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Clinical Studies of Cancer Radioimmunodetection with Carcinoembryonic Antigen Monoclonal Antibody Fragments Labeled with ¹²³I or ^99mTc¹

Center for Molecular Medicine and Immunology and Department of Radiology, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey 07103; Morristown Memorial Hospital, Morristown, New Jersey 07960; and Immunomedics, Inc., Warren, New Jersey 07060

Seventy-three patients with diverse cancers containing carcinoembryonic antigen received ¹²³I-labeled anti-carcinoembryonic antigen monoclonal antibody F(ab')₂ fragment [38 patients], ^99mTc-labeled anticarcinoembryonic antigen monoclonal antibody Fab' fragment [23 patients], or both reagents at different times [6 patients] for evaluation of antibody targeting and imaging [radioimmunodetection (RAID)], using planar and single-photon emission computed tomography. The results indicated that antibody fragments are preferred for early tumor imaging (within 24 h). Rapid targeting and clearance from blood and normal organs of the antibody fragments (blood median t_1/2 elimination of 26.5 and 13.2 h for the F(ab')₂ and Fab' fragments, respectively) permitted the use of short-lived radionuclides, such as ¹²³I (13.3 h) and ^99mTc (6 h), and confirmed that selective antibody accretion in tumors occurred very soon after administration, such as between 2 and 5 h. Scan interpretations at 24 h for the ¹²³I-labeled F(ab')₂ and at 2–5 h for the ^99mTc-labeled Fab' revealed overall sensitivities, on a tumor site basis, of 95.9 and 94.9%, respectively. On a site basis, the overall accuracies were 94.2 and 93.8% for the ¹²³I and ^99mTc immunoconjugates, respectively. In the 6 patients studied with both radioimmunoconjugates, a high concordance in detection was found. Both imaging agents also revealed a high number of putatively new tumor sites not disclosed by other radiological methods at the time of the RAID studies, of which 40.0 and 20.5% were subsequently confirmed as tumor for the ¹²³I and ^99mTc agents, respectively, within an 11-month follow-up period. This represented 24 proven occult tumor sites in 19 patients given the ¹²³I-immunoconjugate and 16 proven occult tumor sites in 9 patients receiving the ^99mTc agent. The new lesions were found up to 17 and 7 months earlier for ¹²³I-RAID and ^99mTc-RAID, respectively, than with other detection methods. The smallest tumors identified were below 0.5 cm, especially with the ^99mTc immunoconjugate and single-photon emission computed tomography imaging.

The findings of this study confirm previous evidence that RAID is a safe and a potentially useful new method of cancer detection. Despite the excellent results with the ¹²³I-F(ab')₂ antibody fragment, its poor availability and high cost limit its clinical use. Therefore, the ^99mTc agent, which is made by an instant, 1-step, 1-vial, direct labeling method, appears to be the method of choice for rapid and accurate detection of cancer by RAID.