IMMUNOSCINTIGRAPHY OF HUMAN MAMMARY-CARCINOMA XENOGRAFTS USING MONOCLONAL-ANTIBODIES 12H12 AND BM-2 LABELED WITH TE-99M AND RADIOIODINE

For immunoscintigraphic localization of human breast cancer two monocl onal antibodies (mabs) 12H12 (immunoglobulin G1) and BM-2 (immunoglobu lin G3) were developed. The mabs, directed against two different epito pes on the mucin glycoprotein TAG-12, showed reactivity with 96% of al l primary mammary carcinomas. The antibodies were labeled with either I-125 or I-131. In addition, 12H12 was directly labeled with Tc-99m ac cording to the method of Schwarz and Steinstrasser (A. Schwarz and A. Steinstrasser, J. Nucl. Med., 28: 721, 1987). Biodistribution was meas ured in female nude mice bearing the human mammary carcinoma SF-15. Bo th 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. Tc-99m-Labeling of the mab 12H12 led to an enhanced tumor up take of 10.5 and 14% injected dose/g at 6 and 24 h postinjection, resp ectively, and to significantly accelerated blood clearance of radioact ivity. Similar results were obtained with a second mammary tumor (AR-1 ), while an endometrial tumor (EK-3) showed a 3-fold lower accumulatio n of radioactivity and no difference in uptake of radioiodinated and T c-99m-labeled 12H12. Scintigraphic imaging of tumor-bearing nude mice with the Tc-99m 12H12 at 24 h postinjection clearly demonstrated a dia gnostic potential of the new mab for tumor localization and staging.