67Cu- versus 131I-labeled Lym-1 antibody: Comparative pharmacokinetics and dosimetry in patients with non-Hodgkin's lymphoma

Gerald L Denardo, David L. Kukis, Sui Shen, Diane A. DeNardo, Claude F. Meares, Sally J. DeNardo

Research output: Contribution to journalArticle

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Abstract

Antilymphoma mouse monoclonal antibody (MoAb) Lym-1, labeled with 67Cu or 131I, has demonstrated promising results in radioimmunotherapy (RIT) for lymphoma. Although 131I has played a central role in RIT thus far, some properties of 67Cu are preferable. A subset of our patients received both 67Cu- and 131I-labeled Lym-1, allowing a comparative evaluation of the two radiopharmaceuticals administered to a matched population of patients. Four patients with B-lymphocytic non-Hodgkin's lymphoma that had progressed despite standard therapy entered trials of 67Cu- and 131I- labeled Lym-1, which were injected 3-26 days apart. Lym-1 was conjugated to 6-[p-(bromoacetamido)benzyl]-1,4,7,11-tetraazacyclotetradecane- N,N',N'',N'''-tetraacetic acid (BAT) via 2-iminothiolane (2IT) and radiolabeled with 67Cu to prepare 67Cu-2IT-BAT-Lym-1; 131I-Lym-1 was prepared by the chloramine-T reaction. Planar imaging was used to quantitate 67Cu-2IT-BAT-Lym-1 or 131I-Lym-1 in organs and tumors daily for 3 days or longer. 67Cu-2IT-BAT-Lym-1 exhibited higher peak concentration in 92% (12 of 13) of tumors and a longer biological half-time in every tumor than 131I-Lym-1. The mean tumor concentration (%ID/g) of 67Cu-2IT-BAT-Lym-1 was 1.7, 2.2, and 2.8 times that of 131I-Lym-1 at 0, 24, and 48 h after injection, respectively. The mean biological half-times of 67Cu-2IT-BAT- Lym-1 and 131I-Lym-1 in tumor were 8.8 and 2.3 days, respectively. Consequently, the mean tumor radiation dose delivered by 67Cu-2IT-BAT-Lym- 1 was twice that of 131I-Lym-1, 2.8 (range 0.8-6.7), and 1.4 (range 0.4- 3.5) Gy/GBq, respectively. 67Cu-2IT-BAT-Lym-1 delivered a lower marrow radiation dose than 131I-Lym-1; hence, the tumor:marrow therapeutic indices were 29 and 9.7, respectively. Radiation doses from 67Cu-2IT-BAT- Lym-1 and 131I-Lym-1 to normal tissues were similar except for liver, which received a higher dose from 67Cu-2IT-BAT-Lym-1. Images obtained with 67Cu-2IT-BAT-Lym-1 were superior. Radiation dosimetry data for 67Cu-2IT- BAT-Lym-1 and 131I-Lym-1 agreed with corresponding data from the larger populations of patients from which the matched population for the current study was drawn. In conclusion, 67Cu-2IT-BAT-Lym-1 given to non-Hodgkin's lymphoma patients in close temporal proximity to 131I-Lym-1 exhibited greater uptake and longer retention in tumor, resulting in higher radiation dose and therapeutic index than 131I-Lym-1. These as well as other factors suggest that 67Cu-2IT-BAT-Lym-1 may be superior to 131I-Lym-1 for RIT.

Original languageEnglish (US)
Pages (from-to)533-541
Number of pages9
JournalClinical Cancer Research
Volume5
Issue number3
StatePublished - Mar 1999

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Non-Hodgkin's Lymphoma
Pharmacokinetics
Antibodies
Radioimmunotherapy
Neoplasms
Radiation
methyl 4-mercaptobutyrimidate
Bone Marrow
Population
Radiometry
Radiopharmaceuticals
Lymphoma
Therapeutics

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

67Cu- versus 131I-labeled Lym-1 antibody : Comparative pharmacokinetics and dosimetry in patients with non-Hodgkin's lymphoma. / Denardo, Gerald L; Kukis, David L.; Shen, Sui; DeNardo, Diane A.; Meares, Claude F.; DeNardo, Sally J.

In: Clinical Cancer Research, Vol. 5, No. 3, 03.1999, p. 533-541.

