Initial clinical study of indium-111-labeled clone 110 anticarcinoembryonic antigen antibody in patients with colorectal cancer.
A murine monoclonal antibody directed against carcinoembryonic antigen (CEA) was labeled with indium-111 (111In) by means of a benzylisothiocyanate derivative of diethylenetriamine penta-acetic acid (DTPA) and used for clinical radioimmunodetection studies. Twenty-one patients having a history of surgically resected colorectal cancer and rising serum CEA levels suggestive of tumor recurrence were studied. Patients were infused over 20 minutes with 5, 10, or 20 mg of the monoclonal antibody labeled with 5 mCi of 111In. The mean radiochemical purity was greater than 96%. No toxicity was seen. The stability of the radiolabel on antibody in patient serum was demonstrated by high-performance liquid chromatography (HPLC), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) with autoradiography, and immunoprecipitation for up to 96 hours after infusion. Tumor sites were identified in 20 of 21 patients. Sites of antibody accumulation in 20 patients were confirmed as tumor either by resection at laparotomy (16 patients) or fine-needle biopsy (four patients). Nine patients who had the identified lesion resected or irradiated showed return of the serum CEA antigen level to normal or near normal values. In the absence of high levels of circulating CEA (greater than 500 ng/mL), the disappearance of radioactivity from patient serum demonstrated first order elimination kinetics, with a mean half-life of 38 hours. The serum half-life was not affected by the dose of antibody administered or by serum CEA titers below 500 ng/mL. Despite a mean liver uptake of 18% injected dose (ID) 24 hours after administration, hepatic metastases were easily visualized as areas of increased uptake of radioactivity. Radioimmunodetection of recurrent colorectal cancer, not detected by computed tomographic (CT) scans, appears achievable with this agent. This may allow successful clinical intervention in selected patients.
Griffin
T W
TW
Department of Medicine, University of Massachusetts Medical School, Worcester 01605-2397.
Brill
A B
AB
Stevens
S
S
Collins
J A
JA
Bokhari
F
F
Bushe
H
H
Stochl
M C
MC
Gionet
M
M
Rusckowski
M
M
Stroupe
S D
SD
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics; D000912:Antibodies, Neoplasm / Q000493:pharmacokinetics; D002272:Carcinoembryonic Antigen / Q000276:immunology*; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D007205:Indium Radioisotopes; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000556:secondary; D008297:Male; D008875:Middle Aged; D015899:Tomography, Emission-Computed, Single-Photon
D000911:Antibodies, Monoclonal; D000912:Antibodies, Neoplasm; D002272:Carcinoembryonic Antigen; D007205:Indium Radioisotopes