(67)Copper-2-iminothiolane-6-[p-(bromoacetamido)benzyl]-TETA Lym-1 for radioimmunotherapy of non-Hodgkin's lymphoma

Copper-67 ((CU)-C-67) has ideal properties for radioimmunotherapy. The 62-h half-life is similar to the residence time of antibodies in tumor, and the therapeutic beta emission of (CU)-C-67 is comparable to that of I-131. (CU )-C-67, however, has gamma emissions similar to (99m)technetium that are fa vorable for imaging. The macrocyclic chelating agent 1,4,7,11-tetraazacyclo tetradecane-N,N',N'',N'''-tetraacetic acid (TETA) binds 67CU tightly and se lectively, facilitating linkage to Lym-1, a mouse monoclonal antibody that preferentially targets malignant lymphocytes. The safety, efficacy, and pra cticality of Cu-67-2-iminothiolane (2IT)-6-[p-(bromoacetamido)benzyl]-TETA (BAT)-Lym-1 was assessed in this Phase I/II clinical trial for patients wit h non-Hodgkin's lymphoma (NHL) who had failed standard therapy. Up to four doses of Cu-67-2IT-BAT-Lym-1, 25 or 50-60 mCi/m(2)/ dose (0.93 or 1.85-2.22 GBq/m(2)/dose, respectively) were administered; the lower dosage was used when NHL was detected in the bone marrow. Cu-67-2IT-BAT-Lym-1 provided good imaging of NHL, had favorable radiation dosimetry, and had a response rate of 58% (7 of 12). Hematological toxicity was dose-limiting, but no signifi cant nonhematological toxicity was observed. The ability to image and treat NHL patients with a single radiopharmaceutical with useful physical proper ties makes Cu-67-labeled monoclonal antibody an option for future clinical trials, as this study showed that Cu-67-2IT-BAT-Lym-1 was safe, effective, and practical.