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Clinical Experience with Rhenium-186-Labeled Monoclonal Antibodies for Radioimmunotherapy: Results of Phase I Trials

Departments of Radiology and Medicine, Virginia Mason Medical Center, Seattle, Washington
NeoRx Corporation, Seattle, Washington
Health Physics Department, Battelle Pacific Northwest Laboratories, Richland, Washington

Correspondence: For reprints contact: Hazel B. Breitz, MD and Paul L. Weiden, MD, Virginia Mason Medical Center, P.O. Box 900, C2-S, Seattle, WA 98111.

ABSTRACT

Rhenium is a radionuclide with physical and chemical properties suitable for radioimmunotherapy. Two Phase I trials were earned out using ¹⁸⁶Re-labeled murine monoclonal antibodies. Patients with refractory metastatic epithelial carcinoma received single doses of either ¹⁸⁶Re-labeled intact NR-LU-10, a pancarcinoma antibody, 25-120 mCi/m² (n = 15) or ¹⁸⁶Re-labeled F(ab')₂ fragment of NR-CO-02, an anti-CEA variant antibody, 25-200 mCi/m² (n = 31). Prior to radioimmunotherapy, tumor localization of antibody was confirmed by ^99mTc-labeled NR-LU-10 Fab or ^99mTc-labeled NR-CO-02 F(ab')₂ imaging. Dose-limiting myelosuppression was observed at 120 mCi/m² following ¹⁸⁶Re-NR-LU-10 intact antibody and at 150 mCi/m² following NR-CO-02 F(ab')₂ fragment in heavily pretreated patients. In patients with minimal prior therapy, a maximum tolerated dose for NR-CO-02 F(ab')₂ was not reached by 200 mCi/m². Non-marrow toxicity was minimal. Human anti-mouse antibody developed in all patients receiving intact NA-LU-10, and in 86% patients receiving F(ab')₂ NR-CO-02. One patient treated with ¹⁸⁶Re NR-CO-02 achieved a partial response. We conclude that ¹⁸⁶Re-labeled antibody can be safely administered with significant toxicity limited to marrow.

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