Antibody responses to macrocycles in lymphoma

G. L. DeNardo, G. R. Mirick, L. A. Kroger, R. T. O'Donnell, C. F. Meares, S. J. DeNardo

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Metallic radioimmunoconjugates have promise for radioimmunoimaging and therapy. Macrocyclic chelating agents allow formation of stable metallic radioimmunoconjugates but have been reported to be immunogenic. This study assesses human antibody responses in patients that were imaged or treated with radiolabeled Lym-1 containing the macrocyclic chelators 1,4,8,11- tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid (TETA) or 1,4,7,10- tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA). Methods: One to six doses (median 1) and 6 to 285 mg (median 33) 67Cu-2lT-BAT (2- iminothiolane bromoacetamidobenzyl TETA)- or 111In-2lT-BAD (2- iminothiolane bromoacetamidobenzyl DOTA)-Lym-1 were administered to each of 18 patients with lymphocytic malignancies. Solid-phase ELISA, utilizing unchelated Lym-1 or human serum albumin conjugated to DOTA, TETA or 2lT- bromoacetamidobenzyl-ethylenediaminetetraacetic acid (BABE) as coating antigens, was used to characterize antibody responses against 67Cu-2lT- BAT-Lym-1 and 111In-2lT-BAD-Lym-1 by quantitating antibodies against the Lym-1, DOTA, TETA or 2lT moieties, respectively. Results: None of the patients had evidence for serum sickness. No patient that received 111In- 21T-BAD-Lym-1 developed antibodies to Lym-1 or DOTA. Two (15%) of the 13 patients that received 67Cu-2lT-BAT-Lym-1 developed antibodies against both TETA and Lym-1, and an additional patient developed antibodies against Lym-1 only. No patient developed an antibody response solely against the macrocycle, nor did any of the patients generate antibodies against the 2lT molecule. HAMA levels were many times greater in amount than HATA levels even when their relative molecular masses were considered. Conclusion: Although macrocycles such as DOTA and TETA, and other chelates, can be haptens and thus potentially immunogenic, our findings do not support the view that macrocycles are more immunogenic than other radiometal chelating agents.

Original languageEnglish (US)
Pages (from-to)451-456
Number of pages6
JournalJournal of Nuclear Medicine
Volume37
Issue number3
StatePublished - Mar 1996

Fingerprint

Antibody Formation
Lymphoma
Chelating Agents
Antibodies
Immunoconjugates
Acids
Radioimmunodetection
Serum Sickness
Haptens
Serum Albumin
Edetic Acid
Enzyme-Linked Immunosorbent Assay
Antigens
1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid
Neoplasms

Keywords

  • anti-macro-cycle antibodies
  • HAMA
  • lymphoma
  • radioimmunotherapy

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

DeNardo, G. L., Mirick, G. R., Kroger, L. A., O'Donnell, R. T., Meares, C. F., & DeNardo, S. J. (1996). Antibody responses to macrocycles in lymphoma. Journal of Nuclear Medicine, 37(3), 451-456.

Antibody responses to macrocycles in lymphoma. / DeNardo, G. L.; Mirick, G. R.; Kroger, L. A.; O'Donnell, R. T.; Meares, C. F.; DeNardo, S. J.

In: Journal of Nuclear Medicine, Vol. 37, No. 3, 03.1996, p. 451-456.

