OBJECTIVE This study was designed to evaluate a new anticolorectal carcinoma monoclonal antibody (1A3), conjugated with the bifunctional chelating agent N,N'-bis(2-hydroxybenzyl)1(4-bromoacetamidobenzyl)1,2-ethylenediam ine-N,N'- diacetic acid and labeled with indium-111, in a Phase I/II study involving 38 patients with localized or advanced colorectal cancer. METHODS Patients were injected with indium-111-N,N'-bis(2-hydroxybenzyl) 1(4-bromoacetamidobenzyl)1,2-ethylenediamine-N,N'-diacetic acid-monoclonal antibody 1A3 (1-50 mg, 1-5 mCi) and imaged at two or three sessions one to five days later. Scintigraphic findings were compared with radiologic, pathologic, surgical, and other clinical findings to assess the accuracy of radioimmunoscintigraphy. RESULTS At least one known tumor site was clearly defined by planar scintigraphy in 29 (76 percent) patients. Increased radioactivity was seen in 40 of 63 known tumor sites (37/43 abdominal-pelvic, 3/15 hepatic, and 0/5 pulmonary sites) without any apparent dose-related effects. Nineteen previously undetected sites were considered positive by imaging, and, of these, six were biopsy-proven tumor sites, four were probable tumor sites, three were definitely false positive sites, and six were probable false positive sites. Radioimmunoscintigraphy detected proven tumor in 15 of 16 patients with negative or equivocal computed tomography results. Of of the 28 patients with rectosigmoid cancer, 25 (89 percent) had positive studies with 34 of 47 tumor sites showing definite uptake on the scintigrams. This included 3 of 9 hepatic metastases. The only adverse reaction occurred in one patient who developed transient hives. Human anti-mouse antibody responses occurred in approximately one-half of the patients injected with doses of 10 or 50 mg. CONCLUSIONS This study shows that radioimmunoscintigraphy with this indium-111-labeled monoclonal antibody is safe, it can detect most nonhepatic abdominal-pelvic tumors with a positive predictive value of 83 (44/53) percent, and it should prove to be useful, particularly in the diagnosis of recurrent rectal carcinoma.