and T2-weighted pulse sequences. MION uptake ranged from 8.5 × 10⁴ to 2.9 × 10⁵ particles/cell for tumor cells (9L and LX1, respectively) to 1.5 × 10⁶ to 4.8 × 10⁸ particles/cell for “professional phagocytes” (J774 and peritoneal macrophages, respectively). On the T1-weighted images, cell-internalized MION appeared hyperintense relative to agar and similar to MION in aqueous solution. On T2-weighted images, signal intensity varied according to concentration of MION within cells. Cell-internalized MION caused similar MR signal changes of cells as did free MION; however, at a dose that was an order of magnitude lower, depending on the pulse sequence used. The detectability of MION within cells was approximately 2 ng Fe, which corresponded to 10⁵ tumor cells/well or 5 × 10³ macrophages/well. We conclude that a variety of cells can be efficiently labeled with MION by simple incubation. Intracellular labeling may be used for MR imaging of in vivo cell tracking.     

MRI T-staging of laryngeal tumours: role of contrast medium

Our aim was to evaluate the relative diagnostic accuracy of MRI without contrast medium and MRI before and after contrast medium in the assessment of T-staging of laryngeal tumours. We studied 25 men (mean age 51.8, range 41–61) with laryngeal squamous cell carcinomas, using Spin-echo (SE) T1-weighted and fast SE T2-weighted sequences. The T1-weighted sequences were then repeated after gadolinium-diethylene-triaminepenta-acetic acid (Gd DTPA) 0.1 ml/kg. All patients then underwent biopsy and surgery. Two radiologists independently assessed the anonymised images by filling-out two multiple-choice forms, one for each technique, at a 2 week interval. The forms included a judgement concerning tumour identification and infiltration of the anterior commissure, supraglottic region, arytenoid cartilage, Morgagni's ventricle, paraglottic space, thyroid and cricoid cartilages, thyro-hyo-epiglottic space, vocal cords, subglottic region, and epiglottis. Similar forms were filled out by the surgeon and the pathologist after surgery. The sensitivity, specificity and diagnostic accuracy of MRI were unaffected by the use of contrast medium. Since it did not provide additional staging information, its continued routine use in these cases is not justified. Received: 13 November 1998/Accepted: 6 April 1999     

A cell-culture reactor for the on-line evaluation of radiopharmaceuticals: evaluation of the lumped constant of FDG in human glioma cells.

A fluidized-bed cell-culture reactor with on-line radioactivity detection was developed for the in vitro evaluation of radiopharmaceuticals. The technique was applied to measure the dependency of the lumped constant (LC) of FDG on the glucose concentration in the culture medium in a human glioma cell line. METHODS: Human glioblastoma cells (86HG39) immobilized in open porous microcarriers were cultivated in a continuously operating fluidized-bed bioreactor. At different glucose concentrations in the culture medium, step inputs (0.1 MBq/mL) of FDG were performed and the cellular uptake of FDG was measured on-line and compared with analyzed samples. From these results, the LC of FDG and its dependency on the glucose concentration were calculated. RESULTS: This fluidized-bed technique enabled precise and reproducible adjustment of all relevant experimental parameters, including radiotracer time-concentration course, medium composition, pH, dissolved oxygen and temperature under steady-state conditions, and an on-line determination of the intracellular radiotracer uptake. The immobilized glioma cells formed stable, 3-dimensional, tumor-like spheroids and were continuously proliferating, as proven by an S-phase portion of 25%-40%. For further examination of the cells, an enzymatic method for detachment from the carriers without cellular destruction was introduced. In the FDG experiments, a significant dependency of the LC on the glucose level was found. For normoglycemic glucose concentrations, the LC was determined to be in the range of 0.7+/-0.1, whereas in hypoglycemia LC increased progressively up to a value of 1.22+/-0.01 at a glucose concentration of 3 mmol/L. CONCLUSION: The bioreactor represents an improved in vitro model for the on-line evaluation of radiotracers and combines a wide range of experimental setups and 3-dimensional, tissue-like cell cultivation with a technique for on-line radioactivity detection.     

