The use of radiolabelled monoclonal antibodies in the diagnosis of colorectal carcinomas

The development of monoclonal antibodies (mAbs) using the hybridoma technology has led to new approaches for imaging cancer patients. mAbs against carcinoembryonic antigen (CEA) or TAG-72, two tumour-associated antigens expressed by the vast majority of colorectal adenocarcinomas, have been successfully conjugated with various radionuclides such as I-131, I-123, Tc-99m and In-111. Clinical trials have demonstrated the relative safety of these molecules as well as their unique ability to identify lesions not detected by conventional radiographic imaging modalities. In-111 satumomab pendetide was the first clinically approved murine mAb conjugate for imaging colorectal and ovarian carcinomas. Clinical experience suggests a useful role for In-111 satumomab pendetide in the post-operative evaluation of patients with suspected recurrent colorectal cancer. as well as the potential for altering patient management and possibly a reduction in the costs associated with the work-up and evaluation of patients with occult recurrent colorectal carcinomas. The routine clinical application of these murine-based mAbs is limited by the induction of bust immune responses, notably the formation of human anti-mouse antibodies. These have been shown to significantly alter the biodistribution and pharmacokinetics of In-111 satumomab pendetide, leading to a reduction in tumour targeting effectiveness. Alternatives such as the development of chimaeric antibodies or entirely human mAbs, or the use of the nonimmunogenic portion of the mAb, i.e. Fab' fragments, have been proposed and are currently under investigation. Tc-99m arcitumomab, an Fab' fragment of IMMU-4, an anti-CEA monoclonal antibody, has recently been approved for imaging in colorectal cancer.