c-erbB2 Protein Overexpression in Breast Cancer as a Target for PET Using Iodine-124-Labeled Monoclonal Antibodies

ICR 12, one of a panel of rat monoclonal antibodies recognizing the external domain of the human c-erb B2 proto-oncogene product, (Styles, 1990) was chosen as a candidate for radiolabeling with 124I for positron emission tomography of selected patients with breast cancer. By using N-bromosuccinimide...

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Veröffentlicht in:The Journal of nuclear medicine (1978) 1992-12, Vol.33 (12), p.2154-2160
Hauptverfasser: Bakir, M. Adel, Eccles, Suzanne A, Babich, John W, Aftab, Nighat, Styles, Jennifer M, Dean, Christopher J, Ott, Robert J
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container_issue 12
container_start_page 2154
container_title The Journal of nuclear medicine (1978)
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creator Bakir, M. Adel
Eccles, Suzanne A
Babich, John W
Aftab, Nighat
Styles, Jennifer M
Dean, Christopher J
Ott, Robert J
description ICR 12, one of a panel of rat monoclonal antibodies recognizing the external domain of the human c-erb B2 proto-oncogene product, (Styles, 1990) was chosen as a candidate for radiolabeling with 124I for positron emission tomography of selected patients with breast cancer. By using N-bromosuccinimide (NBS), optimal labeling conditions were established using 125I. The labeling efficiency was determined using instant thin-layer chromatography (ITLC) and gel filtration (HPLC). The antibody was then labeled with the positron emitter 124I, and a labeling efficiency of 96% and immunoreactivity of 80%-90% was obtained. The product was stable, with less than 5% of the radiolabel being eluted after six days storage in plasma at 37 degrees C. Immunolocalization studies were performed in athymic mice bearing human breast carcinoma xenografts overexpressing the c-erb B2 gene product using as controls 125I labeled isotype-matched rat antibody, and antigen-negative tumors. Good uptake of 124I-labeled ICR12 was obtained in c-erb B2 expressing tumors (up to 12% injected dose per gram at intervals up to 120 hr), with localization indices of 3.4-6.2. Tumor xenografts of 6 mm diameter were successfully imaged with high resolution at 24, 48 and 120 hr using the RMH/ICR MUP-PET camera. We suggest that 124I-labeled ICR12 is a suitable agent to image and quantify immunolocalization in patients whose tumors overexpress the c-erb B2 proto-oncogene product.
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The product was stable, with less than 5% of the radiolabel being eluted after six days storage in plasma at 37 degrees C. Immunolocalization studies were performed in athymic mice bearing human breast carcinoma xenografts overexpressing the c-erb B2 gene product using as controls 125I labeled isotype-matched rat antibody, and antigen-negative tumors. Good uptake of 124I-labeled ICR12 was obtained in c-erb B2 expressing tumors (up to 12% injected dose per gram at intervals up to 120 hr), with localization indices of 3.4-6.2. Tumor xenografts of 6 mm diameter were successfully imaged with high resolution at 24, 48 and 120 hr using the RMH/ICR MUP-PET camera. 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Adel</creatorcontrib><creatorcontrib>Eccles, Suzanne A</creatorcontrib><creatorcontrib>Babich, John W</creatorcontrib><creatorcontrib>Aftab, Nighat</creatorcontrib><creatorcontrib>Styles, Jennifer M</creatorcontrib><creatorcontrib>Dean, Christopher J</creatorcontrib><creatorcontrib>Ott, Robert J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>The Journal of nuclear medicine (1978)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bakir, M. Adel</au><au>Eccles, Suzanne A</au><au>Babich, John W</au><au>Aftab, Nighat</au><au>Styles, Jennifer M</au><au>Dean, Christopher J</au><au>Ott, Robert J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>c-erbB2 Protein Overexpression in Breast Cancer as a Target for PET Using Iodine-124-Labeled Monoclonal Antibodies</atitle><jtitle>The Journal of nuclear medicine (1978)</jtitle><addtitle>J Nucl Med</addtitle><date>1992-12-01</date><risdate>1992</risdate><volume>33</volume><issue>12</issue><spage>2154</spage><epage>2160</epage><pages>2154-2160</pages><issn>0161-5505</issn><eissn>1535-5667</eissn><abstract>ICR 12, one of a panel of rat monoclonal antibodies recognizing the external domain of the human c-erb B2 proto-oncogene product, (Styles, 1990) was chosen as a candidate for radiolabeling with 124I for positron emission tomography of selected patients with breast cancer. 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subjects Animals
Antibodies, Monoclonal
Breast Neoplasms - diagnostic imaging
Breast Neoplasms - genetics
Breast Neoplasms - metabolism
Humans
Iodine Radioisotopes - pharmacokinetics
Mice
Mice, Nude
Proto-Oncogene Proteins - metabolism
Radioimmunodetection - methods
Rats
Tomography, Emission-Computed
Transplantation, Heterologous
title c-erbB2 Protein Overexpression in Breast Cancer as a Target for PET Using Iodine-124-Labeled Monoclonal Antibodies
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