MION-ASF - BIOKINETICS OF AN MR RECEPTOR AGENT

被引:48
作者
SCHAFFER, BK [1 ]
LINKER, C [1 ]
PAPISOV, M [1 ]
TSAI, E [1 ]
NOSSIFF, N [1 ]
SHIBATA, T [1 ]
BOGDANOV, A [1 ]
BRADY, TJ [1 ]
WEISSLEDER, R [1 ]
机构
[1] MASSACHUSETTS GEN HOSP,DEPT RADIOL,BOSTON,MA 02114
关键词
MAGNETICS; MAGNETISM; MRI; CONTRAST AGENT; IRON OXIDE; ASIALOFETUIN; ASIALOGLYCOPROTEIN; RECEPTOR;
D O I
10.1016/0730-725X(93)90074-N
中图分类号
R8 [特种医学]; R445 [影像诊断学];
学科分类号
1002 ; 100207 ; 1009 ;
摘要
Receptor-directed MR contrast agents are currently being designed to improve sensitivity and specificity of MR imaging and to provide for functional MR imaging. In the current study we have synthesized a conjugate of asialofetuin (ASF), a bovine plasma protein with a known, high affinity f or the hepatic asialoglycoprotein receptor, and a well defined, single crystal superparamagnetic label (monocrystalline iron oxide nanoparticle, MION). MION-ASF is cleared f rom the circulation more than 300 times faster than MION, has a 3.7 times higher hepatic accumulation, increases liver R2 relaxivity 2.8-fold compared to MION, and accumulates in hepatocytes unlike MION, which accumulates only in macrophages. Competition assays indicate that receptor-mediated hepatocyte uptake can be competitively blocked and that this effect can be demonstrated by imaging. These studies indicate that sensitive iron oxide based probes can be developed for functional MR imaging.
引用
收藏
页码:411 / 417
页数:7
相关论文
共 16 条
[1]  
Vera, Stadalnik, Krohn, Technetium-99m galactosylneoglycolalbumin: Preparation and preclinical studies, J. Nucl. Med., 26, pp. 1157-1167, (1985)
[2]  
Stadalnik, Vera, Krohn, Receptor-Binding Radiopharmaceuticals: Experimental and Clinical Aspects, pp. 105-139, (1986)
[3]  
Weissleder, Reimer, Lee, Wittenberg, Brady, MR receptor imaging: Ultrasmall iron oxide particles targeted to asialoglycoprotein receptors, AJR, 155, pp. 1161-1167, (1990)
[4]  
Josephson, Groman, Menz, Luis, Bengele, A functionalized superparamagnetic iron oxide colloid as a receptor directed MR contrast agent, Magn. Reson. Imaging, 8, pp. 637-646, (1990)
[5]  
Ashwell, Harford, Carbohydrate-specific receptors of the liver, Ann. Rev. Biochem., 51, pp. 531-554, (1982)
[6]  
Tolleshaug, Berg, Investigation of the uptake of asialo-glycoproteins by isolated rat hepatocytes. Implications for its biological significance, Hoppe Seylers Z Physiol. Chem., 361, pp. 1155-1164, (1980)
[7]  
Weiss, The pathophysiology of metastasis within the lymphatic system, Lymphatic System Metastases, pp. 2-40, (1988)
[8]  
Harford, Ashwell, Assessment of receptor recycling in mammalian hepatocytes: Perspectives based on current techniques, Meth. Enzymol., 109, pp. 232-246, (1985)
[9]  
Dautry-Varsat, Lodish, How receptors bring proteins and particles into cells, Scientific American, 240, pp. 52-58, (1984)
[10]  
Molday, Molday, Separation of cells labeled with immunospecific iron dextran micropheres using high gradient magnetic chromatography, FEBS Lett., 170, pp. 232-238, (1984)