Investigation of iodine-123-labelled amino acid derivatives for imaging cerebral gliomas: uptake in human glioma cells and evaluation in stereotactically implanted C6 glioma rats

In developing iodine-123-labelled amino acid derivatives for imaging cerebral gliomas by single-photon emission tomography (SPET), we compared p-[123I]iodo-L-phenylalanine (IPA), L-[123I]iodo-1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid (ITIC) and L-3-[123I]iodo-alpha-methyltyrosine (IMT) with regard to their uptake in human glioblastoma T99 and T3868 cells, and thereafter studied the mechanisms promoting the cellular uptake. The potential of the 123I-iodinated agents for use as SPET radiopharmaceuticals was evaluated in healthy experimental rats as well as in rats with stereotactically implanted C6 gliomas. The radiopharmaceutical uptake into glioblastoma cells was rapid, temperature and pH dependent, and linear during the first 5 min. Equilibrium was reached after 15-20 min, except in the case of ITIC, the initial uptake of which gradually decreased from 15 min onwards. The radioactivity concentration in glioma cells following 30-min incubation at 37 degrees C (pH 7.4) varied from 11% to 35% of the total activity per million cells (ITIC < IMT < or = IPA). Competitive inhibition experiments using alpha-(methylamino)-isobutyric acid and 2-amino-2-norbornane-carboxylic acid, known as specific substrates for systems A and L, respectively, as well as representative amino acids preferentially transported by system ASC, indicated that IPA, like IMT, is predominantly mediated by the L and ASC transport systems, while no significant involvement of the A transport system could be demonstrated. By contrast, none of the three principal neutral amino acid transport systems (A, L and ASC) appear to be substantially involved in the uptake of ITIC into glioblastoma cells. Analysis of uptake under conditions that change the cell membrane potential, i.e. in high K+ medium, showed that the membrane potential plays an important role in ITIC uptake. Alteration of the mitochondrial activity by means of valinomycin or nigericin induces a slight increase or decrease in the radiopharmaceutical uptake, suggesting a minor contribution of the mitochondria in the uptake. IPA, IMT and ITIC passed the blood-brain barrier, and thereafter showed efflux from the brain. The radioactivity concentration in healthy rat brain 15 min following intravenous injection varied from 0.07% (ITIC) to 0.27% ID/g (IPA). In comparison, the brain uptake in the stereotactically implanted C6 glioma rats was substantially higher (up to 1.10% ID/g 15 min p.i.), with tumour-to-background ratios greater than 4. These data indicate that IPA and ITIC, like IMT, exhibit interesting biological characteristics which hold promise for in vivo brain tumour investigations by SPET.     

Selective enhancement of experimental rat brain tumors with Gd-TPPS

The synthetic metalloporphyrin gadolinium (III)-tetraphenylporphine sulfonate (TPPS) was successfully used as a contrast agent for in vivo magnetic resonance (MR) imaging of rat brain glioma. After injection of Gd-TPPS, the signal intensity of experimental rat brain glioma distinctly increased on T1-weighted MR images, an effect similar to that produced by the clinically applied MR imaging contrast agent gadolinium diethylenetriaminepentaacetic acid (DTPA). In contrast to other contrast agents studied (Gd-DTPA, manganese [III]-TPPS), Gd-TPPS produced hypointensity in glioma on T2-weighted images. The tumor-selective accumulation of paramagnetic Gd-TPPS in glioma shortened T1 by 53%, from 1,315 msec ± 199 to 628 msec ± 106, and T2 by 34%, from 86 msec ± 4 to 57 msec ± 5 (2 days after injection of 0.25 mmol/kg Gd-TPPS). The relaxation times of normal cortex, striaturn, corpus callosum, and temporal muscle were not significantly affected. As a result, gliomas appeared hyperintense on T1-weighted images and hypointense on T2-weighted images. Owing to the strong effect of Gd-TPPS on the T2 of glioma, normal brain tissue, tumor, and peritumorous edema could be distinguished on T2-weighted images alone.     

Comparison of two superparamagnetic viral-sized iron oxide particles ferumoxides and ferumoxtran-10 with a gadolinium chelate in imaging intracranial tumors

