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Immunoscintigraphy of Human Mammary Carcinoma Xenografts Using Monoclonal Antibodies 12H12 and BM-2 Labeled with ^99mTc and Radioiodine

Department of Gynaecological Oncology, University Hospital Heidelberg [T. H. B., S. K., G. B.]; Department of Diagnostic and Therapeutic Radiology [J. S., R. M., G. K.], German Cancer Research Center, Heidelberg; and Department of Nuclear Medicine [R. P. B., S. A.], University Medical Center, Frankfurt/Main, Germany

For immunoscintigraphic localization of human breast cancer two monoclonal antibodies (mabs) 12H12 (immunoglobulin G1) and BM-2 (immunoglobulin G3) were developed. The mabs, directed against two different epitopes on the mucin glycoprotein TAG-12, showed reactivity with 96% of all primary mammary carcinomas. The antibodies were labeled with either ¹²⁵I or ¹³¹I. In addition, 12H12 was directly labeled with ^99mTc according to the method of Schwarz and Steinsträsser (A. Schwarz and A. Steinstrasser, J. Nucl. Med., 28: 721, 1987). Biodistribution was measured in female nude mice bearing the human mammary carcinoma SF-15. Both radioiodinated mabs showed similar biodistribution with fast tumor uptake (8.5% injected dose/g at 6 h postinjection), which increased to 10–11% injected dose/g at 24 h and subsequently remained constant up to 120 h. ^99mTc-Labeling of the mab 12H12 led to an enhanced tumor uptake of 10.5 and 14% injected dose/g at 6 and 24 h postinjection, respectively, and to significantly accelerated blood clearance of radioactivity. Similar results were obtained with a second mammary tumor (AR-1), while an endometrial tumor (EK-3) showed a 3-fold lower accumulation of radioactivity and no difference in uptake of radioiodinated and ^99mTc-labeled 12H12. Scintigraphic imaging of tumor-bearing nude mice with the ^99mTc 12H12 at 24 h postinjection clearly demonstrated a diagnostic potential of the new mab for tumor localization and staging.

¹ To whom requests for reprints should be addressed, at Onkologisches Labor, Universitätsfrauenklinik, Voßstr. 7, 69115 Heidelberg, Germany.

Received 10/26/93. Accepted 6/ 1/94.

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