Clinical parameters related to optimal tumor localization of indium-111-labeled mouse antimelanoma monoclonal antibody ZME-018

J. L. Murray, M. G. Rosenblum, L. Lamki, H. J. Glenn, Z. Krizan, E. M. Hersh, C. E. Plager, R. M. Bartholomew, M. W. Unger, D. J. Carlo

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Abstract

Radioimmunolocalization of an 111In-labeled mouse antimelanoma monoclonal antibody (MoAb), ZME-018, was examined in 21 patients with metastatic malignant melanoma. Each patient received a single i.v. infusion of MoAb at concentrations ranging from 1 mg to 20 mg, coupled to 5 mCi 111In by the chelating agent DPTA. No toxicity was observed in any patient. Total-body and regions of interest scans performed at 4, 24, and 72 hr following MoAb administration revealed uptake in 63 out of 105 previously diagnosed metastases for an overall sensitivity of 60%. Uptake was consistently observed in liver/spleen, and less frequently in bowel testes, axillae and bone. Sensitivity of detection increased significantly at doses of MoAb above 2.5 mg, with 74% of lesions imaging at 20 mg/5 mCi compared with 29% at 2.5 mg/5 mCi (p<0.005). A significant correlation was observed between tumor uptake of 111In-MoAb conjugate and increasing tumor size. Soft-tissue lesions such as skin and lymph node metastases were imaged to a greater extent (76%) than visceral metastases (19%). In five of six patients, biopsies obtained from 3 days to 14 days after MoAb administration showed antibody present on tumor cells as demonstrated by flow cytometry and/or radioimmunoassay. Human anti-murine immunoglobulin responses were observed in seven of 17 patients studied. Mean plasma clearance of ZME-018 was prolonged with a T( 1/2 ) of 24.7 hr and increased slightly with increasing MoAb dose. Urinary excretion of 111In averaged 12.4% of the injected dose over 48 hours. Radioimmunolocalization of melanoma with 111In-labeled ZME-018 appears feasible. The sensitivity of the technique was related to dose, tumor size, and disease site.

Original languageEnglish
Pages (from-to)25-33
Number of pages9
JournalJournal of Nuclear Medicine
Volume28
Issue number1
Publication statusPublished - 1987

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Indium
Monoclonal Antibodies
Neoplasms
Neoplasm Metastasis
Melanoma
Body Regions
Axilla
Chelating Agents
Radioimmunoassay
Testis
Immunoglobulins
Flow Cytometry
Spleen
Lymph Nodes
Biopsy
Bone and Bones
Skin
Antibodies
Liver

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology

Cite this

Murray, J. L., Rosenblum, M. G., Lamki, L., Glenn, H. J., Krizan, Z., Hersh, E. M., ... Carlo, D. J. (1987). Clinical parameters related to optimal tumor localization of indium-111-labeled mouse antimelanoma monoclonal antibody ZME-018. Journal of Nuclear Medicine, 28(1), 25-33.

Clinical parameters related to optimal tumor localization of indium-111-labeled mouse antimelanoma monoclonal antibody ZME-018. / Murray, J. L.; Rosenblum, M. G.; Lamki, L.; Glenn, H. J.; Krizan, Z.; Hersh, E. M.; Plager, C. E.; Bartholomew, R. M.; Unger, M. W.; Carlo, D. J.

In: Journal of Nuclear Medicine, Vol. 28, No. 1, 1987, p. 25-33.

