BACKGROUND: The aim of this work was the development of a sufficient method for synthesis and radiolabelling with technetium- 99m a new class of compounds as potential ligands for brain imaging.
METHODS: The synthesis of new ligands with the structure of 2-(N-arylmethylideneamine) benzophenone oxime (6?10) based on the cyclocondensation of appropriate 2-aminobenzophenone oxime 1?2 with respective aldehydes 3?4 or ketone 5 in acidic conditions. During our experiments in dependencies from the reaction conditions, compounds with the structure of Schiff?s bases (6?10) or 3N-oxides 1,2-dihrydroquinazoline derivatives were obtained. Labelling of compounds 6 or 7 with technetium- 99m was done by stannous chloride reduction according to two methods (in ethyl alcohol or in chloroform) following the radiolabelling method of HM-PAO. The complex ^99mTc-HM-PAO was the leading compound in our computational calculations with geometrical optimisation of a molecule. Using molecular modelling (semi-empirical method ZINDO) we have determined the electrostatic potential for the obtained ligands. Additionally we have calculated total energy,binding energy, heat of formation and several 3D-QSAR parameters for theoretically possible complexes of ^99mTc with the obtained ligands.
RESULTS: As a result of our experiments a method of a synthesis of new compounds 6 and 7 has been developed. Computational calculations were performed using the HyperChem 4.5 program. These calculations confirmed our hypothesis that only ligand 7 is able to form a complex with ^99mTc and this complex possesses lipophilic properties.
CONCLUSIONS: Complex ^99mTc-7, due to its lipophilic properties, is a potential radiopharmaceutical for the brain imaging.