A Thousand Points of Light or Just Dim Bulbs? Radiolabeled Antibodies and Colorectal Cancer Imaging

Abstract

Radioimmunoscintigraphy (RIS) is coming into its own as an imaging modality in clinical oncology. Early experience with indium-III-labeled intact murine monoclonal antibodies (MoAbs) in colorectal cancer suggested that RIS images hepatic metastases poorly. Moreover, an antimurine immune response was frequently provoked, precluding multiple follow-up RIS studies in individual patients due to reticu-loendothelial sequestration of the radioimmunoconjugate before tumor targeting could occur. Recent trials of technetium-99m- labeled antibody fragments and human MoAbs have demonstrated significant improvement in imaging efficacy, and repeated or serial imaging is possible because of the absence of associated immunoge-nicity. RIS is demonstrably more sensitive than conventional diagnostic modalities (CDM) such as computed tomography (CT)for detection of extrahepatic abdominal and pelvic colorectal carcinoma and is complementary to CDM in imaging liver metastases. In a surgical decision-making analysis comparing CT, RIS (IMMU-4 99mTc-Fab′; CEA-Scan®), and CT plus RIS in patients with recurrent or metastatic colorectal cancer, CT plus RIS improved correct prediction of resectability by 40% and correct prediction of unresectability by 100% compared with CT alone. At the present time, RIS used in combination with CDM contributes an incremental improvement in diagnostic accuracy in colorectal cancer patients with known or suspected recurrent disease. Basic and clinical research currently in progress promises to yield agents and methods that provide rapid high-resolution imaging, high tumor-to-background ratios in all organs at risk for tumor recurrence or metastasis, negligible immuno genicity and toxicity, and a signficant further improvement in the accuracy of clinical decision making in oncology patients.