Synthesis and initial evaluation of radioiodine-labelled deuterated tropane derivatives targeting dopamine transporter.
Bioorg Med Chem Lett
; 102: 129678, 2024 Apr 01.
Article
em En
| MEDLINE
| ID: mdl-38408514
ABSTRACT
The dopamine transporter (DAT) is closely related to a variety of neurological disorders including Parkinson's disease (PD) and other neurodegenerative diseases. In vivo imaging of DAT with radio-labelled tracers has become a powerful technique in related disorders. The radioiodine-labelled tropane derivative [123I]FP-CIT ([123I]1a) is widely used in clinical single photon emission computed tomography (SPECT) imaging as a DAT imaging agent. To develop more metabolically stable DAT radioligands for accurate imaging, this work compared two novel deuterated tropane derivatives ([131I]1c-d) with non-deuterated tropane derivatives ([131I]1a-b). [131I]1a-d were obtained in high radiochemical purity (RCP) above 99 % with molar activities of 7.0-10.0 GBq/µmol. The [131I]1a and [131I]1c exhibited relatively higher affinity to DAT (Ki 2.0-3.12 nM) than [131I]1b and [131I]1d. Biodistribution results showed that [131I]1c consistently exhibited a higher ratio of the target to non-target (striatum/cerebellum) than [131I]1a. Furthermore, metabolism studies indicated that the in vivo metabolic stability of [131I]1c was superior to that of [131I]1a. Ex vivo autoradiography showed that [131I]1c selectively localized on DAT-rich striatal regions and the specific signal could be blocked by DAT inhibitor. These results indicated that [131I]1c might be a potential probe for DAT SPECT imaging in the brain.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas da Membrana Plasmática de Transporte de Dopamina
/
Radioisótopos do Iodo
Idioma:
En
Revista:
Bioorg Med Chem Lett
Assunto da revista:
BIOQUIMICA
/
QUIMICA
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China