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

81 Citations (Scopus)

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

Fingerprint

Radioimmunotherapy
Non-Hodgkin's Lymphoma
Clinical Trials
Bone Marrow
Immunoconjugates
Radiation
Radiometry
Neoplasms
Phase II Clinical Trials
Clinical Trials, Phase I
copper-67-2IT-BAT-Lym-1
B-Cell Lymphoma
Therapeutics
Chelating Agents
Thrombocytopenia
Monoclonal Antibodies
Lymphocytes
Kidney
Drug Therapy
Lung

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., ... 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.

A clinical trial of radioimmunotherapy with 67Cu-2IT-BAT-Lym-1 for Non-Hodgkin's lymphoma. / O'Donnell, Robert T; Denardo, Gerald L; Kukis, David L.; Lamborn, Kathleen R.; Shen, Sui; Yuan, Aina; Goldstein, Desiree S.; Carr, Catherine E.; Mirick, Gary R.; DeNardo, Sally J.

In: Journal of Nuclear Medicine, Vol. 40, No. 12, 12.1999, p. 2014-2020.

Research output: Contribution to journalArticle

O'Donnell, RT, Denardo, GL, Kukis, DL, Lamborn, KR, Shen, S, Yuan, A, Goldstein, DS, Carr, CE, Mirick, GR & DeNardo, SJ 1999, 'A clinical trial of radioimmunotherapy with 67Cu-2IT-BAT-Lym-1 for Non-Hodgkin's lymphoma', Journal of Nuclear Medicine, vol. 40, no. 12, pp. 2014-2020.
O'Donnell, Robert T ; Denardo, Gerald L ; Kukis, David L. ; Lamborn, Kathleen R. ; Shen, Sui ; Yuan, Aina ; Goldstein, Desiree S. ; Carr, Catherine E. ; Mirick, Gary R. ; DeNardo, Sally J. / A clinical trial of radioimmunotherapy with 67Cu-2IT-BAT-Lym-1 for Non-Hodgkin's lymphoma. In: Journal of Nuclear Medicine. 1999 ; Vol. 40, No. 12. pp. 2014-2020.
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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.",
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AU - Shen, Sui

AU - Yuan, Aina

AU - Goldstein, Desiree S.

AU - Carr, Catherine E.

AU - Mirick, Gary R.

AU - DeNardo, Sally J.

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