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

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'), immunoconjugates was 80% to 85%. Compared with that of commercial chelates, the relaxivity (R-1) increase is as follows: Gd-DTPA < Gd-DOTA < Gd-H2O < PL-Gd-DTPA(24-28) < PL-Gd-DTPA(24-28) F(ab')(2) < PL-Gd-DOTA(24-28) < PL-Gd-DOTA(24-28) F(ab')(2). H-1 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 mu g (1 mu mol 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 R-1 of up to 15% to 20% versus noninjected mice. No difference was found between PL-Gd-DTPA(24-28) F(ab')(2) and PL-Gd-DOTA(24-28) F(ab')(2) immunoconjugates for tumor, liver, and kidney uptake, A high signal intensity of tumor was observed in 50% of the tested mice.