Magnetic resonance imaging studies on nude mice grafted with colorectal adenocarcinoma using gadolinium-labeled monoclonal antibody.

ABSTRACT

A monoclonal antibody (Ab) 19.9 specific for colorectal carcinoma was labeled with a high number of gadolinium (Gd) atoms for its potential application as a contrast agent in magnetic resonance imaging (MRI). The DTPA was conjugated to 19.9 Ab via the bicyclic DTPA anhydride method (c. DTPA) using c. DTPA/Ab molar ratios between 5 and 150. The aggregates present in great amount at high c. DTPA/Ab ratios were systematically removed. Then the exact number of DTPA effectively conjugated, the immunoreactivity of the resulting 111In-DTPA-Ab were measured. The number of DTPA conjugated per antibody can be increased 20 to 25 with only a little loss of immunoreactivity. The 19.9 antibody conjugated with 16 and 25 DTPA was labeled with 153GdCl3 for pharmacokinetic studies on xenografted nude mice and with nonradioactive gadolinium to measure ex vivo the effect on the relaxation time T1 of the tumor. We found a 15 to 20% decrease of T1 on the tumor. In vivo experiments using a Bruker system and the same animal model showed a difference in the tumor contrast after the injection of 2 mg of Gd-labeled Ab.