Synthesis of new bifunctional chelating agents: (1R*,2R*,4S*)-4-isothiocyanatocyclohexane-1,2-diamine-N,N,N′,N′-tetrakismethanephosphonic acid (4-ICMP) and (1R*,2R*,4S*)-4-isothiocyanatocyclohexane-1,2-diamine-N,N,N′,N′-tetrakisethanephosphonic acid (4-ICEP)

Abstract

Immunotherapy with radiolabelled antibodies should allow fairly specific targeting of certain cancers. Although ¹⁵³Sm possesses favourable radiophysical characteristics for such therapy, a lack of radiolabelling stability in vivo limits its application. Yet the use of phosphonic semi-rigid bifunctional chelating agents (BCA) can improve its stability. Syntheses of (1R*,2R*,4S*)-4-isothiocyanatocyclohexane-1,2-diamine-N,N,N′,N′-tetrakismethanephosphonic acid (4-ICMP) and (1R*,2R*,4S*)-4-isothiocyanatocyclohexane-1,2-diamine-N,N,N′,N′-tetrakisethanephosphonic acid (4-ICEP) are described in this paper. The complexing properties of these two compounds has been confirmed by labelling with ¹⁵³Sm. A novel synthetic approach involving the introduction of methanephosphonic functions has also been developed.