Research output: Contribution to journalArticle

DeNardo, GL, Mirick, GR, Kroger, LA, O'Donnell, RT, Meares, CF & DeNardo, SJ 1996, 'Antibody responses to macrocycles in lymphoma', Journal of Nuclear Medicine, vol. 37, no. 3, pp. 451-456.
DeNardo GL, Mirick GR, Kroger LA, O'Donnell RT, Meares CF, DeNardo SJ. Antibody responses to macrocycles in lymphoma. Journal of Nuclear Medicine. 1996 Mar;37(3):451-456.
DeNardo, G. L. ; Mirick, G. R. ; Kroger, L. A. ; O'Donnell, R. T. ; Meares, C. F. ; DeNardo, S. J. / Antibody responses to macrocycles in lymphoma. In: Journal of Nuclear Medicine. 1996 ; Vol. 37, No. 3. pp. 451-456.
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abstract = "Metallic radioimmunoconjugates have promise for radioimmunoimaging and therapy. Macrocyclic chelating agents allow formation of stable metallic radioimmunoconjugates but have been reported to be immunogenic. This study assesses human antibody responses in patients that were imaged or treated with radiolabeled Lym-1 containing the macrocyclic chelators 1,4,8,11- tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid (TETA) or 1,4,7,10- tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA). Methods: One to six doses (median 1) and 6 to 285 mg (median 33) 67Cu-2lT-BAT (2- iminothiolane bromoacetamidobenzyl TETA)- or 111In-2lT-BAD (2- iminothiolane bromoacetamidobenzyl DOTA)-Lym-1 were administered to each of 18 patients with lymphocytic malignancies. Solid-phase ELISA, utilizing unchelated Lym-1 or human serum albumin conjugated to DOTA, TETA or 2lT- bromoacetamidobenzyl-ethylenediaminetetraacetic acid (BABE) as coating antigens, was used to characterize antibody responses against 67Cu-2lT- BAT-Lym-1 and 111In-2lT-BAD-Lym-1 by quantitating antibodies against the Lym-1, DOTA, TETA or 2lT moieties, respectively. Results: None of the patients had evidence for serum sickness. No patient that received 111In- 21T-BAD-Lym-1 developed antibodies to Lym-1 or DOTA. Two (15{\%}) of the 13 patients that received 67Cu-2lT-BAT-Lym-1 developed antibodies against both TETA and Lym-1, and an additional patient developed antibodies against Lym-1 only. No patient developed an antibody response solely against the macrocycle, nor did any of the patients generate antibodies against the 2lT molecule. HAMA levels were many times greater in amount than HATA levels even when their relative molecular masses were considered. Conclusion: Although macrocycles such as DOTA and TETA, and other chelates, can be haptens and thus potentially immunogenic, our findings do not support the view that macrocycles are more immunogenic than other radiometal chelating agents.",
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AU - DeNardo, G. L.

AU - Mirick, G. R.

AU - Kroger, L. A.

AU - O'Donnell, R. T.

AU - Meares, C. F.

AU - DeNardo, S. J.

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N2 - Metallic radioimmunoconjugates have promise for radioimmunoimaging and therapy. Macrocyclic chelating agents allow formation of stable metallic radioimmunoconjugates but have been reported to be immunogenic. This study assesses human antibody responses in patients that were imaged or treated with radiolabeled Lym-1 containing the macrocyclic chelators 1,4,8,11- tetraazacyclotetradecane-N,N',N'',N'''-tetraacetic acid (TETA) or 1,4,7,10- tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA). Methods: One to six doses (median 1) and 6 to 285 mg (median 33) 67Cu-2lT-BAT (2- iminothiolane bromoacetamidobenzyl TETA)- or 111In-2lT-BAD (2- iminothiolane bromoacetamidobenzyl DOTA)-Lym-1 were administered to each of 18 patients with lymphocytic malignancies. Solid-phase ELISA, utilizing unchelated Lym-1 or human serum albumin conjugated to DOTA, TETA or 2lT- bromoacetamidobenzyl-ethylenediaminetetraacetic acid (BABE) as coating antigens, was used to characterize antibody responses against 67Cu-2lT- BAT-Lym-1 and 111In-2lT-BAD-Lym-1 by quantitating antibodies against the Lym-1, DOTA, TETA or 2lT moieties, respectively. Results: None of the patients had evidence for serum sickness. No patient that received 111In- 21T-BAD-Lym-1 developed antibodies to Lym-1 or DOTA. Two (15%) of the 13 patients that received 67Cu-2lT-BAT-Lym-1 developed antibodies against both TETA and Lym-1, and an additional patient developed antibodies against Lym-1 only. No patient developed an antibody response solely against the macrocycle, nor did any of the patients generate antibodies against the 2lT molecule. HAMA levels were many times greater in amount than HATA levels even when their relative molecular masses were considered. Conclusion: Although macrocycles such as DOTA and TETA, and other chelates, can be haptens and thus potentially immunogenic, our findings do not support the view that macrocycles are more immunogenic than other radiometal chelating agents.

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