A New Positron Emission Tomography (PET) Radioligand for Imaging Sigma-1 Receptors in Living Subjects

Michelle L James; Bin Shen; Cristina L Zavaleta; Carsten Haagen Nielsen; Christophe Mésangeau; Pradeep K Vuppala; Carmel Chan; Bonnie A Avery; James A Fishback; Rae R Matsumoto; Sanjiv S Gambhir; Christopher R McCurdy; Frederick T Chin

doi:10.1021/jm300371c

A New Positron Emission Tomography (PET) Radioligand for Imaging Sigma-1 Receptors in Living Subjects

Michelle L James, Bin Shen, Cristina L Zavaleta, Carsten Haagen Nielsen, Christophe Mésangeau, Pradeep K Vuppala, Carmel Chan, Bonnie A Avery, James A Fishback, Rae R Matsumoto, Sanjiv S Gambhir, Christopher R McCurdy, Frederick T Chin

Department of Biomedical Sciences

56 Citations (Scopus)

Abstract

σ-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 ([¹⁸F]FTC-146, [ ¹⁸F]13). [¹⁸F]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 [¹⁸F]13 in mice showed high uptake of the radioligand in S1R rich regions of the brain. Pretreatment with 1 mg/kg haloperidol (2), nonradioactive 13, or BD1047 (18) reduced the binding of [¹⁸F]13 in the brain at 60 min by 80%, 82%, and 81%, respectively, suggesting that [ ¹⁸F]13 accumulation in mouse brain represents specific binding to S1Rs. These results indicate that [¹⁸F]13 is a promising candidate radiotracer for further evaluation as a tool for studying S1Rs in living subjects.

Original language	English
Journal	Journal of Medicinal Chemistry
Volume	55
Issue number	19
Pages (from-to)	8272-8282
Number of pages	11
ISSN	0022-2623
DOIs	https://doi.org/10.1021/jm300371c
Publication status	Published - 11 Oct 2012

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James, M. L., Shen, B., Zavaleta, C. L., Nielsen, C. H., Mésangeau, C., Vuppala, P. K., Chan, C., Avery, B. A., Fishback, J. A., Matsumoto, R. R., Gambhir, S. S., McCurdy, C. R., & Chin, F. T. (2012). A New Positron Emission Tomography (PET) Radioligand for Imaging Sigma-1 Receptors in Living Subjects. Journal of Medicinal Chemistry, 55(19), 8272-8282. https://doi.org/10.1021/jm300371c

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title = "A New Positron Emission Tomography (PET) Radioligand for Imaging Sigma-1 Receptors in Living Subjects",

abstract = "σ-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 ([18F]FTC-146, [ 18F]13). [18F]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 [18F]13 in mice showed high uptake of the radioligand in S1R rich regions of the brain. Pretreatment with 1 mg/kg haloperidol (2), nonradioactive 13, or BD1047 (18) reduced the binding of [18F]13 in the brain at 60 min by 80%, 82%, and 81%, respectively, suggesting that [ 18F]13 accumulation in mouse brain represents specific binding to S1Rs. These results indicate that [18F]13 is a promising candidate radiotracer for further evaluation as a tool for studying S1Rs in living subjects.",

author = "James, {Michelle L} and Bin Shen and Zavaleta, {Cristina L} and Nielsen, {Carsten Haagen} and Christophe M{\'e}sangeau and Vuppala, {Pradeep K} and Carmel Chan and Avery, {Bonnie A} and Fishback, {James A} and Matsumoto, {Rae R} and Gambhir, {Sanjiv S} and McCurdy, {Christopher R} and Chin, {Frederick T}",

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doi = "10.1021/jm300371c",

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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 - 2012/10/11

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N2 - σ-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 ([18F]FTC-146, [ 18F]13). [18F]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 [18F]13 in mice showed high uptake of the radioligand in S1R rich regions of the brain. Pretreatment with 1 mg/kg haloperidol (2), nonradioactive 13, or BD1047 (18) reduced the binding of [18F]13 in the brain at 60 min by 80%, 82%, and 81%, respectively, suggesting that [ 18F]13 accumulation in mouse brain represents specific binding to S1Rs. These results indicate that [18F]13 is a promising candidate radiotracer for further evaluation as a tool for studying S1Rs in living subjects.

AB - σ-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 ([18F]FTC-146, [ 18F]13). [18F]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 [18F]13 in mice showed high uptake of the radioligand in S1R rich regions of the brain. Pretreatment with 1 mg/kg haloperidol (2), nonradioactive 13, or BD1047 (18) reduced the binding of [18F]13 in the brain at 60 min by 80%, 82%, and 81%, respectively, suggesting that [ 18F]13 accumulation in mouse brain represents specific binding to S1Rs. These results indicate that [18F]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

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SN - 0022-2623

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JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

IS - 19

ER -

A New Positron Emission Tomography (PET) Radioligand for Imaging Sigma-1 Receptors in Living Subjects

Abstract

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