Cyclopentadienyl tricarbonyl complexes of 99mTC for the in vivo imaging of the serotonin 5-HT1A receptor in the brain


Cyclopentadienyl tricarbonyl complexes of 99mTC for the in vivo imaging of the serotonin 5-HT1A receptor in the brain

Saidi, M.; Kretzschmar, M.; Seifert, S.; Bergmann, R.; Pietzsch, H.-J.

The present interest in the 5-HT1A receptor is due to its implicated role in several major neuropsychiatric disorders such as depression, eating disorders and anxiety. For the diagnosis of these pathophysiological processes it is important to have radioligands in hand able to specifically bind on the 5-HT1A receptor in order to allow brain imaging. Due to the optimal radiation properties of 99mTc there is a considerable interest in the development of 99mTc radiopharmaceuticals for imaging serotonergic CNS receptors using single-photon emission tomography (SPET) [1,2].
Here we introduce two cyclopentadienyl technetium tricarbonyl conjugates of piperidine derivatives which show high accumulation of radioactivity in brain areas rich in 5-HT1A receptors. The complexes have been synthesized starting from the ferrocene complexes N-(alkyl)piperidino-4-[bispentahaptocyclopentadenyl)iron]carboxylate (with alkyl = methyl, isopropyl) [3]. Their chemical identity was confirmed by chromato-graphic methods and electrospray mass spectrometry.
The in vivo uptake of the 99mTc ligands in the whole rat brain and into brain regions was investigated. To determine the pharmacological specificity and selectivity, a group of rats was pretreated with several receptor ligands. The evaluation was carried out by quantitative digital ex vivo autoradiography.
Furthermore, we report the in vitro receptor affinity and biodistribution of the two candidates in order to demonstrate the suitability of the concept and to elucidate the influence of the building blocks on the biobehaviour of the complexes.

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Publ.-Id: 6461