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

M. Adel Bakir^*, Suzanne A. Eccles, John W. Babich, Nighat Aftab, Jennifer M. Styles, Christopher J. Dean and Robert J. Ott

Joint Department of Physics and Section of Immunology, Institute of Cancer Research and The Royal Marsden Hospital, Sutton, Surrey, United Kingdom

Correspondence: For reprints contact: Dr. Suzanne A. Eccles, Dept. of Immunology, Haddow Laboratories, Institute of Cancer Research, Downs Rd., Sutton, Surrey SM2 5NG, UK.

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. 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 elided after six days storage in plasma at 37°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/ICRMUP-PET camera. We suggest that ¹²⁴I-labeled ICR12 is a suitable agent to image and quantify immunolocalization in patients whose tumors over express the c-erbB2 proto-oncogene product.

FOOTNOTES

^* Present address: P.O. Box 11865, Damascus, Syria.

Present address: Dept of Radiology, Massachusetts General Hospital, Boston, MA.

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