Synthesis of novel technetium-99m tricarbonyl-HBED-CC complexes and structural prediction in solution by density...

HBED-CC (N,N'-bis[2-hydroxy-5-(carboxyethyl)benzyl]ethylene diamine-N,N'-diacetic acid, L ) is a common bifunctional chelating agent in preparation of ⁶⁸Ga-radiopharmaceuticals. Due to its high stability constant for the Ga³⁺ complex (logK_GaL = 38.5) and its acyclic structure, it is well known for a rapid and efficient radiolabelling at ambient temperature with Gallium-68 and its high in vivo stability. [^99mTc][Tc(CO)₃(H₂O)₃]⁺ is an excellent precursor for radiolabelling of biomolecules. The aim of this study was to develop a novel preparation method of ^99mTc-HBED-CC complexes. In this study, HBED-CC-NI (2,2'-(ethane-1,2-diylbis((2-hydroxy-5-(3-((2-(2-nitro-1H-imidazol-1-yl)ethyl)amino)-3-oxopropyl)benzyl)-azanediyl))-diacetic acid, L ), a derivative of HBED-CC, was designed and synthesized. Both L and L were radiolabelled by [^99mTc][Tc(CO)₃(H₂O)₃]⁺ successfully for the first time. In order to explore the coordination mode of metal and chelates, non-radioactive Re(CO)₃ L and Re(CO)₃ L were synthesized and characterized spectroscopically. Tc(CO)₃ L and Tc(CO)₃ L in solution were calculated by density functional theory and were analysed with radio-HPLC chromatograms. It showed that [^99mTc]Tc(CO)₃ L forms two stable diastereomers in solution, which is similar to those of [⁶⁸Ga]Ga-HBED-CC complexes. Natural bond orbital analysis through the natural population charges revealed a charge transfer between [^99mTc][Tc(CO)₃]⁺ and L or L . The experimental results showed that tricarbonyl technetium might form stable complex with HBED-CC derivatives, which is useful for the future application of using HBED-CC as a bifunctional chelating agent in developing new ^99mTc-radiopharmaceuticals as diagnostic imaging agents.