A Comparison of the Cyclic Anhydride and Mixed Anhydride Methods for ¹¹¹In-DTPA Chelation to Monoclonal Antibodies

Summary

The cyclic anhydride (CA) and the mixed anhydride (MA) of DTPA were synthesized and used to chelate ¹¹¹In to an antimelanoma monoclonal antibody. The CA and MA methods showed mean labeling efficiencies of 25.7 and 20.5%, respectively (p = NS). The binding efficiency of labeled antibody to human melanoma cells in tissue culture also was similar (x̄ = 52 and 50%, respectively, p = NS), as was tumor uptake in nude mice at 96 hrs post-injection (16%-CA vs 12%-MA). The method required less complicated chemical syntheses, much less preparation time, and the product was stable over a much longer period. The results suggest that the CA method is preferable for bifunctional chelate labeling of monoclonal antibodies with ¹¹¹In-DTPA.

Zusammenfassung

Das zyklische Anhydrid (CA) und das gemischte Anhydrid (MA) des DTPA wurden synthetisiert und angewandt, um ¹¹¹In mit einem Antimelanom monoklonalen Antikörper zu chelatisieren. Beide Methoden zeigten durchschnittliche Markierungsausbeuten von 25,7 bzw. 20,5% (p = n.s.). Die Markierungsausbeute markierter Antikörper mit menschlichen Melanomzellen in Zellkulturen war ähnlich (x̄ = 52 bzw. 50%, p = n.s.), wie auch die Tumoraufnahme in Nacktmäusen 26 Std. nach Injektion (16% CA vs. 12% MA). Die CA-Methode erforderte weniger komplizierte chemische Synthesen, eine kürzere Vorbereitung, und das Produkt war viel länger stabil. Die Ergebnisse zeigen, daß die CA-Methode für die bifunktionelle Markierung monoklonaler Antikörper mit ¹¹¹In-DTPA vorzuziehen ist.

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