Structure, Stability, and Biodistribution of Cationic [M(CO)3]+ (M = Re, 99Tc, 99mTc) Complexes with Tridentate Amine Ligands

• Published in: Synthesis and reactivity in inorganic, metal-organic, and nano-metal chemistry metal-organic, and nano-metal chemistry, 2005-01, Vol.35 (1), p.27-34
• Main Authors: Häfliger, Pascal, Mundwiler, Stefan, Andócs, Gábor, Balogh, Lajos, Bodo, Katalin, Ortner, Kirstin, Spingler, Bernhard, Alberto, Roger
• Format: Article
• Language: English
• Subjects: 99m; biodistribution; bioorganometallic; imaging agents; labeling; radiopharmacy; rhenium; Techentium
• ISSN: 1553-3174; 1553-3182
• DOI: 10.1081/SIM-200047534

Bifunctional chelating molecules linking the fac-[ 99m Tc(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 [ 99m Tc(H 2 O) 3 (CO) 3 ] + in 0.9% saline at micromolar concentrations to form the cationic complexes [ 99m Tc(1)(CO) 3 ] + (5) and [ 99m Tc(2)(CO) 3 ] + (6) in quantitative yields. The crystal structures of the corresponding Re or 99 Tc complexes were determined and exhibit in particular the small size of 5. Challenging both 99m Tc complexes 5 and 6 with a 10 4 excess of histidine or cysteine showed no decomposition or ligand exchange after 24 hours and both compounds were also stable against reoxidation to [ 99m TcO 4 ] − . 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 99 Tc 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. We thank Mallinckrodt Med. BV, Petten, NL for financial support.