Effect of mass of 111In-benzyl-EDTA monoclonal antibody on hepatic uptake and processing in mice

G. P. Adams, S. J. DeNardo, S. V. Deshpande, Gerald L Denardo, C. F. Meares, M. J. McCall, A. L. Epstein

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

In patients, the pharmacokinetic behavior of murine monoclonal antibodies has been observed to vary with the amount of antibody administered. It has been suggested that this reflects human recognition of the foreign mouse protein. We have found that the amount of antibody administered also influenced pharmacokinetic behavior when murine monoclonal antibody was administered to mice. p-Isothiocyanatobenzyl-EDTA, a new chelator which forms complexes with 111In that are stable in vivo, was conjugated to Lym-1, a murine anti-Burkitt's lymphoma monoclonal antibody. The pharmacokinetics of two doses (20 and 0.2 μg) of the 111In labeled radiopharmaceutical were studied in non-tumor bearing BALB/c mice. About 20% (0.04 μg) of the 0.2-μg dose, compared with 8% (1.6 μg) of the 20-μg dose, was found in the liver at 48 h after injection. Both doses demonstrated a biological half-life of approximately 120 h. At least 75% of the 111In was excreted by the kidneys, and essentially all 111In in the urine remained chelated by the EDTA portion of p-isothiocyanatobenzyl-EDTA. From these observations of a dose dependent uptake of this radiopharmaceutical by the liver we conclude that there is a recognition phenomenon in mice for this murine monoclonal antibody.

Original languageEnglish (US)
Pages (from-to)1707-1711
Number of pages5
JournalCancer Research
Volume49
Issue number7
StatePublished - 1989

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Monoclonal Antibodies
Radiopharmaceuticals
Pharmacokinetics
Liver
Burkitt Lymphoma
Antibodies
Chelating Agents
Edetic Acid
Half-Life
Urine
Kidney
Injections
benzyl-EDTA
Proteins
isothiocyanatobenzyl-EDTA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Adams, G. P., DeNardo, S. J., Deshpande, S. V., Denardo, G. L., Meares, C. F., McCall, M. J., & Epstein, A. L. (1989). Effect of mass of 111In-benzyl-EDTA monoclonal antibody on hepatic uptake and processing in mice. Cancer Research, 49(7), 1707-1711.

Effect of mass of 111In-benzyl-EDTA monoclonal antibody on hepatic uptake and processing in mice. / Adams, G. P.; DeNardo, S. J.; Deshpande, S. V.; Denardo, Gerald L; Meares, C. F.; McCall, M. J.; Epstein, A. L.

In: Cancer Research, Vol. 49, No. 7, 1989, p. 1707-1711.

Research output: Contribution to journalArticle

Adams, GP, DeNardo, SJ, Deshpande, SV, Denardo, GL, Meares, CF, McCall, MJ & Epstein, AL 1989, 'Effect of mass of 111In-benzyl-EDTA monoclonal antibody on hepatic uptake and processing in mice', Cancer Research, vol. 49, no. 7, pp. 1707-1711.
Adams GP, DeNardo SJ, Deshpande SV, Denardo GL, Meares CF, McCall MJ et al. Effect of mass of 111In-benzyl-EDTA monoclonal antibody on hepatic uptake and processing in mice. Cancer Research. 1989;49(7):1707-1711.
Adams, G. P. ; DeNardo, S. J. ; Deshpande, S. V. ; Denardo, Gerald L ; Meares, C. F. ; McCall, M. J. ; Epstein, A. L. / Effect of mass of 111In-benzyl-EDTA monoclonal antibody on hepatic uptake and processing in mice. In: Cancer Research. 1989 ; Vol. 49, No. 7. pp. 1707-1711.
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AB - In patients, the pharmacokinetic behavior of murine monoclonal antibodies has been observed to vary with the amount of antibody administered. It has been suggested that this reflects human recognition of the foreign mouse protein. We have found that the amount of antibody administered also influenced pharmacokinetic behavior when murine monoclonal antibody was administered to mice. p-Isothiocyanatobenzyl-EDTA, a new chelator which forms complexes with 111In that are stable in vivo, was conjugated to Lym-1, a murine anti-Burkitt's lymphoma monoclonal antibody. The pharmacokinetics of two doses (20 and 0.2 μg) of the 111In labeled radiopharmaceutical were studied in non-tumor bearing BALB/c mice. About 20% (0.04 μg) of the 0.2-μg dose, compared with 8% (1.6 μg) of the 20-μg dose, was found in the liver at 48 h after injection. Both doses demonstrated a biological half-life of approximately 120 h. At least 75% of the 111In was excreted by the kidneys, and essentially all 111In in the urine remained chelated by the EDTA portion of p-isothiocyanatobenzyl-EDTA. From these observations of a dose dependent uptake of this radiopharmaceutical by the liver we conclude that there is a recognition phenomenon in mice for this murine monoclonal antibody.

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