Abstract
Three dithioformate ligands with methyl substituted on the piperidine rings, potassium 1‐(2‐methylpiperidine‐1‐yl)‐dithioformate (2‐mp), potassium 1‐(3‐methylpiperidine‐1‐yl)‐dithioformate (3‐mp) and potassium 1‐(4‐methylpiperidine‐1‐yl)‐dithioformate (4‐mp) were synthesized. The corresponding ^99m^Tc‐nitrido complexes were prepared in high yield (>95%) through the [^99m^TcN] intermediate and characterized by thin layer chromatography and high‐performance liquid chromatography. All the neutral ^99m^Tc‐nitrido complexes were stable under physiological conditions and lipophilic with log P values between 1.40 and 1.58. In vivo biodistribution results showed that all the ^99m^Tc‐nitrido complexes displayed high brain uptakes and long retention times. Among them, ^99m^TcN‐4mp, demonstrated the best properties for brain imaging with the brain uptake 3.40±0.24, 3.22±0.31, 2.72±0.28 and 2.22±0.18% ID/g at 5, 30, 60 and 120 min p.i., respectively. Moreover, the influence of stereochemistry of the ^99m^TcN complexes with methyl substitution on ortho, meta and para positions on piperidine ring on the biodistribution properties were investigated with B3LYP/6‐31G*(LANL2DZ for Tc) method using the Gaussian 03 program package. Copyright © 2009 John Wiley & Sons, Ltd.