Biological evaluation of 153Sm and 166Ho complexes with macrocyclic ligands containing acetate pendant arms as potential agents for therapy

For the development of therapeutic radiopharmaceuticals it is essential to choose the appropriate beta-emitter as well as the carrier biomolecule. Different carrier biomolecules, namely antibodies and peptides, have been linked to different beta-emitters (153Sm, 166Ho and 177Lu) using tetraaza macrocycles as bifunctional chelators. The cavity size of these chelators, the rigidity of the macrocyclic backbone and the nature of the pendant arms seems to play an important role on the thermodynamic stability and kinetic inertness of the radiocomplexes and on their biological behaviour. In our research group we have been exploring the possibility of using tetraazamacrocycles with different cavity size, pendant arms and rigidity for preparing 153Sm and 166Ho complexes useful for therapeutical applications and/or bone pain palliation. In this communication we present the results obtained when we reacted trita and teta with 153Sm and 166Ho. The complexes are formed in good yields (> 98%), are hydrophilic and present an overall negative charges, as well as low plasmatic protein binding. Good in vitro stability in physiological media and human serum was also found for all the complexes. The biodistribution studies in mice are also presented and have shown that 153Sm/166Ho-trita and 166Ho-teta have rapid tissue clearance, comparably to the corresponding dota complexes. In contrast, 153Sm-teta has a significant lower total excretion and a significant liver and muscle uptake. Our results indicate that 153Sm/166Ho-trita form very stable complexes in vivo. However, teta, which has a larger cavity size, forms less stable complexes with the larger ion Sm3+. The biological profile of 153Sm/166Ho-trita is very interesting for the evaluation of these complexes as therapeutical agents when conjugated to biomolecules