Polylysine-Gd-DTPAn and polylysine-Gd-DOTAn coupled to anti-CEA F(ab')2 fragments as potential immunocontrast agents. Relaxometry, biodistribution, and magnetic resonance imaging in nude mice grafted with human colorectal carcinoma
| Autor: | Anil Mishra, Jean-François Chatal, C. Curtet, Robert N. Muller, Micha Slinkin, Frédéric Maton, Thierry Havet |
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| Rok vydání: | 1998 |
| Předmět: |
Gadolinium DTPA
Relaxometry Biodistribution Immunoconjugates Colorectal cancer Contrast Media Mice Nude Adenocarcinoma chemistry.chemical_compound Immunoglobulin Fab Fragments Mice Nuclear magnetic resonance Heterocyclic Compounds medicine Organometallic Compounds Tumor Cells Cultured Animals Radiology Nuclear Medicine and imaging Chelation Polylysine neoplasms Chromatography High Pressure Liquid medicine.diagnostic_test Chemistry business.industry Antibodies Monoclonal Magnetic resonance imaging General Medicine medicine.disease Magnetic Resonance Imaging Monoclonal Electrophoresis Polyacrylamide Gel Nuclear medicine business Colorectal Neoplasms Neoplasm Transplantation |
| Zdroj: | Investigative radiology. 33(10) |
| ISSN: | 0020-9996 |
| Popis: | Immunocontrast agents used for magnetic resonance imaging require antibodies that preserve the immunoreactivity while containing a high number of chelated paramagnetic ions.Anti-CEA F(ab')2 fragments were coupled to polylysine-Gd-DOTA and polylysine-Gd-DTPA. A paramagnetic load as high as n = 24 to 28 metal ions per antibody was reached.The immunoreactivity of the gadolinium (Gd)-labeled anti-CEA F(ab')2 immunoconjugates was 80% to 85%. Compared with that of commercial chelates, the relaxivity (R1) increase is as follows: Gd-DTPAGd-DOTAGd-H2OPL-Gd-DTPA24-28PL-Gd-DTPA24-28 F(ab')2PL-Gd-DOTA24-28PL-Gd-DOTA24-28 F(ab')2. 1H nuclear magnetic relaxation dispersion data of immunoconjugates showed that the high relaxivity enhancement was the result of a reduction of the molecular tumbling rate. Twenty-four hours after intravenous injection of 50 micrograms (1 mumol Gd/kg) of Gd-labeled immunoconjugates to nude mice grafted with human colorectal carcinoma LS 174T, the tumor uptake was 10% to 15%, resulting in an increase of R1 of up to 15% to 20% versus noninjected mice. No difference was found between PL-Gd-DTPA24-28 F(ab')2 and PL-Gd-DOTA24-28 F(ab')2 immunoconjugates for tumor, liver, and kidney uptake. A high signal intensity of tumor was observed in 50% of the tested mice. |
| Databáze: | OpenAIRE |
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