Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
[TC-99M]TRODAT-1 - A NOVEL TC-99M COMPLEX AS A DOPAMINE TRANSPORTER IMAGING AGENT
Autore:
KUNG MP; STEVENSON DA; PLOSSL K; MEEGALLA SK; BECKWITH A; ESSMAN WD; MU M; LUCKI I; KUNG HF;
Indirizzi:
UNIV PENN,DEPT RADIOL,3700 MARKET ST,ROOM 305 PHILADELPHIA PA 19104 UNIV PENN,DEPT PSYCHIAT PHILADELPHIA PA 19104 UNIV PENN,DEPT PHARMACOL PHILADELPHIA PA 19104
Titolo Testata:
European journal of nuclear medicine
fascicolo: 4, volume: 24, anno: 1997,
pagine: 372 - 380
SICI:
0340-6997(1997)24:4<372:[-ANTC>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
POSITRON EMISSION TOMOGRAPHY; PARKINSONS-DISEASE; REUPTAKE SITES; BRAIN; BINDING; INVIVO; COCAINE; RECEPTOR; AUTORADIOGRAPHY; AMPHETAMINE;
Keywords:
STRIATUM; SINGLE-PHOTON EMISSION TOMOGRAPHY; DOPAMINE NEURON; 6-OH-DOPAMINE; AUTORADIOGRAPHY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
42
Recensione:
Indirizzi per estratti:
Citazione:
M.P. Kung et al., "[TC-99M]TRODAT-1 - A NOVEL TC-99M COMPLEX AS A DOPAMINE TRANSPORTER IMAGING AGENT", European journal of nuclear medicine, 24(4), 1997, pp. 372-380

Abstract

Technetium-99m is the most commonly used radionuclide in routine nuclear medicine imaging procedures. Development of Tc-99m-labeled receptor-specific imaging agents for studying the central nervous system is potentially useful for evaluation of brain function in normal and disease states. A novel Tc-99m-labeled tropane derivative, [Tc-99m]TRODAT-1, which is useful as a potential CNS dopamine transporter imaging agent, was evaluated and characterized. After i.v. injection into rats, [Tc-99m]TRODAT-1 displayed specific brain uptake in the rat striatal region (striatum-cerebellum/cerebellum ratio 1.8 at 60 min), where dopamine neurons are concentrated. The specific striatal uptake could be blocked by pretreating rats with a dose of competing dopamine transporterligand, beta-CIT (or RTI-55, i.v., 1 mg/kg). However, the specific striatal uptake of [Tc-99m]TRODAT-1 was not affected by co-injection of excess fi-ee ligand (TRODAT-1, up to 200 mu g per rat) or by pretreating the rats with haloperidol (i.v., 1 mg/kg), The specific uptake in striatal regions of rats that had prior 6-hydroxydopamine lesion in thesubstantia nigra area showed a dramatic reduction. The radioactive material recovered from the rat striatal homogenates at 60 min after i.v. injection of [Tc-99m]TRODAT-1 showed primarily the original compound(> 95%), a good indication of in vivo stability in brain tissue. Similar and comparable organ distribution patterns and brain regional uptakes of [Tc-99m]TRODAT-1 were obtained for male and female rats. Ex vivo autoradiography results of rat brain sections further confirmed the high uptake and retention of [Tc-99m]TRODAT-1 in the striatal region. In vitro binding studies measuring the affinity to dopamine transporters for the free ligand, TRODAT-1, and a nonradioactive rhenium derivative, Re-TRODAT-1, showed K-i values of 9.7 nM and 14.1 nM, respectively. Behavioral studies in rats using the free ligand, TRODAT-1 and Re-TRODAT-1 indicated that, unlike other tropane derivatives, they displayed no effect on locomotor activity, suggesting low toxicity. These results strongly support the conclusions that this novel Tc-99m radioligand binds selectively to dopamine transporters in the brain and that isis potentially useful for in vivo assessment of the loss of dopamine neurons in Parkinson's and other neurodegenerative diseases.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 15:51:17