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Labeling of Monoclonal Antibodies with Rhenium-186 Using the MAG3 Chelate for Radioimmunotherapy of Cancer: A Technical Protocol

Radio-Nuclide-Center (RNC), Free University
Department of Otolaryngology/Head and Neck Surgery, Free University Hospital, Amsterdam, The Netherlands

Correspondence: For correspondence or reprints contact: Gerard W.M. Visser, PhD, Radio-Nuclide-Center (RNC), Free University, P.O. Box 7161, 1007 MC Amsterdam, The Netherlands.

ABSTRACT

A detailed technical protocol is provided for reproducible and aseptical production of stable ¹⁸⁶Re-monoclonal antibody conjugates. Labeled Mab E48 IgG and its F(ab')₂ fragment which are promising candidates for radioimmunotherapy of squamous cell carcinoma of the head and neck were used for evaluation. S-benzoylmercaptoacetyltriglycine (S-benzoyl-MAG3) was used as a precursor. Rhenium-186-MAG3 was prepared via a unique solid-phase synthesis, after which known strategies for esterification and conjugation to Mab IgG/F(ab')₂ were applied. The biodistribution of ¹⁸⁶Re-E48 F(ab')₂ in tumor-bearing nude mice was found to be comparable to that of analogously labeled ^99mTc-E48 F(ab')₂ or ¹³¹I-E48 F(ab')₂, indicating that the intrinsic behavior of the antibody remains preserved when using this labeling technique. Radiolytic decomposition of ¹⁸⁶Re-E48 IgG/F(ab')₂ solutions of 10 mCi · ml^–1 was effectively reduced by the antioxidant ascorbic acid. Upon increase of the Re-MAG3 molar amount, a conjugation of seven to eight Re-MAG3 molecules per Mab molecule was generally the maximum ratio that could chemically be obtained. Such a ratio did not impair the Immuno-reactivity or alter the in vivo biodistribution characteristics of the immunoconjugate, making this labeling procedure suitable for general clinical application.

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