Improved tumor localization with increasing dose of Indium-111-labeled anti-carcinoembryonic antigen monoclonal antibody ZCE-025 in metastatic colorectal cancer

Y. Z. Patt, L. M. Lamki, T. P. Haynie, M. W. Unger, M. G. Rosenblum, A. Shirkhoda, J. L. Murray

Research output: Contribution to journalArticle

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Abstract

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 (Hybritech, Inc, San Diego), 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 50 mg, 77% were imaged (P < .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.

Original languageEnglish
Pages (from-to)1220-1230
Number of pages11
JournalJournal of Clinical Oncology
Volume6
Issue number8
Publication statusPublished - 1988

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Indium
Carcinoembryonic Antigen
Colorectal Neoplasms
Antibodies
Liver
Neoplasms
Photons
Granulocytes
Radioisotopes
Glycoproteins
Monoclonal Antibodies
Neoplasm Metastasis
monoclonal antibody ZCE 025

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Improved tumor localization with increasing dose of Indium-111-labeled anti-carcinoembryonic antigen monoclonal antibody ZCE-025 in metastatic colorectal cancer. / Patt, Y. Z.; Lamki, L. M.; Haynie, T. P.; Unger, M. W.; Rosenblum, M. G.; Shirkhoda, A.; Murray, J. L.

In: Journal of Clinical Oncology, Vol. 6, No. 8, 1988, p. 1220-1230.

Research output: Contribution to journalArticle

Patt, Y. Z. ; Lamki, L. M. ; Haynie, T. P. ; Unger, M. W. ; Rosenblum, M. G. ; Shirkhoda, A. ; Murray, J. L. / Improved tumor localization with increasing dose of Indium-111-labeled anti-carcinoembryonic antigen monoclonal antibody ZCE-025 in metastatic colorectal cancer. In: Journal of Clinical Oncology. 1988 ; Vol. 6, No. 8. pp. 1220-1230.
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abstract = "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 (Hybritech, Inc, San Diego), 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 50 mg, 77{\%} were imaged (P < .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.",
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