Research output: Contribution to journalArticle

Denardo, Gerald L ; Kukis, David L. ; Shen, Sui ; DeNardo, Diane A. ; Meares, Claude F. ; DeNardo, Sally J. / 67Cu- versus 131I-labeled Lym-1 antibody : Comparative pharmacokinetics and dosimetry in patients with non-Hodgkin's lymphoma. In: Clinical Cancer Research. 1999 ; Vol. 5, No. 3. pp. 533-541.
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abstract = "Antilymphoma mouse monoclonal antibody (MoAb) Lym-1, labeled with 67Cu or 131I, has demonstrated promising results in radioimmunotherapy (RIT) for lymphoma. Although 131I has played a central role in RIT thus far, some properties of 67Cu are preferable. A subset of our patients received both 67Cu- and 131I-labeled Lym-1, allowing a comparative evaluation of the two radiopharmaceuticals administered to a matched population of patients. Four patients with B-lymphocytic non-Hodgkin's lymphoma that had progressed despite standard therapy entered trials of 67Cu- and 131I- labeled Lym-1, which were injected 3-26 days apart. Lym-1 was conjugated to 6-[p-(bromoacetamido)benzyl]-1,4,7,11-tetraazacyclotetradecane- N,N',N'',N'''-tetraacetic acid (BAT) via 2-iminothiolane (2IT) and radiolabeled with 67Cu to prepare 67Cu-2IT-BAT-Lym-1; 131I-Lym-1 was prepared by the chloramine-T reaction. Planar imaging was used to quantitate 67Cu-2IT-BAT-Lym-1 or 131I-Lym-1 in organs and tumors daily for 3 days or longer. 67Cu-2IT-BAT-Lym-1 exhibited higher peak concentration in 92{\%} (12 of 13) of tumors and a longer biological half-time in every tumor than 131I-Lym-1. The mean tumor concentration ({\%}ID/g) of 67Cu-2IT-BAT-Lym-1 was 1.7, 2.2, and 2.8 times that of 131I-Lym-1 at 0, 24, and 48 h after injection, respectively. The mean biological half-times of 67Cu-2IT-BAT- Lym-1 and 131I-Lym-1 in tumor were 8.8 and 2.3 days, respectively. Consequently, the mean tumor radiation dose delivered by 67Cu-2IT-BAT-Lym- 1 was twice that of 131I-Lym-1, 2.8 (range 0.8-6.7), and 1.4 (range 0.4- 3.5) Gy/GBq, respectively. 67Cu-2IT-BAT-Lym-1 delivered a lower marrow radiation dose than 131I-Lym-1; hence, the tumor:marrow therapeutic indices were 29 and 9.7, respectively. Radiation doses from 67Cu-2IT-BAT- Lym-1 and 131I-Lym-1 to normal tissues were similar except for liver, which received a higher dose from 67Cu-2IT-BAT-Lym-1. Images obtained with 67Cu-2IT-BAT-Lym-1 were superior. Radiation dosimetry data for 67Cu-2IT- BAT-Lym-1 and 131I-Lym-1 agreed with corresponding data from the larger populations of patients from which the matched population for the current study was drawn. In conclusion, 67Cu-2IT-BAT-Lym-1 given to non-Hodgkin's lymphoma patients in close temporal proximity to 131I-Lym-1 exhibited greater uptake and longer retention in tumor, resulting in higher radiation dose and therapeutic index than 131I-Lym-1. These as well as other factors suggest that 67Cu-2IT-BAT-Lym-1 may be superior to 131I-Lym-1 for RIT.",
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T1 - 67Cu- versus 131I-labeled Lym-1 antibody

T2 - Comparative pharmacokinetics and dosimetry in patients with non-Hodgkin's lymphoma

AU - Denardo, Gerald L

AU - Kukis, David L.

AU - Shen, Sui

AU - DeNardo, Diane A.

AU - Meares, Claude F.

AU - DeNardo, Sally J.

