CYCLIC AND ACYCLIC POLYAMINES AS CHELATORS OF RE-186 AND RE-188 FOR THERAPEUTIC USE

Several polyamine ligands L(1)-L(7) were assessed as chelators for rhe nium-188 (and by analogy, rhenium-186) for incorporation into the desi gn of radiopharmaceuticals for targeted radiotherapy. Both ease of syn thesis of the complexes and their kinetic stability in human serum wer e 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) = ethylen ediamine, L(2) = 1,4,8,11-tetraazaundecane) proceeded in acceptable yi eld (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 includi ng use of nonaqueous solvents. The chelates were unambiguously identif ied as the cationic trans-dioxorhenium(V) tertakis(amino) complexes, b y chromatographic comparison with spectroscopically characterised nonr adioactive samples. The complexes of tetradentate ligands L(2) and L(6 ) showed no evidence of degradation on incubation for up to 24 h in hu man serum. The complex of L(1) degraded by less than 3% under these co nditions. These preliminary studies indicate that the acyclic tetraden tate ligands offer an appropriate compromise between biological stabil ity and ease of synthesis, and they have potential as chelators for rh enium in radiopharmaceuticals.