BIODISTRIBUTION AND LOCALIZATION OF RADIOLABELED NR-LU-10 FAB FRAGMENT IN HUMAN BREAST-CANCER XENOGRAFTS

Radioimmunodetection, which takes advantage of tumor-specific or tumor -associated radiolabeled monoclonal antibodies or other biologic molec ules to diagnose the extent of disease in cancer patients, has been of limited use in studies to date in patients with breast cancer. The di fficulty is in finding an antibody that is both sensitive and specific enough to localize in breast tumors. This study undertook immunohisto chemical and in vivo evaluation of tumor localization and biodistribut ion of NR-LU-10 Fab (antibody fragment) in breast tumors to determine its ability to bind selectively to malignant tissue. NR-LU-10 Fab reco gnizes a pancarcinoma glycoprotein antigen found on tumors of epitheli al cell origin. NR LU-IO Fab reacted with 6/6 (100%) breast cancer cel l lines and 14/16 (87.5%) breast tumors with varying degrees of immuno staining intensities. Athymic mice bearing ZR-75-1 breast cancer xenog rafts were injected with I-125-labeled NR-LU-10 Fab (12 mu g/5 mu Ci) and sacrificed at fixed time intervals. These studies demonstrated the highest tumor uptake of labeled Fab at 12 h postinjection (4.58 +/- 1 .59% of injected dose/gram [% ID/g] of tissue); this gradually decreas ed to 0.13 +/- 0.05% ID/g of tissue by 72 h postinjection of the radio labeled Fab, Biolocalization to normal tissues was as predicted for a Fab fragment; i.e., initially high in clearance organs (kidney), follo wed by rapid clearance over the 72-h test period. NR-LU-10 Fab display s adequate breast tumor localization with minimal biolocalization to n ormal tissues, thus supporting its potential use in radioimmunoscintig raphy and the RIGS(R) system (radioimmunoguided surgery). (C) 1998 Els evier Science Inc.