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

Copper-67 (⁶⁷Cu) has ideal properties for radioimmunotherapy. The 62-h half-life is similar to the residence time of antibodies in tumor, and the therapeutic β emission of ⁶⁷Cu is comparable to that of ¹³¹I. ⁶⁷Cu, however, has γ emissions similar to ^99mtechnetium that are favorable for imaging. The macrocyclic chelating agent 1,4,7,11-tetraazacyclotetradecane- N,N',N'',N'''-tetraacetic acid (TETA) binds ⁶⁷Cu tightly and selectively, facilitating linkage to Lym-1, a mouse monoclonal antibody that preferentially targets malignant lymphocytes. The safety, efficacy, and practicality of ⁶⁷Cu-2-iminothiolane (2IT)-6-[p-(bromoacetamido)benzyl]- TETA (BAT)-Lym-1 was assessed in this Phase I/II clinical trial for patients with non-Hodgkin's lymphoma (NHL) who had failed standard therapy. Up to four doses of ⁶⁷Cu-2IT-BAT-Lym-1, 25 or 50-60 mCi/m²/dose (0.93 or 1.85-2.22 GBq/m²/dose, respectively) were administered; the lower dosage was used when NHL was detected in the bone marrow. ⁶⁷Cu-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 significant nonhematological toxicity was observed. The ability to image and treat NHL patients with a single radiopharmaceutical with useful physical properties makes ⁶⁷Cu-labeled monoclonal antibody an option for future clinical trials, as this study showed that ⁶⁷Cu-2IT-BAT-Lym-1 was safe, effective, and practical.