Localization and Imaging of Radiolabeled Monoclonal Antibodies against Colorectal Carcinoma in Tumor-bearing Nude Mice

Buchsbaum, Donald; Lloyd, Ricardo; Juni, Jack; Wollner, Ira; Brubaker, Pamela; Hanna, David; Spicker, Judith; Burns, Felissa; Steplewski, Zenon; Colcher, David; Schlom, Jeffrey; Buchegger, Franz; Mach, Jean-Pierre

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Articles| August 01 1988

Localization and Imaging of Radiolabeled Monoclonal Antibodies against Colorectal Carcinoma in Tumor-bearing Nude Mice^¹

Donald Buchsbaum;

Donald Buchsbaum

Departments of Radiation Oncology [D. B., P. B., D. H., J. Sp., F. Bur.], Pathology [R. L.], and Internal Medicine [J. J., I. W.], University of Michigan

,

Ann Arbor, Michigan 48109

; The

Wistar Institute

,

Philadelphia, Pennsylvania 19104 [Z. S.]

;

Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH

,

Bethesda, Maryland 20892 [D. C., J. Sc.]

; and

Institute of Biochemistry, University of Lausanne

,

CH-1066 Epalinges

,

Switzerland

[F. Buc., J.-P. M.]

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Ricardo Lloyd;

Ricardo Lloyd

Departments of Radiation Oncology [D. B., P. B., D. H., J. Sp., F. Bur.], Pathology [R. L.], and Internal Medicine [J. J., I. W.], University of Michigan

,

Ann Arbor, Michigan 48109

; The

Wistar Institute

,

Philadelphia, Pennsylvania 19104 [Z. S.]

;

Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH

,

Bethesda, Maryland 20892 [D. C., J. Sc.]

; and

Institute of Biochemistry, University of Lausanne

,

CH-1066 Epalinges

,

Switzerland

[F. Buc., J.-P. M.]

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Jack Juni;

Jack Juni

Departments of Radiation Oncology [D. B., P. B., D. H., J. Sp., F. Bur.], Pathology [R. L.], and Internal Medicine [J. J., I. W.], University of Michigan

,

Ann Arbor, Michigan 48109

; The

Wistar Institute

,

Philadelphia, Pennsylvania 19104 [Z. S.]

;

Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH

,

Bethesda, Maryland 20892 [D. C., J. Sc.]

; and

Institute of Biochemistry, University of Lausanne

,

CH-1066 Epalinges

,

Switzerland

[F. Buc., J.-P. M.]

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Ira Wollner;

Ira Wollner

Departments of Radiation Oncology [D. B., P. B., D. H., J. Sp., F. Bur.], Pathology [R. L.], and Internal Medicine [J. J., I. W.], University of Michigan

,

Ann Arbor, Michigan 48109

; The

Wistar Institute

,

Philadelphia, Pennsylvania 19104 [Z. S.]

;

Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH

,

Bethesda, Maryland 20892 [D. C., J. Sc.]

; and

Institute of Biochemistry, University of Lausanne

,

CH-1066 Epalinges

,

Switzerland

[F. Buc., J.-P. M.]

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Pamela Brubaker;

Pamela Brubaker

Departments of Radiation Oncology [D. B., P. B., D. H., J. Sp., F. Bur.], Pathology [R. L.], and Internal Medicine [J. J., I. W.], University of Michigan

,

Ann Arbor, Michigan 48109

; The

Wistar Institute

,

Philadelphia, Pennsylvania 19104 [Z. S.]

;

Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH

,

Bethesda, Maryland 20892 [D. C., J. Sc.]

; and

Institute of Biochemistry, University of Lausanne

,

CH-1066 Epalinges

,

Switzerland

[F. Buc., J.-P. M.]

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David Hanna;

David Hanna

Departments of Radiation Oncology [D. B., P. B., D. H., J. Sp., F. Bur.], Pathology [R. L.], and Internal Medicine [J. J., I. W.], University of Michigan

,

Ann Arbor, Michigan 48109

; The

Wistar Institute

,

Philadelphia, Pennsylvania 19104 [Z. S.]