BACKGROUND AND PURPOSE: Ultrasmall superparamagnetic iron oxide particles result in shortening of T1 and T2 relaxation time constants and can be used as MR contrast agents. We tested four hypotheses by evaluating MR images of intracranial tumors after infusion of two iron oxide agents in comparison with a gadolinium chelate: 1) Ferumoxtran in contrast to ferumoxides can be used as an intravenous MR contrast agent in intracranial tumors; 2) ferumoxtran enhancement, albeit delayed, is similar to gadolinium enhancement; 3) ferumoxtran-enhanced MR images in contrast to gadolinium-enhanced MR images may be compared with histologic specimens showing the cellular location of iron oxide particles; 4) ferumoxtran can serve as a model for viral vector delivery. METHODS: In 20 patients, ferumoxides and ferumoxtran were intravenously administered at recommended clinical doses. MR imaging was performed 30 minutes and 4 hours after ferumoxides infusion (n = 3), whereas ferumoxtran-enhanced MR imaging (n = 17) was performed 6 and 24 hours after infusion in the first five patients and 24 hours after infusion in the remaining 12. MR sequences were spin-echo (SE) T1-weighted, fast SE T2- and proton density-weighted, gradient-recalled-echo T2*-weighted, and, in four cases, echo-planar T2-weighted sequences. Representative regions of interest were chosen on pre- and postcontrast images to compare each sequence and signal intensity. RESULTS: Despite some degree of gadolinium enhancement in all tumors, no significant T1 or T2 signal intensity changes were seen after ferumoxides administration at either examination time. Fifteen of 17 patients given ferumoxtrans had T1 and/or T2 shortening consistent with iron penetration into tumor. Histologic examination revealed minimal iron staining of the tumor with strong staining at the periphery of the tumors. CONCLUSION: 1) Ferumoxtran can be used as an intravenous MR contrast agent in intracranial tumors, mostly malignant tumors. 2) Enhancement with ferumoxtran is comparable to but more variable than that with the gadolinium chelate. 3) Histologic examination showed a distribution of ferumoxtran particles similar to that on MR images, but at histology the cellular uptake was primarily by parenchymal cells at the tumor margin. 4) Ferumoxtran may be used as a model for viral vector delivery in malignant brain tumors.     

Bilateral thalamic glioma: case report

We report a 63-year-old man who had a rare bilateral thalamic glioma. He complained of difficulty with calculations and had mental deterioration. T1-weighted images revealed bilateral thalamic swelling with homogeneous low signal and no contrast enhancement. The tumour, showing decrease of N-acetylaspartate and the presence of lactate on magnetic resonance spectroscopy, was diagnosed as an astrocytoma by stereotactic biopsy. Received: 27 August 1999/Accepted: 7 January 2000     

Investigation of iodine-123-labelled amino acid derivatives for imaging cerebral gliomas: uptake in human glioma cells and evaluation in stereotactically implanted C6 glioma rats

In developing iodine-123-labelled amino acid derivatives for imaging cerebral gliomas by single-photon emission tomography (SPET), we compared p-[¹²³I]iodo-l-phenylalanine (IPA), l-[¹²³I]iodo-1,2,3,4-tetrahydro-7-hydroxyisoquinoline-3-carboxylic acid (ITIC) and l-3-[¹²³I]iodo-!-methyltyrosine (IMT) with regard to their uptake in human glioblastoma T99 and T3868 cells, and thereafter studied the mechanisms promoting the cellular uptake. The potential of the ¹²³I-iodinated agents for use as SPET radiopharmaceuticals was evaluated in healthy experimental rats as well as in rats with stereotactically implanted C6 gliomas. The radiopharmaceutical uptake into glioblastoma cells was rapid, temperature and pH dependent, and linear during the first 5 min. Equilibrium was reached after 15-20 min, except in the case of ITIC, the initial uptake of which gradually decreased from 15 min onwards. The radioactivity concentration in glioma cells following 30-min incubation at 37°C (pH 7.4) varied from 11% to 35% of the total activity per million cells (ITIC < IMT h IPA). Competitive inhibition experiments using !-(methylamino)-isobutyric acid and 2-amino-2-norbornane-carboxylic acid, known as specific substrates for systems A and L, respectively, as well as representative amino acids preferentially transported by system ASC, indicated that IPA, like IMT, is predominantly mediated by the L and ASC transport systems, while no significant involvement of the A transport system could be demonstrated. By contrast, none of the three principal neutral amino acid transport systems (A, L and ASC) appear to be substantially involved in the uptake of ITIC into glioblastoma cells. Analysis of uptake under conditions that change the cell membrane potential, i.e. in high K⁺ medium, showed that the membrane potential plays an important role in ITIC uptake. Alteration of the mitochondrial activity by means of valinomycin or nigericin induces a slight increase or decrease in the radiopharmaceutical uptake, suggesting a minor contribution of the mitochondria in the uptake. IPA, IMT and ITIC passed the blood-brain barrier, and thereafter showed efflux from the brain. The radioactivity concentration in healthy rat brain 15 min following intravenous injection varied from 0.07% (ITIC) to 0.27% ID/g (IPA). In comparison, the brain uptake in the stereotactically implanted C6 glioma rats was substantially higher (up to 1.10% ID/g 15 min p.i.), with tumour-to-background ratios greater than 4. These data indicate that IPA and ITIC, like IMT, exhibit interesting biological characteristics which hold promise for in vivo brain tumour investigations by SPET.     

