Radioimmunodetection of colorectal carcinoma using technetium-99m-labeled fab′ fragments of the immu-4 anti-carcinoembryonic antigen monoclonal antibody

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Abstract
Radioimmunodetection of cancer using monoclonal antibody fragments offers certain potential advantages over that with whole monoclonal antibodies, including the ability to image early (i.e., to provide images at an early time after injection of the radioantibody) while minimizing the incidence of human anti-mouse antibody response. This paper reports a prospective trial comparing radioimmunodetection with IMMU-4 (a murine anti-CEA monoclonal antibody) 99mTc-labeled Fab' fragments to conventional imaging in 35 colorectal cancer patients. All patients were investigated by conventional diagnostic methods (CDM) within 4 weeks of radioimmunodetection. Surgical corroboration of findings was obtained in 26 patients (15 with evidence of disease on CDM [CDM+] and 11 with abnormal serum CEA [CDM-] as the only evidence for recurrence). After 1 mg IMMU-4 99mTc-Fab' was injected (19.3 mCi on average), patients underwent planar/SPECT radioimmunodetection 2-5 hours later and planar radioimmunodetection 18-24 hours later. Three patients underwent a second radioimmunodetection study 16, 20 and 23 months after the first. Radioimmunodetection was superior to CDM, accurately predicting disease distribution in six nonsurgical and ten CDM+ surgical patients, and was complementary to computed tomography in two nonsurgical and two CDM+ surgical patients. Radioimmunodetection would have directed or changed management decisions in 6 of the 15 (40%) CDM+ surgical patients. Radioimmunodetection correctly identified all recurrent tumor in 8 of 11 CDM- surgical patients and was negative in one patient with cirrhosis and no recurrence, representing a potential clinical benefit of 82%. Analyzed on a regional basis, radioimmunodetection was found to be superior to CDM in extrahepatic abdomen and pelvis imaging and was complementary to (although not as accurate as) CDM in the liver. Human anti-mouse antibody did not develop in any of the patients, including three who were injected twice. IMMU-4 99mTc-Fab' radioimmunodetection shows promise as a clinically useful diagnostic tool in patients with colorectal cancer, detecting disease often missed by conventional imaging. IMMU-4 99mTc-Fab' may prove useful for serial radioimmunodetection studies, because human anti-mouse antibody response does not appear to be a problem with this radioimmunoconjugate. It also has the advantage of permitting same-day imaging.