Cyclic and acyclic polyamines as chelators of rhenium-186 and rhenium-188 for therapeutic use

Several polyamine ligands L(1)-L(7) were assessed as chelators for rhenium-188 (and by analogy, rhenium-186) for incorporation into the design of radiopharmaceuticals for targeted radiotherapy. Both ease of synthesis of the complexes and their kinetic stability in human serum were examined. Chelation of Re-188 by stannous reduction of perrhenate in the presence of acyclic ligands such as L(1) and L(2) (L(1) = ethylenediamine, L(2) = 1,4,8,11-tetraazaundecane) proceeded in acceptable yield (50-90%) under aqueous conditions (pH 11; 20-100 degrees C, 30 min) in a single step. In contrast, synthesis of complexes of the cyclic ligands such as L(6) (L(6) = 1,4,8,11-tetraazacyclotetradecane, cyclam) in acceptable yield (>50%) required more involved procedures including use of nonaqueous solvents. The chelates were unambiguously identified as the cationic trans-dioxorhenium(V) tertakis(amino) complexes, by chromatographic comparison with spectroscopically characterised nonradioactive samples. The complexes of tetradentate ligands L(2) and L(6) showed no evidence of degradation on incubation for up to 24 h in human serum. The complex of L(1) degraded by less than 3% under these conditions. These preliminary studies indicate that the acyclic tetradentate ligands offer an appropriate compromise between biological stability and ease of synthesis, and they have potential as chelators for rhenium in radiopharmaceuticals.