Relative therapeutic efficacy of 125I- and 131I-labeled monoclonal antibody A33 in a human colon cancer xenograft

E. C. Barendswaard, J. L. Humm, J. A. O'Donoghue, George Sgouros, R. D. Finn, A. M. Scott, S. M. Larson, S. Welt

Research output: Contribution to journalArticle

Abstract

A33, a monoclonal antibody that targets colon carcinomas, was labeled with 125I or 131I and the relative therapeutic efficacy of the 2 radiolabeled species was compared in a human colon cancer xenograft system. Methods: Nude mice bearing human SW1222 colon carcinoma xenografts were administered escalating activities of 125I-A33 (9.25-148 MBq) or 131I-A33 (0.925-18.5 MBq), 125I- and 131I-labeled control antibodies, unlabeled antibody, or no antibody. The effects of treatment were assessed using the endpoints of tumor growth delay and cure. Results: Tumor growth delay increased with administered activity for all radiolabeled antibodies. Approximately 4.5 times more activity was required for 125I-A33 to produce therapeutic effects that were equivalent to those of 131I-A33. This ratio was approximately 7 for a nonspecific, noninternalizing isotype-matched, radiolabeled control antibody. Unlabeled A33 antibody had no effect on tumor growth. Approximately 10 times more activity of 125I-A33 produced toxicity similar to that of 131I-A33, and this ratio fell to approximately 6 for radiolabeled control antibody. Conclusion: Treatment with 125I-A33 resulted in a relative therapeutic gain of approximately 2 compared with 131I-A33 in this experimental system.

Original languageEnglish (US)
Pages (from-to)1251-1256
Number of pages6
JournalJournal of Nuclear Medicine
Volume42
Issue number8
StatePublished - 2001
Externally publishedYes

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losigame
Heterografts
Colonic Neoplasms
Monoclonal Antibodies
Antibodies
Therapeutics
Colon
Growth
Carcinoma
Neoplasms
Therapeutic Uses
Nude Mice

Keywords

  • Colon cancer xenograft
  • Radiolabeled mAb A33
  • Targeting
  • Therapeutic efficacy

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Barendswaard, E. C., Humm, J. L., O'Donoghue, J. A., Sgouros, G., Finn, R. D., Scott, A. M., ... Welt, S. (2001). Relative therapeutic efficacy of 125I- and 131I-labeled monoclonal antibody A33 in a human colon cancer xenograft. Journal of Nuclear Medicine, 42(8), 1251-1256.

Relative therapeutic efficacy of 125I- and 131I-labeled monoclonal antibody A33 in a human colon cancer xenograft. / Barendswaard, E. C.; Humm, J. L.; O'Donoghue, J. A.; Sgouros, George; Finn, R. D.; Scott, A. M.; Larson, S. M.; Welt, S.

In: Journal of Nuclear Medicine, Vol. 42, No. 8, 2001, p. 1251-1256.

