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

Robert T O'Donnell, Gerald L Denardo, David L. Kukis, Kathleen R. Lamborn, Sui Shen, Aina Yuan, Desiree S. Goldstein, Gary R. Mirick, Sally J. DeNardo

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46 Scopus citations

Abstract

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.

Original languageEnglish (US)
JournalClinical Cancer Research
Volume5
Issue number10 SUPPL.
StatePublished - Oct 1999

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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    O'Donnell, R. T., Denardo, G. L., Kukis, D. L., Lamborn, K. R., Shen, S., Yuan, A., Goldstein, D. S., Mirick, G. R., & DeNardo, S. J. (1999). 67Copper-2-iminothiolane-6-[p-(bromoacetamido)benzyl]-TETA-Lym-1 for radioimmunotherapy of non-Hodgkin's lymphoma. Clinical Cancer Research, 5(10 SUPPL.).