Research output: Contribution to journalArticle

Murray, JL, Rosenblum, MG, Lamki, L, Glenn, HJ, Krizan, Z, Hersh, EM, Plager, CE, Bartholomew, RM, Unger, MW & Carlo, DJ 1987, 'Clinical parameters related to optimal tumor localization of indium-111-labeled mouse antimelanoma monoclonal antibody ZME-018', Journal of Nuclear Medicine, vol. 28, no. 1, pp. 25-33.
Murray, J. L. ; Rosenblum, M. G. ; Lamki, L. ; Glenn, H. J. ; Krizan, Z. ; Hersh, E. M. ; Plager, C. E. ; Bartholomew, R. M. ; Unger, M. W. ; Carlo, D. J. / Clinical parameters related to optimal tumor localization of indium-111-labeled mouse antimelanoma monoclonal antibody ZME-018. In: Journal of Nuclear Medicine. 1987 ; Vol. 28, No. 1. pp. 25-33.
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abstract = "Radioimmunolocalization of an 111In-labeled mouse antimelanoma monoclonal antibody (MoAb), ZME-018, was examined in 21 patients with metastatic malignant melanoma. Each patient received a single i.v. infusion of MoAb at concentrations ranging from 1 mg to 20 mg, coupled to 5 mCi 111In by the chelating agent DPTA. No toxicity was observed in any patient. Total-body and regions of interest scans performed at 4, 24, and 72 hr following MoAb administration revealed uptake in 63 out of 105 previously diagnosed metastases for an overall sensitivity of 60{\%}. Uptake was consistently observed in liver/spleen, and less frequently in bowel testes, axillae and bone. Sensitivity of detection increased significantly at doses of MoAb above 2.5 mg, with 74{\%} of lesions imaging at 20 mg/5 mCi compared with 29{\%} at 2.5 mg/5 mCi (p<0.005). A significant correlation was observed between tumor uptake of 111In-MoAb conjugate and increasing tumor size. Soft-tissue lesions such as skin and lymph node metastases were imaged to a greater extent (76{\%}) than visceral metastases (19{\%}). In five of six patients, biopsies obtained from 3 days to 14 days after MoAb administration showed antibody present on tumor cells as demonstrated by flow cytometry and/or radioimmunoassay. Human anti-murine immunoglobulin responses were observed in seven of 17 patients studied. Mean plasma clearance of ZME-018 was prolonged with a T( 1/2 ) of 24.7 hr and increased slightly with increasing MoAb dose. Urinary excretion of 111In averaged 12.4{\%} of the injected dose over 48 hours. Radioimmunolocalization of melanoma with 111In-labeled ZME-018 appears feasible. The sensitivity of the technique was related to dose, tumor size, and disease site.",
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AU - Carlo, D. J.

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N2 - Radioimmunolocalization of an 111In-labeled mouse antimelanoma monoclonal antibody (MoAb), ZME-018, was examined in 21 patients with metastatic malignant melanoma. Each patient received a single i.v. infusion of MoAb at concentrations ranging from 1 mg to 20 mg, coupled to 5 mCi 111In by the chelating agent DPTA. No toxicity was observed in any patient. Total-body and regions of interest scans performed at 4, 24, and 72 hr following MoAb administration revealed uptake in 63 out of 105 previously diagnosed metastases for an overall sensitivity of 60%. Uptake was consistently observed in liver/spleen, and less frequently in bowel testes, axillae and bone. Sensitivity of detection increased significantly at doses of MoAb above 2.5 mg, with 74% of lesions imaging at 20 mg/5 mCi compared with 29% at 2.5 mg/5 mCi (p<0.005). A significant correlation was observed between tumor uptake of 111In-MoAb conjugate and increasing tumor size. Soft-tissue lesions such as skin and lymph node metastases were imaged to a greater extent (76%) than visceral metastases (19%). In five of six patients, biopsies obtained from 3 days to 14 days after MoAb administration showed antibody present on tumor cells as demonstrated by flow cytometry and/or radioimmunoassay. Human anti-murine immunoglobulin responses were observed in seven of 17 patients studied. Mean plasma clearance of ZME-018 was prolonged with a T( 1/2 ) of 24.7 hr and increased slightly with increasing MoAb dose. Urinary excretion of 111In averaged 12.4% of the injected dose over 48 hours. Radioimmunolocalization of melanoma with 111In-labeled ZME-018 appears feasible. The sensitivity of the technique was related to dose, tumor size, and disease site.

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