Research output: Contribution to journalArticle

Barendswaard, EC, Humm, JL, O'Donoghue, JA, Sgouros, G, Finn, RD, Scott, AM, Larson, SM & Welt, S 2001, 'Relative therapeutic efficacy of 125I- and 131I-labeled monoclonal antibody A33 in a human colon cancer xenograft', Journal of Nuclear Medicine, vol. 42, no. 8, pp. 1251-1256.
Barendswaard, E. C. ; Humm, J. L. ; O'Donoghue, J. A. ; Sgouros, George ; Finn, R. D. ; Scott, A. M. ; Larson, S. M. ; Welt, S. / Relative therapeutic efficacy of 125I- and 131I-labeled monoclonal antibody A33 in a human colon cancer xenograft. In: Journal of Nuclear Medicine. 2001 ; Vol. 42, No. 8. pp. 1251-1256.
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abstract = "A33, a monoclonal antibody that targets colon carcinomas, was labeled with 125I or 131I and the relative therapeutic efficacy of the 2 radiolabeled species was compared in a human colon cancer xenograft system. Methods: Nude mice bearing human SW1222 colon carcinoma xenografts were administered escalating activities of 125I-A33 (9.25-148 MBq) or 131I-A33 (0.925-18.5 MBq), 125I- and 131I-labeled control antibodies, unlabeled antibody, or no antibody. The effects of treatment were assessed using the endpoints of tumor growth delay and cure. Results: Tumor growth delay increased with administered activity for all radiolabeled antibodies. Approximately 4.5 times more activity was required for 125I-A33 to produce therapeutic effects that were equivalent to those of 131I-A33. This ratio was approximately 7 for a nonspecific, noninternalizing isotype-matched, radiolabeled control antibody. Unlabeled A33 antibody had no effect on tumor growth. Approximately 10 times more activity of 125I-A33 produced toxicity similar to that of 131I-A33, and this ratio fell to approximately 6 for radiolabeled control antibody. Conclusion: Treatment with 125I-A33 resulted in a relative therapeutic gain of approximately 2 compared with 131I-A33 in this experimental system.",
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T1 - Relative therapeutic efficacy of 125I- and 131I-labeled monoclonal antibody A33 in a human colon cancer xenograft

AU - Barendswaard, E. C.

AU - Humm, J. L.

AU - O'Donoghue, J. A.

AU - Sgouros, George

AU - Finn, R. D.

AU - Scott, A. M.

AU - Larson, S. M.

AU - Welt, S.

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N2 - A33, a monoclonal antibody that targets colon carcinomas, was labeled with 125I or 131I and the relative therapeutic efficacy of the 2 radiolabeled species was compared in a human colon cancer xenograft system. Methods: Nude mice bearing human SW1222 colon carcinoma xenografts were administered escalating activities of 125I-A33 (9.25-148 MBq) or 131I-A33 (0.925-18.5 MBq), 125I- and 131I-labeled control antibodies, unlabeled antibody, or no antibody. The effects of treatment were assessed using the endpoints of tumor growth delay and cure. Results: Tumor growth delay increased with administered activity for all radiolabeled antibodies. Approximately 4.5 times more activity was required for 125I-A33 to produce therapeutic effects that were equivalent to those of 131I-A33. This ratio was approximately 7 for a nonspecific, noninternalizing isotype-matched, radiolabeled control antibody. Unlabeled A33 antibody had no effect on tumor growth. Approximately 10 times more activity of 125I-A33 produced toxicity similar to that of 131I-A33, and this ratio fell to approximately 6 for radiolabeled control antibody. Conclusion: Treatment with 125I-A33 resulted in a relative therapeutic gain of approximately 2 compared with 131I-A33 in this experimental system.

AB - A33, a monoclonal antibody that targets colon carcinomas, was labeled with 125I or 131I and the relative therapeutic efficacy of the 2 radiolabeled species was compared in a human colon cancer xenograft system. Methods: Nude mice bearing human SW1222 colon carcinoma xenografts were administered escalating activities of 125I-A33 (9.25-148 MBq) or 131I-A33 (0.925-18.5 MBq), 125I- and 131I-labeled control antibodies, unlabeled antibody, or no antibody. The effects of treatment were assessed using the endpoints of tumor growth delay and cure. Results: Tumor growth delay increased with administered activity for all radiolabeled antibodies. Approximately 4.5 times more activity was required for 125I-A33 to produce therapeutic effects that were equivalent to those of 131I-A33. This ratio was approximately 7 for a nonspecific, noninternalizing isotype-matched, radiolabeled control antibody. Unlabeled A33 antibody had no effect on tumor growth. Approximately 10 times more activity of 125I-A33 produced toxicity similar to that of 131I-A33, and this ratio fell to approximately 6 for radiolabeled control antibody. Conclusion: Treatment with 125I-A33 resulted in a relative therapeutic gain of approximately 2 compared with 131I-A33 in this experimental system.

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