Development of Receptor-Targeted Imaging Agents: Integrated Gallium Complexes and Conjugated Cyclopentadienyl Tricarbonyl Rhenium and Technetium Complexes

Abstract

As the preferred radionuclide for use in Single Photon Emission Computed Tomography (SPECT) imaging is 99mTc, the development of 99mTc-labeled phenyl-tropane analogs with high affinity for the dopamine transporter (DAT) would provide a useful tool for imaging disorders in this transporter system, such as clinical diagnosis of Parkinson's disease. The Direct Double Ligand Transfer (DLT) reaction was developed and utilized in the preparation of several cyclopentadienyltricarbonyl rhenium phenyl-tropanes. N-[4-Oxo-4-cyclopentadienyltricarbonyl rhenium butyl]-2beta-carbomethoxy-[3beta-(4-iodophenyl)] tropane was tested for affinity to the dopamine transporter in rat brain tissue homogenate as a surrogate to the radiolabeled congener. The computed DAT affinity of the rhenium compound was 5.95 +/- 0.93 nM. Regional cerebral uptake and distribution of the technetium-99m congener was evaluated in vivo in mouse brain. At 60 and 90 min after i.v. injection of the technetium compound, the mouse striatum/cerebellum radioactivity ratio was 2.0 and 2.3, and was reduced to unity in presence of beta-CIT at 60 min. The findings show for the first time that a cyclopentadienyltricarbonyltechnetium complex can penetrate mammalian brain tissue and differentially label DAT-rich corpus striatum.