title: 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.
abstract: 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.
authors.affiliation: Laboratoire de Biophysique, INSERM Unité de Recherche, Institut de Biologie, Nantes, France.
authors.forename: C
authors.initials: C
authors.lastname: Curtet
authors.forename: F
authors.initials: F
authors.lastname: Maton
authors.forename: T
authors.initials: T
authors.lastname: Havet
authors.forename: M
authors.initials: M
authors.lastname: Slinkin
authors.forename: A
authors.initials: A
authors.lastname: Mishra
authors.forename: J F
authors.initials: JF
authors.lastname: Chatal
authors.forename: R N
authors.initials: RN
authors.lastname: Muller
mesh_terms: 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
chemical_list: 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