¹²³I-NKJ64: a novel single photon emission computed tomography radiotracer for imaging the noradrenaline transporter in brain.
Synapse
; 65(7): 658-67, 2011 Jul.
Article
em En
| MEDLINE
| ID: mdl-21157929
ABSTRACT
Dysregulation of noradrenergic function has been implicated in a variety of psychiatric and neurodegenerative disorders, including depression and Alzheimer's disease. The noradrenaline transporter (NAT) is a major target for antidepressant drugs, including reboxetine, a selective noradrenaline reuptake inhibitor. Therefore, the development of a radiotracer for imaging of the NAT is desirable. In this study, NKJ64, a novel iodinated analog of reboxetine, was radiolabeled and evaluated as a potential single photon emission computerized tomography (SPECT) radiotracer for imaging the NAT in brain. Biological evaluation of the novel radiotracer, ¹²³/¹²5I-NKJ64, was carried out in rats using in vitro ligand binding assays; in vitro and ex vivo autoradiography; in vivo biodistribution studies and ex vivo pharmacological blocking studies. ¹²5I-NKJ64 displayed saturable binding with high affinity for NAT in cortical homogenates (K(D) = 4.82 ± 0.87 nM, mean ± SEM, n = 3). In vitro and ex vivo autoradiography showed the regional distribution of ¹²³I-NKJ64 binding to be consistent with the known density of NAT in brain. Following i.v. injection there was rapid uptake of ¹²³I-NKJ64 in brain, with maximum uptake of 2.93% ± 0.14% (mean ± SEM, n = 3) of the injected dose. The specific to nonspecific ratio (locus coeruleuscaudate putamen) of ¹²³I-NKJ64 uptake measured by ex vivo autoradiography was 2.8 at 30 min post i.v. injection. The prior administration of reboxetine significantly reduced the accumulation of ¹²³I-NKJ64 in the locus coeruleus (>50% blocking). The data indicate that further evaluation of ¹²³I-NKJ64 in nonhuman primates is warranted in order to determine its utility as a SPECT radiotracer for imaging of NAT in brain.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Tomografia Computadorizada de Emissão de Fóton Único
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Morfolinas
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Compostos Radiofarmacêuticos
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Proteínas da Membrana Plasmática de Transporte de Norepinefrina
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Radioisótopos do Iodo
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Iodobenzenos
Limite:
Animals
Idioma:
En
Revista:
Synapse
Assunto da revista:
NEUROLOGIA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Reino Unido