;

Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH

,

Bethesda, Maryland 20892 [D. C., J. Sc.]

; and

Institute of Biochemistry, University of Lausanne

,

CH-1066 Epalinges

,

Switzerland

[F. Buc., J.-P. M.]

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Judith Spicker;

Judith Spicker

Departments of Radiation Oncology [D. B., P. B., D. H., J. Sp., F. Bur.], Pathology [R. L.], and Internal Medicine [J. J., I. W.], University of Michigan

,

Ann Arbor, Michigan 48109

; The

Wistar Institute

,

Philadelphia, Pennsylvania 19104 [Z. S.]

;

Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH

,

Bethesda, Maryland 20892 [D. C., J. Sc.]

; and

Institute of Biochemistry, University of Lausanne

,

CH-1066 Epalinges

,

Switzerland

[F. Buc., J.-P. M.]

Search for other works by this author on:

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Felissa Burns;

Felissa Burns

Departments of Radiation Oncology [D. B., P. B., D. H., J. Sp., F. Bur.], Pathology [R. L.], and Internal Medicine [J. J., I. W.], University of Michigan

,

Ann Arbor, Michigan 48109

; The

Wistar Institute

,

Philadelphia, Pennsylvania 19104 [Z. S.]

;

Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH

,

Bethesda, Maryland 20892 [D. C., J. Sc.]

; and

Institute of Biochemistry, University of Lausanne

,

CH-1066 Epalinges

,

Switzerland

[F. Buc., J.-P. M.]

Search for other works by this author on:

This Site

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Zenon Steplewski;

Zenon Steplewski

Departments of Radiation Oncology [D. B., P. B., D. H., J. Sp., F. Bur.], Pathology [R. L.], and Internal Medicine [J. J., I. W.], University of Michigan

,

Ann Arbor, Michigan 48109

; The

Wistar Institute

,

Philadelphia, Pennsylvania 19104 [Z. S.]

;

Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH

,

Bethesda, Maryland 20892 [D. C., J. Sc.]

; and

Institute of Biochemistry, University of Lausanne

,

CH-1066 Epalinges

,

Switzerland

[F. Buc., J.-P. M.]

Search for other works by this author on:

This Site

PubMed

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David Colcher;

David Colcher

Departments of Radiation Oncology [D. B., P. B., D. H., J. Sp., F. Bur.], Pathology [R. L.], and Internal Medicine [J. J., I. W.], University of Michigan

,

Ann Arbor, Michigan 48109

; The

Wistar Institute

,

Philadelphia, Pennsylvania 19104 [Z. S.]

;

Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH

,

Bethesda, Maryland 20892 [D. C., J. Sc.]

; and

Institute of Biochemistry, University of Lausanne

,

CH-1066 Epalinges

,

Switzerland

[F. Buc., J.-P. M.]

Search for other works by this author on:

This Site

PubMed

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Jeffrey Schlom;

Jeffrey Schlom

Departments of Radiation Oncology [D. B., P. B., D. H., J. Sp., F. Bur.], Pathology [R. L.], and Internal Medicine [J. J., I. W.], University of Michigan

,

Ann Arbor, Michigan 48109

; The

Wistar Institute

,

Philadelphia, Pennsylvania 19104 [Z. S.]

;

Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH

,

Bethesda, Maryland 20892 [D. C., J. Sc.]

; and

Institute of Biochemistry, University of Lausanne

,

CH-1066 Epalinges

,

Switzerland

[F. Buc., J.-P. M.]

Search for other works by this author on:

This Site

PubMed

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Franz Buchegger;

Franz Buchegger

Departments of Radiation Oncology [D. B., P. B., D. H., J. Sp., F. Bur.], Pathology [R. L.], and Internal Medicine [J. J., I. W.], University of Michigan

,

Ann Arbor, Michigan 48109

; The

Wistar Institute

,

Philadelphia, Pennsylvania 19104 [Z. S.]

