RadioimmunoPET: Detection of colorectal carcinoma with positron-emitting copper-64-labeled monoclonal antibody

Detection of tumor foci may be improved by combining the selective tumor- targeting properties of a monoclonal antibody with the superior sensitivity and contrast resolution of PET. Methods: An anti-colorectal carcinoma monoclonal antibody (MAb 1A3) was labeled with ⁶⁴Cu, a positron-emitting radionuclide, by use of a bifunctional chelate (bromoacetamidobenzyl-TETA) and evaluated in 36 patients with suspected advanced primary or metastatic colorectal cancer. After radiopharmaceutical injection (5-20 mg protein, 10 mCi ⁶⁴Cu), PET was performed once or twice, 4 to 36 hr later. All patients had CT scans and 18 patients were also studied with [¹⁸F]fluorodeoxyglucose (FDG) PET. Results: In 29 patients, one or more tumor sites (n = 56) were proven, in 5 patients the absence of active tumor was confirmed and in the remaining 2, tumor status is not yet confirmed. Of the 56 confirmed tumor sites, 40 were detected by MAb-PET as foci of increased activity (sensitivity 71%). The positive predictive value of MAb-PET was excellent, ranging from 89% (40/45) to 96% (43/45), depending on the ultimate classification of three image-positive, but as yet unconfirmed tumor sites. Also, MAb-PET detected 11 new occult tumor sites, including 9 small abdominopelvic foci less than 2.0 cm in diameter that were not detected by CT or MRI. There were no complications, but significantly elevated HAMA titers were found in 28% of the 29 patients tested I to 12 mo after injection. There was no apparent dose-related effect from 5 to 20 mg MAb 1A3. Conclusion: These Phase 1/11 results suggest that PET with radiolabeled MAbs (radioimmunoPET) may have important applications in clinical oncology, particularly for detecting smaller colorectal tumor foci in the abdomen or pelvis and for determining accurate dosimetry.