| Hepatocyte targeting with Gd-EOB-DTPA: potential application for gene therapy. | |
| | |
MedLine Citation:
|
PMID: 11176256 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
RATIONALE AND OBJECTIVES: To evaluate the suitability of the liver-specific MRI contrast agent Gd-EOB-DTPA as a nonviral vector for gene therapy of hepatocellular carcinoma. METHODS: Specific uptake of Gd-EOB-DTPA was quantified by relaxometry in rat cultured hepatocytes and the hepatoma cells HepG2 and Huh7. Nonviral vectors for gene transfer were synthesized by coupling Gd-EOB-DTPA to polyethyleneimine or polylysine as DNA condensing agents, and their efficiency was studied using beta-galactosidase (lacZ) as the reporter gene. RESULTS: Gd-EOB-DTPA was specifically taken up by rat cultured hepatocytes (4.32 vs. 1.08 mmol/L in nonhepatocyte control cells) but not by the hepatoma cells; this uptake was concentration-dependently inhibited by Bromsulphtalein. Polycation linkages were achieved with yields of 0.9 Gd-EOB-DTPA molecule per polyethyleneimine molecule and 10 Gd-EOB-DTPA molecules per polylysine molecule. Incubating the cells with plasmids containing lacZ reporter gene and polyethyleneimine-Gd-EOB-DTPA resulted in a few blue (transfected) cells, whereas no blue cells were observed on incubation with polylysine-Gd-EOB-DTPA. CONCLUSIONS: Gd-EOB-DTPA is taken up by normal hepatocytes but not by HepG2 and Huh7 cells, probably because of the lack of the organic anion transporter in these hepatoma cells. The Gd-EOB-DTPA polycation conjugates, such as polyethyleneimine-Gd-EOB-DTPA, could serve as transfer vectors of interest for gene targeting imagery at the early stage of hepatocarcinogenesis. However, the transfer efficiency of such conjugates is low and requires improvement. |
| | |
Authors:
|
M Lewin; O Clément; P Belguise-Valladier; L Tran; C A Cuénod; N Siauve; G Frija |
Related Documents
:
|
195426 - Activity of chromatin-bound protease from rat liver and morris hepatomas. 445436 - Increased survival of rats bearing morris hepatoma 7800 after induction of hypothyroidism. 57896 - Beta-glucuronidase activity of yoshida ascites hepatomas of different drug-sensitivity ... 6690036 - Retinyl palmitate, retinyl phosphate, and dolichyl phosphate of postnuclear membrane fr... 7657546 - Effect of prior oxygen exposure on the electroretinographic responses of infant rats. 740126 - A possible mechanism for cholesteryl ester formation during demyelination: lecithin:cho... |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Investigative radiology Volume: 36 ISSN: 0020-9996 ISO Abbreviation: Invest Radiol Publication Date: 2001 Jan |
Date Detail:
|
Created Date: 2001-01-23 Completed Date: 2001-06-07 Revised Date: 2009-11-11 |
Medline Journal Info:
|
Nlm Unique ID: 0045377 Medline TA: Invest Radiol Country: United States |
Other Details:
|
Languages: eng Pagination: 9-14 Citation Subset: IM |
Affiliation:
|
Laboratoire d'Imagerie, Unité Inserm 494, Faculty of Medecine Necker, Paris, France. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Carcinoma, Hepatocellular / drug therapy* Contrast Media / therapeutic use* Gadolinium DTPA / therapeutic use* Gene Therapy / methods* Hepatocytes Liver Neoplasms / drug therapy* Rats Transfection Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
|
0/Contrast Media; 0/gadolinium ethoxybenzyl DTPA; 80529-93-7/Gadolinium DTPA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Neurotolerability of contrast agents in rats with brain ischemia induced by transient middle cerebra...
Next Document: Detection of experimental hepatic tumors using long circulating superparamagnetic particles.