A New Positron Emission Tomography (PET) Radioligand for Imaging Sigma-1 Receptors in Living Subjects
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A New Positron Emission Tomography (PET) Radioligand for Imaging Sigma-1 Receptors in Living Subjects. / James, Michelle L; Shen, Bin; Zavaleta, Cristina L; Nielsen, Carsten Haagen; Mésangeau, Christophe; Vuppala, Pradeep K; Chan, Carmel; Avery, Bonnie A; Fishback, James A; Matsumoto, Rae R; Gambhir, Sanjiv S; McCurdy, Christopher R; Chin, Frederick T.
In: Journal of Medicinal Chemistry, Vol. 55, No. 19, 2012, p. 8272-8282.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - A New Positron Emission Tomography (PET) Radioligand for Imaging Sigma-1 Receptors in Living Subjects
AU - James, Michelle L
AU - Shen, Bin
AU - Zavaleta, Cristina L
AU - Nielsen, Carsten Haagen
AU - Mésangeau, Christophe
AU - Vuppala, Pradeep K
AU - Chan, Carmel
AU - Avery, Bonnie A
AU - Fishback, James A
AU - Matsumoto, Rae R
AU - Gambhir, Sanjiv S
AU - McCurdy, Christopher R
AU - Chin, Frederick T
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
U2 - 10.1021/jm300371c
DO - 10.1021/jm300371c
M3 - Journal article
C2 - 22853801
VL - 55
SP - 8272
EP - 8282
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 19
ER -
ID: 40245966