Preparation and biodistribution of 1-((2-methoxyphenyl) piperazine)ferrocenecarboxamide labeled with technetium-99m as a potential brain receptor imaging agent.

The goal of this study is to develop a novel brain receptor imaging agent. This study reports the synthesis, characterization and the biological evaluation of 1-((2-methoxyphenyl) piperazine)ferrocenecarboxamide labeled with technetium-99 m ((99m)Tc-MP). The (99m)Tc-MP was obtained quickly (radiolabelling time < 5 min), in 90% yield. The (99m)Tc-complex, characterized by HPLC (20-50% ACN of 0 at 5 min then 50% ACN of 5 at 17 min to finally with 50 at 20% ACN of 17 at 20 min), is stable, neutral and lipophilic enough to cross the blood-brain barrier which was confirmed by octanol/water partition coefficient (LogP = 1.82). In vivo biodistribution indicated that this complex had exceptional brain uptake (2.47% ID/g at 5 min and 0.75% ID/g at 60 min). The distribution of the activity at 15 min post-injection in various rat brain regions showed a higher accumulation in the hippocampus area. After blocking with 8-hydroxy-2-(dipropylamino) tetralin, the uptake of hippocampus was decreased significantly from 0.87% ID/g to 0.21% ID/g at 15 min p.i., while the cerebellum had no significant decrease. The new (99m)Tc-cyclopentadienyltricarbonyl technetium complex reported here showed promising biological results, making it an interesting starting point for the development of a new (99m)Tc-complex as brain receptor imaging agent.

Preliminary studies of acetylcholinesterase activity in the rat brain using N-phenylferrocenecarboxamide labelled by the technetium-99m.

There is currently great interest in developing radiolabeled substrates for acetylcholinesterase that would be useful in the in vivo imaging of patients with Alzheimer's disease. The reduction of acetylcholinesterase (AChE) activity in the brain has been measured in dementia disorders such as Alzheimer's disease and dementia with Lewy bodies using (11)C and (18)F-labeled acetylcholine analogues. Our aim was to develop a new 99mTc-labeled acetylcholine analogue: N-phenylferrocenecarboxamide labelled with technetium-99m (99mTc-TPCC) to study acetylcholinesterase activity. In vivo and in vitro studies demonstrated that the labelled compound was a substrate for acetylcholinesterase. The hydrolytic rate of this substrate was measured and the specificity was evaluated using the inhibitor BW 284 C51. In rat experiments, the 99mTc-TPCC showed desirable properties for studying the acetylcholinesterase in the rat brain: high hydrolytic rate and a moderate specificity of the substrate for acetylcholinesterase.

A 1-methyl-4-piperidinyl cytectrene carboxylate labeled by the technetium 99m, a radiotracer for rat brain acetylcholinesterase activity.

Alzheimer's disease (AD) is a degenerative neurological disorder that causes progressive and irreversible loss of connections between brain cells and loss of mental functions. Clinical and postmortem studies show that the biochemical changes in brains of AD patients include decrease in acetylcholinesterase (AChE) activity. Our aim was to study AChE activity using piperidinyl ester labelled with technetium-99m. In vivo and in vitro studies demonstrated that labelled piperidinyl ester was a substrate for AChE. The hydrolytic rate of this substrate was measured and the specificity was evaluated using the inhibitor BW284c51. The rhenium analogues of the technetium-labelled substrate were used to determine the affinity constant (K(m)) and the maximum reaction velocity (V(max)) because of the high specific activity of technetium. The high hydrolytic rate and high specificity of the substrate for AChE make it suitable as an in vivo radiotracer for studying AChE activity in the brain.