POLYLYSINE-GD-DTPA(N) AND POLYLYSINE-GD-DOTA(N) 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
C. Curtet et al., POLYLYSINE-GD-DTPA(N) AND POLYLYSINE-GD-DOTA(N) 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, Investigative radiology, 33(10), 1998, pp. 752-761
RATIONALE AND OBJECTIVES. Immunocontrast agents used for magnetic reso
nance imaging require antibodies that preserve the immunoreactivity wh
ile containing a high number of chelated paramagnetic ions. METHODS. A
nti-CEA F(ab')(2) fragments were coupled to polylysine-Gd-DOTA and pol
ylysine-Gd-DTPA, A paramagnetic load as high as n = 24 to 28 metal ion
s per antibody was reached. RESULTS. The immunoreactivity of the gadol
inium (Gd)-labeled anti-CEA F(ab'), immunoconjugates was 80% to 85%. C
ompared with that of commercial chelates, the relaxivity (R-1) increas
e is as follows: Gd-DTPA < Gd-DOTA < Gd-H2O < PL-Gd-DTPA(24-28) < PL-G
d-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 immunoconjugat
es showed that the high relaxivity enhancement was the result of a red
uction of the molecular tumbling rate, Twenty-four hours after intrave
nous injection of 50 mu g (1 mu mol Gd/kg) of Gd-labeled immunoconjuga
tes 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) immunoconjug
ates for tumor, liver, and kidney uptake, A high signal intensity of t
umor was observed in 50% of the tested mice.