title: Labeling of monoclonal antibodies with rhenium-186 using the MAG3 chelate for radioimmunotherapy of cancer: a technical protocol.
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 immunoreactivity or alter the in vivo biodistribution characteristics of the immunoconjugate, making this labeling procedure suitable for general clinical application.
authors.affiliation: Radio-Nuclide-Center (RNC), Free University, Amsterdam, The Netherlands.
authors.forename: G W
authors.initials: GW
authors.lastname: Visser
authors.forename: M
authors.initials: M
authors.lastname: Gerretsen
authors.forename: J D
authors.initials: JD
authors.lastname: Herscheid
authors.forename: G B
authors.initials: GB
authors.lastname: Snow
authors.forename: G
authors.initials: G
authors.lastname: van Dongen
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016499:Radioimmunotherapy; D011868:Radioisotopes / Q000627:therapeutic use*; D012211:Rhenium / Q000627:therapeutic use*; D017263:Technetium Tc 99m Mertiatide / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D011868:Radioisotopes; D017263:Technetium Tc 99m Mertiatide; D012211:Rhenium