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.
OBJECTIVE
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 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.
Curtet
C
C
Laboratoire de Biophysique, INSERM Unité de Recherche, Institut de Biologie, Nantes, France.
Maton
F
F
Havet
T
T
Slinkin
M
M
Mishra
A
A
Chatal
J F
JF
Muller
R N
RN
D000230:Adenocarcinoma / Q000175:diagnosis*; D000818:Animals; D000911:Antibodies, Monoclonal; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000175:diagnosis*; D003287:Contrast Media / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D019786:Gadolinium DTPA / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000737:chemistry*; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D008279:Magnetic Resonance Imaging; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009942:Organometallic Compounds / Q000737:chemistry*; D011107:Polylysine / Q000737:chemistry; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D003287:Contrast Media; D006571:Heterocyclic Compounds; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D009942:Organometallic Compounds; D011107:Polylysine; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate; D019786:Gadolinium DTPA