Radioimaging and pharmacokinetics of 111Indium-labeled ZME 018 monoclonal antibody (MOAB) in malignant melanoma

J. L. Murray, M. Rosenblum, L. Lamki

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Abstract

An 111Indium (111In)-labeled MoAb ZME 018 which reacts with a 240 Kd melanoma-associated antigen was administered to 12 patients with metastatic melanoma. MoAb was coupled to 5 mCi 111In and infused over 2 h at doses of 2.5 mg (5 pts). 5 mg (5 pts), and 10 mg (2 pts). Total body tomograms and region of interest scans were performed at 2, 24 and 72 hours post infusion. No adverse side effects were noted. There was rapid blood pool distribution to spleen, bone, bone marrow, liver, and testes. Tumor sites could be visualized as early as 24 hours but were more easily seen at 72 hours due to less background radioactivity. Seventeen of 41 (41%) previously documented metastases imaged. More sites imaged with increasing concentrations of MoAb, i.e., 25% @ 2.5 mg; 67% @ 5 mg; 75% @ 10 mg. In two instances, uptake of 111In occurred in previously undiagnosed sites. The pharmacokinetics of MoAb were analyzed at each dose level. At the 5 mg dose, the terminal phase half-life for111In in plasma was 24.5 ± 2.7 hours. The apparent volume of distribution (Vd) wa 4.03 ± .5l similar to the plasma value, and the calculated clearance rate for 111In label was 0.259 ± 0.002 ml/kg/min. Mean urinary excretion of 111In label was 8.7 ± 0.6% of the administered dose over 48 hours after administration. The calculated pharmacokinetic parameters were independent of antibody dose. In contrast to previous studies with other anti-melanoma MoAb, ZME 018 was cleared more rapidly from plasma. Tumor localization occurred in a significant number of patients especially at MoAb doses above 2.5 mg.

Original languageEnglish
JournalProceedings of the American Association for Cancer Research
VolumeVOL. 26
Publication statusPublished - 1985

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Melanoma
Pharmacokinetics
Monoclonal Antibodies
Melanoma-Specific Antigens
Body Regions
Radioactivity
Half-Life
Testis
Neoplasms
Spleen
Bone Marrow
Neoplasm Metastasis
Bone and Bones
Antibodies
Liver

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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title = "Radioimaging and pharmacokinetics of 111Indium-labeled ZME 018 monoclonal antibody (MOAB) in malignant melanoma",
abstract = "An 111Indium (111In)-labeled MoAb ZME 018 which reacts with a 240 Kd melanoma-associated antigen was administered to 12 patients with metastatic melanoma. MoAb was coupled to 5 mCi 111In and infused over 2 h at doses of 2.5 mg (5 pts). 5 mg (5 pts), and 10 mg (2 pts). Total body tomograms and region of interest scans were performed at 2, 24 and 72 hours post infusion. No adverse side effects were noted. There was rapid blood pool distribution to spleen, bone, bone marrow, liver, and testes. Tumor sites could be visualized as early as 24 hours but were more easily seen at 72 hours due to less background radioactivity. Seventeen of 41 (41{\%}) previously documented metastases imaged. More sites imaged with increasing concentrations of MoAb, i.e., 25{\%} @ 2.5 mg; 67{\%} @ 5 mg; 75{\%} @ 10 mg. In two instances, uptake of 111In occurred in previously undiagnosed sites. The pharmacokinetics of MoAb were analyzed at each dose level. At the 5 mg dose, the terminal phase half-life for111In in plasma was 24.5 ± 2.7 hours. The apparent volume of distribution (Vd) wa 4.03 ± .5l similar to the plasma value, and the calculated clearance rate for 111In label was 0.259 ± 0.002 ml/kg/min. Mean urinary excretion of 111In label was 8.7 ± 0.6{\%} of the administered dose over 48 hours after administration. The calculated pharmacokinetic parameters were independent of antibody dose. In contrast to previous studies with other anti-melanoma MoAb, ZME 018 was cleared more rapidly from plasma. Tumor localization occurred in a significant number of patients especially at MoAb doses above 2.5 mg.",
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T1 - Radioimaging and pharmacokinetics of 111Indium-labeled ZME 018 monoclonal antibody (MOAB) in malignant melanoma

AU - Murray, J. L.

AU - Rosenblum, M.

AU - Lamki, L.

PY - 1985

Y1 - 1985

N2 - An 111Indium (111In)-labeled MoAb ZME 018 which reacts with a 240 Kd melanoma-associated antigen was administered to 12 patients with metastatic melanoma. MoAb was coupled to 5 mCi 111In and infused over 2 h at doses of 2.5 mg (5 pts). 5 mg (5 pts), and 10 mg (2 pts). Total body tomograms and region of interest scans were performed at 2, 24 and 72 hours post infusion. No adverse side effects were noted. There was rapid blood pool distribution to spleen, bone, bone marrow, liver, and testes. Tumor sites could be visualized as early as 24 hours but were more easily seen at 72 hours due to less background radioactivity. Seventeen of 41 (41%) previously documented metastases imaged. More sites imaged with increasing concentrations of MoAb, i.e., 25% @ 2.5 mg; 67% @ 5 mg; 75% @ 10 mg. In two instances, uptake of 111In occurred in previously undiagnosed sites. The pharmacokinetics of MoAb were analyzed at each dose level. At the 5 mg dose, the terminal phase half-life for111In in plasma was 24.5 ± 2.7 hours. The apparent volume of distribution (Vd) wa 4.03 ± .5l similar to the plasma value, and the calculated clearance rate for 111In label was 0.259 ± 0.002 ml/kg/min. Mean urinary excretion of 111In label was 8.7 ± 0.6% of the administered dose over 48 hours after administration. The calculated pharmacokinetic parameters were independent of antibody dose. In contrast to previous studies with other anti-melanoma MoAb, ZME 018 was cleared more rapidly from plasma. Tumor localization occurred in a significant number of patients especially at MoAb doses above 2.5 mg.

AB - An 111Indium (111In)-labeled MoAb ZME 018 which reacts with a 240 Kd melanoma-associated antigen was administered to 12 patients with metastatic melanoma. MoAb was coupled to 5 mCi 111In and infused over 2 h at doses of 2.5 mg (5 pts). 5 mg (5 pts), and 10 mg (2 pts). Total body tomograms and region of interest scans were performed at 2, 24 and 72 hours post infusion. No adverse side effects were noted. There was rapid blood pool distribution to spleen, bone, bone marrow, liver, and testes. Tumor sites could be visualized as early as 24 hours but were more easily seen at 72 hours due to less background radioactivity. Seventeen of 41 (41%) previously documented metastases imaged. More sites imaged with increasing concentrations of MoAb, i.e., 25% @ 2.5 mg; 67% @ 5 mg; 75% @ 10 mg. In two instances, uptake of 111In occurred in previously undiagnosed sites. The pharmacokinetics of MoAb were analyzed at each dose level. At the 5 mg dose, the terminal phase half-life for111In in plasma was 24.5 ± 2.7 hours. The apparent volume of distribution (Vd) wa 4.03 ± .5l similar to the plasma value, and the calculated clearance rate for 111In label was 0.259 ± 0.002 ml/kg/min. Mean urinary excretion of 111In label was 8.7 ± 0.6% of the administered dose over 48 hours after administration. The calculated pharmacokinetic parameters were independent of antibody dose. In contrast to previous studies with other anti-melanoma MoAb, ZME 018 was cleared more rapidly from plasma. Tumor localization occurred in a significant number of patients especially at MoAb doses above 2.5 mg.

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