Structure, stability, and biodistribution of cationic [M(CO) 3]+ (M = Re,99Tc, 99mTc) complexes with tridentate amine ligands

Article abstract of DOI:10.1081/SIM-200047534

Bifunctional chelating molecules linking the fac-[^99mTc(CO) ₃]⁺ core with targeting biomolecules are required for the development of specific diagnostic radiopharmaceuticals. Diethylenetriamine (1) and N-(pyridin-2-ylmethyl)ethane-1,2-diamine (2) both react readily with [ ^99mTc(H₂O)₃(CO)₃]⁺ in 0.9% saline at micromolar concentrations to form the cationic complexes [ ^99mTc(1)(CO)₃]⁺ (5) and [^99mTc(2) (CO)₃]⁺ (6) in quantitative yields. The crystal structures of the corresponding Re or ⁹⁹Tc complexes were determined and exhibit in particular the small size of 5. Challenging both ^99mTc complexes 5 and 6 with a 10⁴ excess of histidine or cysteine showed no decomposition or ligand exchange after 24 hours and both compounds were also stable against reoxidation to [^99mTcO₄]^-. In normal mice, complex 5 revealed a good and fast clearance from the blood, and most organs. Only limited accumulation in the large intestine was visible after 4 hours. Complex 6 was also excreted relatively quickly from the blood but retention was observed in some tissues after 4 h. In order to illustrate the potential of both ligands to be further functionalized, two derivatives containing potentially DNA binding functionalities, N-(2-Amino-ethyl)-N′- pyren-1-ylmethyl-ethane-1,2-diamine (3) and N-(quinolin-2-ylmethyl)ethane-1,2- diamine (4) were synthesized. The respective Re or ⁹⁹Tc complexes were fully characterized. Based on these results, it appears that functionalization of biomolecules with acyclic triamine ligands is biologically relevant. Complex 5 in particular could be used to mimic a terminal amino group in, e.g., a peptide due to its small size and positive charge. Copyright