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Clinical Parameters Related to Optimal Tumor Localization of Indium-111-Labeled Mouse Antimelanoma Monoclonal Antibody ZME-018

Departments of Clinical Immunology and Biological Therapy, Nuclear Medicine, and Medical Oncology, UT M.D. Anderson Hospital and Tumor Institute, Houston, Texas
Hybritech, Incorporated, San Diego, California

Correspondence: For reprints contact: James Lee Murray, MD, Clinical Immunology, Box 41, M. D. Anderson Hospital and Tumor Institute, 6723 Bertner Ave., Houston, TX 77030.

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.