A New Positron Emission Tomography (PET) Radioligand for Imaging Sigma-1 Receptors in Living Subjects
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Sigma-1 receptor (S1R) radioligands have the potential to detect and monitor various neurological diseases. Herein we report the synthesis, radiofluorination and evaluation of a new S1R ligand 6-(3-fluoropropyl)-3-(2-(azepan-1-yl)ethyl)benzo[d]thiazol-2(3H)-one ([(18)F]FTC-146, [(18)F]13). [(18)F]13 was synthesized by nucleophilic fluorination, affording a product with >99% radiochemical purity (RCP) and specific activity (SA) of 2.6 ± 1.2 Ci/µmol (n = 13) at end of synthesis (EOS). Positron emission tomography (PET) and ex vivo autoradiography studies of [(18)F]13 in mice showed high uptake of the radioligand in S1R rich regions of the brain. Pre-treatment with 1 mg/kg haloperidol (2), non-radioactive 13, or BD1047 (18) reduced the binding of [(18)F]13 in the brain at 60 min by 80%, 82% and 81% respectively, suggesting that [(18)F]13 accumulation in mouse brain represents specific binding to S1Rs. These results indicate that [(18)F]13 is a promising candidate radiotracer for further evaluation as a tool for studying S1Rs in living subjects.
Originalsprog | Engelsk |
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Tidsskrift | Journal of Medicinal Chemistry |
Vol/bind | 55 |
Udgave nummer | 19 |
Sider (fra-til) | 8272-8282 |
Antal sider | 11 |
ISSN | 0022-2623 |
DOI | |
Status | Udgivet - 2012 |
ID: 40245966