;

Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH

,

Bethesda, Maryland 20892 [D. C., J. Sc.]

; and

Institute of Biochemistry, University of Lausanne

,

CH-1066 Epalinges

,

Switzerland

[F. Buc., J.-P. M.]

Search for other works by this author on:

This Site

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Jean-Pierre Mach

Departments of Radiation Oncology [D. B., P. B., D. H., J. Sp., F. Bur.], Pathology [R. L.], and Internal Medicine [J. J., I. W.], University of Michigan

,

Ann Arbor, Michigan 48109

; The

Wistar Institute

,

Philadelphia, Pennsylvania 19104 [Z. S.]

;

Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH

,

Bethesda, Maryland 20892 [D. C., J. Sc.]

; and

Institute of Biochemistry, University of Lausanne

,

CH-1066 Epalinges

,

Switzerland

[F. Buc., J.-P. M.]

Search for other works by this author on:

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Author & Article Information

²

To whom requests for reprints should be addressed, at Department of Radiation Oncology, University of Michigan, UH-Rm. B2C490/0010, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-0010.

Received: February 17 1988

Revision Received: April 28 1988

Accepted: May 04 1988

Online ISSN: 1538-7445

Print ISSN: 0008-5472

1988

American Association for Cancer Research, Inc.

Cancer Res (1988) 48 (15): 4324–4333.

Abstract

Four monoclonal antibodies (MoAbs) (35, 115, 17-1A, and B72.3) directed towards human carcinoma surface antigens have been studied in athymic nude mice with LS174T, CO112, or SW948 colon carcinoma xenografts or negative control melanoma (MEL-1), lymphoma (Namalwa), and breast (MCF-7) carcinoma xenografts to evaluate the effects of antigenic heterogeneity and time after administration on localization and imaging. ¹²⁵I-labeled 115 showed the highest uptake of any antibody in LS174T tumors. MoAbs 35 and B72.3 showed similar but lower levels of uptake in LS174T and CO112 tumors, but B72.3 concentrated less in SW948 tumors. 17-1A showed the highest degree of accumulation in SW948 tumor xenografts. No specific uptake of the four anti-carcinoma MoAbs was observed in MEL-1, Namalwa, or MCF-7 xenografts. The specificity of the in vivo tumor localization of the four anti-carcinoma MoAbs was confirmed by the low degree of accumulation of a control MoAb against influenza virus in LS174T tumors. Imaging studies with ¹³¹I-labeled colorectal cancer MoAbs showed specific uptake and retention in LS174T tumors, with progressive clearance from the whole body. The colorectal cancer MoAbs were compared for immunohistochemical binding against biopsies from patients with colorectal cancer and adjacent normal colonic tissue. Most colorectal cancer specimens showed moderate to strong staining with the four MoAbs. The percentage of positive cells varied within and between tumors demonstrating antigenic heterogeneity. Absent to slight focal staining was seen with normal colon tissue. B72.3 showed the highest degree of staining specificity. This study indicates a difference in the immunohistochemical binding of a panel of MoAbs against biopsies of colon adenocarcinoma and a dependence of in vivo localization on the human colon cancer cell line used as target. This has important implications for future clinical diagnostic and therapeutic studies.

¹

This investigation was supported by National Cancer Institute Grants CA44173 and CA43368 and a grant from the Medical Research Foundation, Inc., Atlanta, GA.

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1988

American Association for Cancer Research, Inc.

Localization and Imaging of Radiolabeled Monoclonal Antibodies against Colorectal Carcinoma in Tumor-bearing Nude Mice^¹

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Localization and Imaging of Radiolabeled Monoclonal Antibodies against Colorectal Carcinoma in Tumor-bearing Nude Mice1

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Localization and Imaging of Radiolabeled Monoclonal Antibodies against Colorectal Carcinoma in Tumor-bearing Nude Mice^¹