Improved tumor localization with increasing dose of indium-111-labeled anti-carcinoembryonic antigen monoclonal antibody ZCE-025 in metastatic colorectal cancer
Monoclonal antibodies (MoAbs) against carcinoembryonic antigen (CEA) react with human colorectal cancer cells, and when labeled with a gamma-emitting radioisotope, may help to localize known and occult metastatic disease. We tested ZCE-025, a high-affinity immune gamma globulin1 (IgG1) MoAb anti-CEA that does not react with normal granulocyte glycoproteins in a phase I/II trial to determine the reagent's toxicity and its maximum efficacy in detecting metastatic colorectal cancer. Increasing doses of unlabeled ZCE-025 were mixed with 1 mg of Indium-111 (111In)-radiolabeled MoAb and administered intravenously (IV) to 34 patients who had metastatic colorectal cancer. Planar nuclear or single photon emission computed tomographic (SPECT) scans were performed 48 to 72 and 120 to 144 hours later. Total dose of MoAb and scanning sensitivity (number of imaged lesions/number of known lesions) were correlated up to 80 mg. At doses of 2.5 to 20 mg, a mean of 22% of the lesions were imaged; at 40 mg, 77% were imaged (P less than .01). Liver metastases were detected as areas of increased activity (hot) at the 40 mg dose but showed decreased MoAb uptake at lower doses. At the 40 mg dose normal liver parenchymal uptake of the labeled MoAb was lower with respect to blood pool compared with the other doses. At 80 mg, however, sensitivity of detection declined to 21%. One milligram of 111In-labeled ZCE-025 antibody coinfused with 39 mg of unlabeled antibody appeared optimal for detecting metastatic colorectal cancer, particularly in the liver. Although the exact mechanism(s) for this dose effect is currently unknown, a partial blocking effect of unlabeled antibody with a change in MoAb biodistribution may be occurring.
- Research Organization:
- Univ. of Texas, Anderson Hospital and Tumor Institute, Houston (USA)
- OSTI ID:
- 6735196
- Journal Information:
- J. Clin. Oncol.; (United States), Journal Name: J. Clin. Oncol.; (United States) Vol. 6:8; ISSN JCOND
- Country of Publication:
- United States
- Language:
- English
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62 RADIOLOGY AND NUCLEAR MEDICINE
ANTIBODIES
ANTIGENS
BETA DECAY RADIOISOTOPES
BODY
CARCINOEMBRYONIC ANTIGEN
COMPUTERIZED TOMOGRAPHY
COUNTING TECHNIQUES
DAYS LIVING RADIOISOTOPES
DIAGNOSIS
DIAGNOSTIC TECHNIQUES
DIGESTIVE SYSTEM
DISEASES
ELECTRON CAPTURE RADIOISOTOPES
EMISSION COMPUTED TOMOGRAPHY
GASTROINTESTINAL TRACT
GLANDS
INDIUM 111
INDIUM ISOTOPES
INTERMEDIATE MASS NUCLEI
INTESTINES
ISOMERIC TRANSITION ISOTOPES
ISOTOPES
LABELLING
LARGE INTESTINE
LIVER
METASTASES
MINUTES LIVING RADIOISOTOPES
MONOCLONAL ANTIBODIES
NEOPLASMS
NUCLEI
ODD-EVEN NUCLEI
ORGANS
RADIOISOTOPE SCANNING
RADIOISOTOPES
RECTUM
SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY
TOMOGRAPHY