INITIAL CLINICAL-EVALUATION OF RADIOLABELED MX-DTPA HUMANIZED BRE-3 ANTIBODY IN PATIENTS WITH ADVANCED BREAST-CANCER

To evaluate radiometal-labeled humanized BrE-3 (huBrE-3) monoclonal an tibody as a radioimmunolocalization and therapeutic agent in breast ca ncer patients, tumor localization, pharmacokinetics, radiation dosimet ry, and immunogenicity of In-111-labeled combined 1-p-isothiocyanatobe nzyl 3-methyl- and 1-p-isothiocyanatobenzyl 4-methyl-diethylenetriamin e pentaacetic acid (MX-DTPA) huBrE-3 were studied. Seven women with Br E-3 antigen-positive, metastatic breast carcinoma underwent In-111 huB rE-3 infusion (5 mCi; 50 mg), followed by serial gamma camera imaging and plasma sampling. Region of interest analysis of images was used to make radiation absorbed dose estimates for In-111 huBrE-3, Data were extrapolated to Y-90 huBrE-3, Human anti-human antibody (HAHA) respons e was measured in serum samples obtained up to 3 months;after infusion . Patients tolerated infusions well. Seventy-six percent of 105 known sites of disease were identified on planar and single-photon emission computed tomography scans. For six of seven patients, a biexponential model fit the plasma time-activity curve best with an average T-1/2 al pha = 10.6 +/- 8.5 (SD)h and average T-1/2 beta = 114.2 +/- 39.2 h. Ra diation absorbed dose estimates for 111In huBrE-3 for whole body avera ged 0.53 +/- .08 rads/mCi. Dose estimates for Y-90 huBrE-3 for marrow averaged 8.4 +/- 11.9 rads/mCi, and for tumors, 70 +/- 31.5 rads/mCi. Liver radioactivity uptake averaged 19.7 +/- 8.8% injected dose at 24 h after infusion, translating irate an average radiation absorbed dose 21.1 +/- 12 rads/Y-90 mCi administered. Only one of seven patients de monstrated a low level of HAHA response. Although the plasma half-live s are longer and marrow dose higher for radiolabeled huBrE-3 compared with the murine construct, the excellent tumor localization, good tumo r dosimetry, and low immunogenicity support the use of Y-90-huBrE-3 an tibody for radioimmunotherapy of breast cancer.