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Titolo:
SYNTHESIS AND CHARACTERIZATION OF TC-99M-LABELED TROPANES AS DOPAMINETRANSPORTER-IMAGING AGENTS
Autore:
MEEGALLA SK; PLOSSL K; KUNG MP; CHUMPRADIT S; STEVENSON DA; KUSHNER SA; MCELGIN WT; MOZLEY PD; KUNG HF;
Indirizzi:
UNIV PENN,DEPT RADIOL,3700 MARKET ST,ROOM 305 PHILADELPHIA PA 19104 UNIV PENN,DEPT RADIOL PHILADELPHIA PA 19104 UNIV PENN,DEPT PHARMACOL PHILADELPHIA PA 19104 UNIV PENN,DEPT PSYCHIAT PHILADELPHIA PA 19104
Titolo Testata:
Journal of medicinal chemistry
fascicolo: 1, volume: 40, anno: 1997,
pagine: 9 - 17
SICI:
0022-2623(1997)40:1<9:SACOTT>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON EMISSION TOMOGRAPHY; SELECTIVE COMPOUNDS; PARKINSONS-DISEASE; OXOMETAL COMPLEXES; RECEPTOR-BINDING; BABOON BRAIN; TECHNETIUM; AFFINITY; COCAINE; RHENIUM(V);
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
43
Recensione:
Indirizzi per estratti:
Citazione:
S.K. Meegalla et al., "SYNTHESIS AND CHARACTERIZATION OF TC-99M-LABELED TROPANES AS DOPAMINETRANSPORTER-IMAGING AGENTS", Journal of medicinal chemistry, 40(1), 1997, pp. 9-17

Abstract

In the development of novel Tc-99m-labeled tropane derivatives as dopamine transporter (reuptake site)-imaging agents, a series of neutral and lipophilic complexes containing bis(aminoethanethiol) as a neutralcomplexing moiety for a [Tc-99m]TcO3+ center core was successfully prepared. Biological evaluation of the Tc-99m-labeled complexes 13-16 ascentral nervous system (CNS) dopamine transporter-imaging agents was reported. Synthesis of the tropane derivatives was achieved by stepwise reactions adding two aminoethanethiol units. The final free thiol ligands were obtained by deblocking the 4-methoxybenzyl protecting groupwith Hg(OAc)(2) to obtain trifluoroacetate salts. All of the Tc-99m complexes, with the exception of 16, displayed good initial brain uptake and selective uptake in the striatal area, where dopamine transporters are concentrated. One of the compounds, .2.1]oct-2-yl]methyl](2-mercaptoethyl)amino]ethyl] amino]ethanethiolato-(3-)-N2,N2',S2,S2'] oxo-[1R-(exo-exo)]-[Tc-99m]technetium, [Tc-99m]TRODAT-1 (13), displayed thehighest initial uptake in rat brain (0.4% at 2 min post iv injection); the striatal/cerebellar (ST/CB) ratio reached 2.8 at 60 min after aniv injection. The specific uptake in rat brain can be blocked by pretreating rats with a competing dopamine transporter binding agent, beta-CIT (RTI-55, 2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane iv, 1 mg/kg), which reduced the regional brain uptake ratio (ST/CB) to 1.2. In contrast, the specific striatal uptake was not affected by pretreating rats with st noncompeting ligand, haldol (iv, 1 mg/kg). After an ivinjection of 9 mCi of [Tc-99m]TRODAT-1 (13), in vivo images of baboonbrain using single-photon emission-computed tomography exhibited excellent localization in striatum (basal ganglia), where dopamine neuronsare known to be concentrated. This series of compounds may provide a convenient source of short-lived imaging agents for routine diagnosis of CNS diseases (i.e., Parkinson's disease) in which changes in the dopamine transporter concentration are implicated.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 19/01/20 alle ore 06:23:05