THE PHARMACOKINETICS AND DIAGNOSTIC-ACCURACY OF LOW-DOSE INDIUM 111-LABELED B72.3 (CYT-103) IN PATIENTS WITH METASTATIC BREAST-CANCER

The purpose of this study was to determine the ability of an In-111-la beled conjugate of B72.3 (CYT-103) to detect sites of proven or suspec ted local and metastatic foci of breast cancer. The safety, pharmacoki netics and human anti-mouse antibody response to this immunoconjugate were also examined. 22 subjects with suspected metastatic breast cance r were evaluated with 0.2 mg of In-111 labeled CYT-103 using planar im aging and single photon emission tomography between 2 and 5 days follo wing injection. Pharmacokinetics were determined by assaying urine (n= 5) and by blood sampling (n=6) over 3 days. Assay for human anti-mouse antibody was performed in all subjects before and from 1 to 6 months after injection. Conventional imaging modalities were used as the ''go ld-standard'' for comparison with CYT-103 findings in all subjects exc ept in the one subject that had biopsy results available. No adverse c linical effects were seen following CYT- 103 administration. Mean plas ma half-life clearance was 44.7 hours (range 27.7-61.9). Mean (as % in jected dose +/- SD) cumulative urinary excretion at 2, 24, 48 and 72 h ours was 1.4 +/- 0.7%, 4.8 +/- 0.9%, 7.4 +/- 1.5% and 10.1 +/- 2.2% re spectively. Human anti-mouse antibody was detected in 4 of 22 subjects . CYT- 103 imaging detected the presence of disease in 22 of 56 confir med lesions in the subject population (lesion sensitivity = 39%) and d etected at least one lesion in 10 of the 20 subjects who had metastati c disease (subject sensitivity = 50%). Immunohistology was not perform ed tissue samples, so in vitro antigen expression was not known. These preliminary results suggest that, while safe, In-111-labeled CYT-103 is a relatively insensitive method for detecting sites of metastatic b reast cancer. The pharmacokinetic results and human antimouse antibody response was similar to the reported results in subjects with other t ypes of cancer.