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153 Sm and  166 Ho complexes with two series of tetraazamacrocyclic ligands containing methylcarboxylate and/or methylphosphonate pendant arms were synthesized and their charge, lipophilicity, protein binding and  in vitro  and  in vivo  behaviour evaluated. The first series has the same backbone, a 14-membered tetraazamacrocycle containing a pyridine unit with different pendant arms, namely methylcarboxylates (ac 3 py14) or methylphosphonates (MeP 2 py14 and P 3 py14). The second series comprises 12- to 14-membered tetraazamacrocycles having methylcarboxylates and/or methylphosphonates as pendant arms ( trans -DO2A2P, TRITA, TRITP, TETA and TETP). The  153 Sm/ 166 Ho complexes with the 14-membered tetraazamacrocycles containing the pyridine unit are neutral, hydrophilic, have a significant plasmatic protein binding, are unstable  in vivo  and present a slow rate of radioactivity excretion and high hepatic retention.  153 Sm/ 166 Ho complexes with the 12- to 14-membered tetraazamacrocycles are quantitatively prepared, except those with TETP. These complexes are hydrophilic, have an overall negative charge and present a medium to low plasmatic protein binding.

Biological evaluation of 153 Sm and 166 Ho complexes with tetraazamacrocycles containing methylcarboxylate and/or methylphosphonate pendant arms