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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Tc-99m-labeled tropanes as dopamine transporter imaging agents.

The development of novel Tc-9m-labeled tropane derivatives as dopamine transporter imaging agents is reported. A series of neutral and lipophilic conjugated complexes, containing N-(alkylthiolato)-tropane, aminobis(ethylthiolato), and a [99mTc]TcO3+ center core, were prepared and evaluated as central nervous system (CNS) dopamine transporter imaging agents in rats. One of the compounds, [99mTC]technetium, [methyl 3-(4-chlorophenyl)-8-(2-mercaptoethyl-8-azabicyclo [3.2.1]octane-2-carboxylato-S][[2,2'-(methylimino)bis[eth anethiolato]] (2-)-N,S,S']oxo (25), displayed low initial uptake in rat brain (0.1% at 2 min post i.v. injection); the striatal/cerebellar (ST/CB) ratio reached 3.50 at 60 min after an i.v. injection. The specific uptake can be blocked by pretreating rats with a competing dopamine transporter binding agent, beta-CIT (RTI-55, N-methyl-2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane; i.v. 1 mg/kg), which reduced the regional brain uptake ratio (ST/CB) to 1. 0. In contrast, the specific uptake in striatum was not affected by pretreating rats with a noncompeting ligand, haldol (i.v., 1 mg/kg). In vitro autoradiography of rat brain sections exhibited elevated labeling in striatum, major islands of Calleja, and olfactory tubercle regions, where dopamine neurons are known to be concentrated. This series of compounds is the first example of technetium-99m labeled CNS receptor-specific imaging agents and may provide a convenient source of short-lived imaging agents for routine diagnosis of CNS abnormality in conjunction with single photon emission computed tomography.[1]

References

  1. Tc-99m-labeled tropanes as dopamine transporter imaging agents. Meegalla, S., Plössl, K., Kung, M.P., Chumpradit, S., Stevenson, D.A., Frederick, D., Kung, H.F. Bioconjug. Chem. (1996) [Pubmed]
 
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