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

Research output: Contribution to journalArticle

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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

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Radioimmunotherapy
Non-Hodgkin's Lymphoma
Acids
Monoclonal Antibodies
Radiometry
Neoplasm Antibodies
Phase II Clinical Trials
Clinical Trials, Phase I
Radiopharmaceuticals
Chelating Agents
Half-Life
Copper
Bone Marrow
Clinical Trials
Lymphocytes
Safety
methyl 4-mercaptobutyrimidate
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

67Copper-2-iminothiolane-6-[p-(bromoacetamido)benzyl]-TETA-Lym-1 for radioimmunotherapy of non-Hodgkin's lymphoma. / O'Donnell, Robert T; Denardo, Gerald L; Kukis, David L.; Lamborn, Kathleen R.; Shen, Sui; Yuan, Aina; Goldstein, Desiree S.; Mirick, Gary R.; DeNardo, Sally J.

In: Clinical Cancer Research, Vol. 5, No. 10 SUPPL., 10.1999.

Research output: Contribution to journalArticle

O'Donnell, RT, Denardo, GL, Kukis, DL, Lamborn, KR, Shen, S, Yuan, A, Goldstein, DS, Mirick, GR & DeNardo, SJ 1999, '67Copper-2-iminothiolane-6-[p-(bromoacetamido)benzyl]-TETA-Lym-1 for radioimmunotherapy of non-Hodgkin's lymphoma', Clinical Cancer Research, vol. 5, no. 10 SUPPL..
O'Donnell, Robert T ; Denardo, Gerald L ; Kukis, David L. ; Lamborn, Kathleen R. ; Shen, Sui ; Yuan, Aina ; Goldstein, Desiree S. ; Mirick, Gary R. ; DeNardo, Sally J. / 67Copper-2-iminothiolane-6-[p-(bromoacetamido)benzyl]-TETA-Lym-1 for radioimmunotherapy of non-Hodgkin's lymphoma. In: Clinical Cancer Research. 1999 ; Vol. 5, No. 10 SUPPL.
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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.",
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AU - O'Donnell, Robert T

AU - Denardo, Gerald L

AU - Kukis, David L.

AU - Lamborn, Kathleen R.

AU - Shen, Sui

AU - Yuan, Aina

AU - Goldstein, Desiree S.

AU - Mirick, Gary R.

AU - DeNardo, Sally J.

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