PY - 1999/3

Y1 - 1999/3

N2 - Antilymphoma mouse monoclonal antibody (MoAb) Lym-1, labeled with 67Cu or 131I, has demonstrated promising results in radioimmunotherapy (RIT) for lymphoma. Although 131I has played a central role in RIT thus far, some properties of 67Cu are preferable. A subset of our patients received both 67Cu- and 131I-labeled Lym-1, allowing a comparative evaluation of the two radiopharmaceuticals administered to a matched population of patients. Four patients with B-lymphocytic non-Hodgkin's lymphoma that had progressed despite standard therapy entered trials of 67Cu- and 131I- labeled Lym-1, which were injected 3-26 days apart. Lym-1 was conjugated to 6-[p-(bromoacetamido)benzyl]-1,4,7,11-tetraazacyclotetradecane- N,N',N'',N'''-tetraacetic acid (BAT) via 2-iminothiolane (2IT) and radiolabeled with 67Cu to prepare 67Cu-2IT-BAT-Lym-1; 131I-Lym-1 was prepared by the chloramine-T reaction. Planar imaging was used to quantitate 67Cu-2IT-BAT-Lym-1 or 131I-Lym-1 in organs and tumors daily for 3 days or longer. 67Cu-2IT-BAT-Lym-1 exhibited higher peak concentration in 92% (12 of 13) of tumors and a longer biological half-time in every tumor than 131I-Lym-1. The mean tumor concentration (%ID/g) of 67Cu-2IT-BAT-Lym-1 was 1.7, 2.2, and 2.8 times that of 131I-Lym-1 at 0, 24, and 48 h after injection, respectively. The mean biological half-times of 67Cu-2IT-BAT- Lym-1 and 131I-Lym-1 in tumor were 8.8 and 2.3 days, respectively. Consequently, the mean tumor radiation dose delivered by 67Cu-2IT-BAT-Lym- 1 was twice that of 131I-Lym-1, 2.8 (range 0.8-6.7), and 1.4 (range 0.4- 3.5) Gy/GBq, respectively. 67Cu-2IT-BAT-Lym-1 delivered a lower marrow radiation dose than 131I-Lym-1; hence, the tumor:marrow therapeutic indices were 29 and 9.7, respectively. Radiation doses from 67Cu-2IT-BAT- Lym-1 and 131I-Lym-1 to normal tissues were similar except for liver, which received a higher dose from 67Cu-2IT-BAT-Lym-1. Images obtained with 67Cu-2IT-BAT-Lym-1 were superior. Radiation dosimetry data for 67Cu-2IT- BAT-Lym-1 and 131I-Lym-1 agreed with corresponding data from the larger populations of patients from which the matched population for the current study was drawn. In conclusion, 67Cu-2IT-BAT-Lym-1 given to non-Hodgkin's lymphoma patients in close temporal proximity to 131I-Lym-1 exhibited greater uptake and longer retention in tumor, resulting in higher radiation dose and therapeutic index than 131I-Lym-1. These as well as other factors suggest that 67Cu-2IT-BAT-Lym-1 may be superior to 131I-Lym-1 for RIT.

AB - Antilymphoma mouse monoclonal antibody (MoAb) Lym-1, labeled with 67Cu or 131I, has demonstrated promising results in radioimmunotherapy (RIT) for lymphoma. Although 131I has played a central role in RIT thus far, some properties of 67Cu are preferable. A subset of our patients received both 67Cu- and 131I-labeled Lym-1, allowing a comparative evaluation of the two radiopharmaceuticals administered to a matched population of patients. Four patients with B-lymphocytic non-Hodgkin's lymphoma that had progressed despite standard therapy entered trials of 67Cu- and 131I- labeled Lym-1, which were injected 3-26 days apart. Lym-1 was conjugated to 6-[p-(bromoacetamido)benzyl]-1,4,7,11-tetraazacyclotetradecane- N,N',N'',N'''-tetraacetic acid (BAT) via 2-iminothiolane (2IT) and radiolabeled with 67Cu to prepare 67Cu-2IT-BAT-Lym-1; 131I-Lym-1 was prepared by the chloramine-T reaction. Planar imaging was used to quantitate 67Cu-2IT-BAT-Lym-1 or 131I-Lym-1 in organs and tumors daily for 3 days or longer. 67Cu-2IT-BAT-Lym-1 exhibited higher peak concentration in 92% (12 of 13) of tumors and a longer biological half-time in every tumor than 131I-Lym-1. The mean tumor concentration (%ID/g) of 67Cu-2IT-BAT-Lym-1 was 1.7, 2.2, and 2.8 times that of 131I-Lym-1 at 0, 24, and 48 h after injection, respectively. The mean biological half-times of 67Cu-2IT-BAT- Lym-1 and 131I-Lym-1 in tumor were 8.8 and 2.3 days, respectively. Consequently, the mean tumor radiation dose delivered by 67Cu-2IT-BAT-Lym- 1 was twice that of 131I-Lym-1, 2.8 (range 0.8-6.7), and 1.4 (range 0.4- 3.5) Gy/GBq, respectively. 67Cu-2IT-BAT-Lym-1 delivered a lower marrow radiation dose than 131I-Lym-1; hence, the tumor:marrow therapeutic indices were 29 and 9.7, respectively. Radiation doses from 67Cu-2IT-BAT- Lym-1 and 131I-Lym-1 to normal tissues were similar except for liver, which received a higher dose from 67Cu-2IT-BAT-Lym-1. Images obtained with 67Cu-2IT-BAT-Lym-1 were superior. Radiation dosimetry data for 67Cu-2IT- BAT-Lym-1 and 131I-Lym-1 agreed with corresponding data from the larger populations of patients from which the matched population for the current study was drawn. In conclusion, 67Cu-2IT-BAT-Lym-1 given to non-Hodgkin's lymphoma patients in close temporal proximity to 131I-Lym-1 exhibited greater uptake and longer retention in tumor, resulting in higher radiation dose and therapeutic index than 131I-Lym-1. These as well as other factors suggest that 67Cu-2IT-BAT-Lym-1 may be superior to 131I-Lym-1 for RIT.

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