Polylysine-Gd-DTPA: Relaxometry, Biodistribution, and Magnetic Resonance Imaging in Nude Mice Grafted With Human Colorectal Carcinoman: Relaxometry, Biodistribution, and Magnetic Resonance Imaging in Nude Mice Grafted With Human Colorectal Carcinoma and Polylysine-Gd-DOTA: Relaxometry, Biodistribution, and Magnetic Resonance Imaging in Nude Mice Grafted With Human Colorectal Carcinoman: Relaxometry, Biodistribution, and Magnetic Resonance Imaging in Nude Mice Grafted With Human Colorectal Carcinoma Coupled to Anti-CEA F(ab′): Relaxometry, Biodistribution, and Magnetic Resonance Imaging in Nude Mice Grafted With Human Colorectal Carcinoma2: Relaxometry, Biodistribution, and Magnetic Resonance Imaging in Nude Mice Grafted With Human Colorectal Carcinoma Fragments as Potential Immunocontrast Agents: Relaxometry, Biodistribution, and Magnetic Resonance Imaging in Nude Mice Grafted With Human Colorectal Carcinoma

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Abstract

RATIONALE AND OBJECTIVES.

Immunocontrast agents used for magnetic resonance imaging require antibodies that preserve the immunoreactivity while containing a high number of chelated paramagnetic ions.

METHODS.

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.

RESULTS.

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-DTPA < Gd-DOTA < Gd-H2O < PL-Gd-DTPA24-28 < PL-Gd-DTPA24-28 F(ab′)2 < PL-Gd-DOTA24-28 < PL-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 μg (1 μmol 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.

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