叶酸受体介导的肿瘤靶向超顺磁性纳米胶束的制备及体外实验

目的探讨叶酸受体介导的两亲聚合物纳米胶束对人肝癌Bel 7402细胞的靶向性，及利用MR仪对其进行监测的可行性。方法制备由叶酸修饰的、载有超顺磁性氧化铁（SPIO）及抗癌药物表阿霉素（DOX）的纳米胶束，将叶酸靶向及非叶酸靶向纳米胶束分别与人肝癌Bel 7402细胞共孵育1h，进行普鲁士蓝染色和流式细胞术观察Bel 7402细胞对叶酸靶向及非叶酸靶向纳米胶束的吸收情况，并体外MRI观察T2WI信号强度变化。结果叶酸靶向纳米胶束与Bel 7402细胞共孵育后普鲁士蓝染色显示细胞内大量铁存在；非叶酸靶向纳米胶束普鲁士蓝染色显示细胞内铁浓度极低。流式细胞术显示叶酸靶向组及非叶酸靶向组的平均荧光强度分别为117．88和46．33，叶酸靶向组约为非叶酸靶向组的2．5倍。体外MRI显示叶酸靶向纳米胶束与Bel 7402细胞共孵育后在T2WI上信号明显降低（SPIO浓度为5、10、20、40和80μg／ml时，信号变化率中位数分别为-5．02％、-23．58％、-45．89％、-70．34％和-92．41％），而非叶酸靶向组在T2WI上信号无明显降低（SPIO浓度为5、10、20、40和80μg／ml时信号变化率中位数分别为-3．77％、-2．16％、-2．18％、-2．74％和-19．77％）。体外竞争抑制实验普鲁士蓝染色显示细胞内铁浓度极低。结论以叶酸修饰的生物可降解聚合物纳米胶束对人肝癌细胞Bel 7402有较好的靶向性，使用临床型MR仪可对其进行监测。     

Comparison of Gd-DTPA-induced signal enhancements in rat brain C6 glioma among different pulse sequences in 3-Tesla magnetic resonance imaging

Background: T1-shortening contrast media are routinely used in magnetic resonance (MR) examinations for the diagnosis of brain tumors. Although some studies show a benefit of 3 Tesla (T) compared to 1.5T in delineation of brain tumors using contrast media, it is unclear which pulse sequences are optimal.

Purpose: To compare gadopentetate dimeglumine (Gd-DTPA)-induced signal enhancements in rat brain C6 glioma in the thalamus region among different pulse sequences in 3T MR imaging.

Material and Methods: Five rats with a surgically implanted C6 glioma in their thalamus were examined. T1-weighted brain images of the five rats were acquired before and after Gd-DTPA administration (0.1 mmol/kg) using three clinically available pulse sequences (spin echo [SE], fast SE [FSE], fast spoiled gradient echo [FSPGR]) at 3T. Signal enhancement in the glioma (E_T) was calculated as the signal intensity after Gd-DTPA administration scaled by that before administration. Pulse sequences were compared using the Tukey-Kramer test.

Results: E_T was 1.12±0.05 for FSE, 1.26±0.11 for FSPGR, and 1.20±0.11 for SE. FSPGR showed significantly higher signal enhancement than FSE and comparable enhancement to SE.

Conclusion: FSPGR is superior to FSE and comparable to SE in its ability to delineate rat brain C6 glioma in the thalamus region.     

New similarity search based glioma grading

Introduction

MR-based differentiation between low- and high-grade gliomas is predominately based on contrast-enhanced T1-weighted images (CE-T1w). However, functional MR sequences as perfusion- and diffusion-weighted sequences can provide additional information on tumor grade. Here, we tested the potential of a recently developed similarity search based method that integrates information of CE-T1w and perfusion maps for non-invasive MR-based glioma grading.

Methods

We prospectively included 37 untreated glioma patients (23 grade I/II, 14 grade III gliomas), in whom 3T MRI with FLAIR, pre- and post-contrast T1-weighted, and perfusion sequences was performed. Cerebral blood volume, cerebral blood flow, and mean transit time maps as well as CE-T1w images were used as input for the similarity search. Data sets were preprocessed and converted to four-dimensional Gaussian Mixture Models that considered correlations between the different MR sequences. For each patient, a so-called tumor feature vector (= probability-based classifier) was defined and used for grading. Biopsy was used as gold standard, and similarity based grading was compared to grading solely based on CE-T1w.

