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

Citation
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
Citations number
24
Categorie Soggetti
Radiology,Nuclear Medicine & Medical Imaging
Journal title
ISSN journal
00209996
Volume
33
Issue
10
Year of publication
1998
Pages
752 - 761
Database
ISI
SICI code
0020-9996(1998)33:10<752:PAPCTA>2.0.ZU;2-V
Abstract
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.