A clinical trial of radioimmunotherapy with 67Cu-2IT-BAT-Lym-1 for Non-Hodgkin's lymphoma

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

Research output: Contribution to journalArticle

82 Scopus citations

Abstract

Encouraged by the results of 131I-Lym-1 therapy trials for patients with B-cell non-Hodgkin's lymphoma (NHL), this phase I/II clinical trial of 67Cu-2IT-BAT-Lym-1 was conducted in an effort to further improve the therapeutic index of Lym-1-based radioimmunotherapy. Lym-1 is a mouse monoclonal antibody that preferentially targets malignant lymphocytes. 67Cu has beta emissions comparable to those of 131I but has gamma emissions more favorable for imaging. The macrocyclic chelating agent 1,4,7,11- tetraazacyclotetradecane-N,N',N',N''-tetraacetic acid binds 67Cu tightly to form a stable radioimmunoconjugate in vivo. Methods: All 12 patients had stage III or IV NHL that had not responded to standard therapy; 11 had intermediate- or high-grade NHL. At 4-wk intervals, patients received up to four doses of 67Cu-2IT-BAT-Lym-1, 0.93 or 1.85-2.22 GBq/m2 (25 or 50-60 mCi/m2), with the lower dose used when NHL was detected in the bone marrow. Results: 67Cu-2IT-BAT-Lym-1 provided good imaging of NHL and favorable radiation dosimetry. The mean radiation ratios of tumor to body and tumor to marrow were 28:1 and 15:1, respectively. Tumor-to-lung, -kidney and -liver radiation dose ratios were 7.4:1, 5.3:1 and 2.6:1, respectively. This 67Gu- 2IT-BAT-Lym-1 trial for patients with chemotherapy-resistant NHL had a response rate of 58% (7/12). No significant nonhematologic toxicity was observed. Hematologic toxicity, especially thrombocytopenia, was dose limiting. Conclusion: 67Cu remains an option for future clinical trials. This study established 67Cu-2IT-BAT-Lym-1 as a safe, effective treatment for patients with NHL.

Original languageEnglish (US)
Pages (from-to)2014-2020
Number of pages7
JournalJournal of Nuclear Medicine
Volume40
Issue number12
StatePublished - Dec 1999

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Keywords

  • Cu
  • Antibody
  • Immunotherapy
  • Lymphoma
  • Radiotherapy

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

O'Donnell, R. T., Denardo, G. L., Kukis, D. L., Lamborn, K. R., Shen, S., Yuan, A., Goldstein, D. S., Carr, C. E., Mirick, G. R., & DeNardo, S. J. (1999). A clinical trial of radioimmunotherapy with 67Cu-2IT-BAT-Lym-1 for Non-Hodgkin's lymphoma. Journal of Nuclear Medicine, 40(12), 2014-2020.