Results

Accuracy, sensitivity, and specificity of pure CE-T1w based glioma grading were 64.9%, 78.6%, and 56.5%, respectively. Similarity search based tumor grading allowed differentiation between low-grade (I or II) and high-grade (III) gliomas with an accuracy, sensitivity, and specificity of 83.8%, 78.6%, and 87.0%.

Conclusion

Our findings indicate that integration of perfusion parameters and CE-T1w information in a semi-automatic similarity search based analysis improves the potential of MR-based glioma grading compared to CE-T1w data alone.     

Gadofluorine-enhanced magnetic resonance imaging of carotid atherosclerosis in Yucatan miniswine

OBJECTIVE: The aim of this study was to determine whether gadofluorine, a paramagnetic magnetic resonance imaging (MRI) contrast agent, selectively enhances carotid atherosclerotic plaques in Yucatan miniswine. METHODS: Atherosclerotic plaques were induced in the left carotid arteries (LCA) of Yucatan miniswine (n=3) by balloon denudation and high cholesterol diet. T1-weighted MRI was performed before and 24 hours after gadofluorine injection (at a dose of 100 micromol/kg) to assess the enhancement of the balloon-injured LCA wall relative to healthy, uninjured right carotid artery (RCA) wall. Histopathology was performed to verify the presence and composition of the atherosclerotic plaques imaged with MRI. RESULTS: Gadofluorine was found to enhance LCA atherosclerotic lesions relative to RCA wall by 21% (P<0.025) 24 hours after contrast injection. Enhancement of healthy LCA wall relative to healthy RCA wall was not observed. CONCLUSION: Gadofluorine selectively enhances carotid atherosclerotic plaques in Yucatan miniswine. Gadofluorine appears to be a promising MR contrast agent for detection of atherosclerotic plaques in vivo.     

A transferrin-mediated uptake of gallium-67 by EMT-6 sarcoma. I. Studies in tissue culture

We have studied the in vitro uptake of gallium-67 by exponentially growing EMT-6 sarcoma cells in long-term tissue culture. In this system, the addition of transferrin to the medium was required before an appreciable cellular uptake of Ga-67 occurred. The transferrin effect was complex, with an initial stimulation to a peak cell-to-medium ratio of 8--10:1 at low concentrations of transferrin (0.2 mg/ml), followed by a gradual decline in uptake as transferrin in the medium was increased further. EMT-6 tumor-cell uptake of Ga-67 was probably mediated by a specific cellular receptor for transferrin. Scatchard analysis of the EMT-6 cellular binding of human transferrin labeled with iodine-125 indicated a cellular receptor with affinity for transferrin of 5 X 10(6) l/mole and abundance of 500,000 receptors per cell. Over the experimental range of transferrin concentration in the medium, the observed uptake of Ga-67 was closely correlated with the degree of formation of Ga-67-labeled transferrin and the fraction of transferrin bound to the cellular receptor (N = 69, r = 0.86, p less than 0.0001).     

99Tc m标记lncRNA HOTAIR反义寡核苷酸探针的制备及其对人脑胶质瘤U87细胞活性的影响

目的:制备新型的靶向长链非编码RNA （lncRNA）同源异型盒基因转录的反义基因间RNA (HOTAIR）的反义寡核苷酸（ASON）探针 99Tc m-HYNIC-ASON (HYNIC为联肼尼克酰胺）,探讨其对人脑胶质瘤U87细胞增殖和迁移能力的影响。 方法:设计并通过化学修饰合成...     

碘125治疗裸鼠胶质瘤的实验研究

目的:通过建立裸鼠右肩皮下C6胶质瘤动物模型,研究碘125间质内照射对恶性胶质瘤的治疗作用。方法:Balb/c裸鼠30只。体外培养大鼠C6胶质瘤细胞,接种于裸鼠右肩皮下建立肿瘤模型。肿瘤形成后对照组(15只),注入无碘125材料,治疗组(15只)肿瘤中心注入碘125聚胺酯放射材料,4周时对比两组肿瘤体积、瘤重并处死取病理行组织学检查分析。结果:C6细胞接种后1周,裸鼠皮下均可见肿瘤形成。4周时对照组与治疗组肿瘤体积、瘤重差异明显(P<0.05),病理组织学检查见对照组肿瘤细胞呈典型的恶性星形细胞瘤特征,治疗组肿瘤细胞体积缩小及大量坏死。结论:碘125聚胺酯放射材料可通过间质内照射对C6胶质瘤细胞产生杀伤作用,明显抑制肿瘤生长。