Design, radiosynthesis, and evaluation of radiotracers for positron emission tomography imaging of stearoyl-CoA desaturase-1

William C. Silvers; Hancheng Cai; Orhan K. Öz; Xiankai Sun

doi:10.1016/j.bmcl.2015.12.062

Design, radiosynthesis, and evaluation of radiotracers for positron emission tomography imaging of stearoyl-CoA desaturase-1

William C. Silvers, Hancheng Cai, Orhan K. Öz, Xiankai Sun

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Design, radiosynthesis, and biological evaluation of two radiotracers (N-(3-[¹⁸F]fluoropropyl)-6-(4-(trifluoromethyl)benzoyl)-piperazin-1-yl)pyridazine-3-carboxamide (¹⁸F-FPPPT) and (N-(4-[¹⁸F]fluoroaniline)-6-(4-(trifluoromethyl)benzoyl)-piperazin-1-yl)pyridazine-3-carboxamide (¹⁸F-FAPPT)) are described for noninvasive assessment of stearoyl-CoA desaturase-1 (SCD-1). The overexpression of SCD-1 in multiple solid tumors associates with poor survival in cancer patients. The two radiotracers,¹⁸F-FPPPT and¹⁸F-FAPPT, were each prepared in three steps in radiochemical yields of 21% and 3%, respectively. The practicality of imaging SCD-1 with¹⁸F-FPPPT was tested in two mouse models bearing xenograft tumors with different levels of SCD-1 expression, which afforded a 1.8-fold uptake difference correspondingly. Our work indicates that it is possible to develop SCD-1 specific imaging probes from previously reported SCD-1 inhibitors.

Original language	English (US)
Pages (from-to)	924-927
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	26
Issue number	3
DOIs	https://doi.org/10.1016/j.bmcl.2015.12.062
State	Published - 2016

Keywords

De novo lipid metabolism
F-FPPPT
PET
Radiosynthesis
Stearoyl-CoA desaturase

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmcl.2015.12.062

Cite this

@article{7716d7a2da5c41e8bf8a8f9d4d146dd8,

title = "Design, radiosynthesis, and evaluation of radiotracers for positron emission tomography imaging of stearoyl-CoA desaturase-1",

abstract = "Design, radiosynthesis, and biological evaluation of two radiotracers (N-(3-[18F]fluoropropyl)-6-(4-(trifluoromethyl)benzoyl)-piperazin-1-yl)pyridazine-3-carboxamide (18F-FPPPT) and (N-(4-[18F]fluoroaniline)-6-(4-(trifluoromethyl)benzoyl)-piperazin-1-yl)pyridazine-3-carboxamide (18F-FAPPT)) are described for noninvasive assessment of stearoyl-CoA desaturase-1 (SCD-1). The overexpression of SCD-1 in multiple solid tumors associates with poor survival in cancer patients. The two radiotracers,18F-FPPPT and18F-FAPPT, were each prepared in three steps in radiochemical yields of 21% and 3%, respectively. The practicality of imaging SCD-1 with18F-FPPPT was tested in two mouse models bearing xenograft tumors with different levels of SCD-1 expression, which afforded a 1.8-fold uptake difference correspondingly. Our work indicates that it is possible to develop SCD-1 specific imaging probes from previously reported SCD-1 inhibitors.",

keywords = "De novo lipid metabolism, F-FPPPT, PET, Radiosynthesis, Stearoyl-CoA desaturase",

author = "Silvers, {William C.} and Hancheng Cai and {\"O}z, {Orhan K.} and Xiankai Sun",

note = "Funding Information: This study was partially supported by a grant from the National Institutes of Health ( R01 DK092163 ) and the Dr. Jack Krohmer Professorship Funds. The Professorship Funds is an endowment provided to the corresponding author by University of Texas Southwestern Medical Center. Publisher Copyright: {\textcopyright} 2015 Elsevier Ltd. All rights reserved.",

year = "2016",

doi = "10.1016/j.bmcl.2015.12.062",

language = "English (US)",

volume = "26",

pages = "924--927",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "3",

}

TY - JOUR

T1 - Design, radiosynthesis, and evaluation of radiotracers for positron emission tomography imaging of stearoyl-CoA desaturase-1

AU - Silvers, William C.

AU - Cai, Hancheng

AU - Öz, Orhan K.

AU - Sun, Xiankai

N1 - Funding Information: This study was partially supported by a grant from the National Institutes of Health ( R01 DK092163 ) and the Dr. Jack Krohmer Professorship Funds. The Professorship Funds is an endowment provided to the corresponding author by University of Texas Southwestern Medical Center. Publisher Copyright: © 2015 Elsevier Ltd. All rights reserved.

PY - 2016

Y1 - 2016

N2 - Design, radiosynthesis, and biological evaluation of two radiotracers (N-(3-[18F]fluoropropyl)-6-(4-(trifluoromethyl)benzoyl)-piperazin-1-yl)pyridazine-3-carboxamide (18F-FPPPT) and (N-(4-[18F]fluoroaniline)-6-(4-(trifluoromethyl)benzoyl)-piperazin-1-yl)pyridazine-3-carboxamide (18F-FAPPT)) are described for noninvasive assessment of stearoyl-CoA desaturase-1 (SCD-1). The overexpression of SCD-1 in multiple solid tumors associates with poor survival in cancer patients. The two radiotracers,18F-FPPPT and18F-FAPPT, were each prepared in three steps in radiochemical yields of 21% and 3%, respectively. The practicality of imaging SCD-1 with18F-FPPPT was tested in two mouse models bearing xenograft tumors with different levels of SCD-1 expression, which afforded a 1.8-fold uptake difference correspondingly. Our work indicates that it is possible to develop SCD-1 specific imaging probes from previously reported SCD-1 inhibitors.

AB - Design, radiosynthesis, and biological evaluation of two radiotracers (N-(3-[18F]fluoropropyl)-6-(4-(trifluoromethyl)benzoyl)-piperazin-1-yl)pyridazine-3-carboxamide (18F-FPPPT) and (N-(4-[18F]fluoroaniline)-6-(4-(trifluoromethyl)benzoyl)-piperazin-1-yl)pyridazine-3-carboxamide (18F-FAPPT)) are described for noninvasive assessment of stearoyl-CoA desaturase-1 (SCD-1). The overexpression of SCD-1 in multiple solid tumors associates with poor survival in cancer patients. The two radiotracers,18F-FPPPT and18F-FAPPT, were each prepared in three steps in radiochemical yields of 21% and 3%, respectively. The practicality of imaging SCD-1 with18F-FPPPT was tested in two mouse models bearing xenograft tumors with different levels of SCD-1 expression, which afforded a 1.8-fold uptake difference correspondingly. Our work indicates that it is possible to develop SCD-1 specific imaging probes from previously reported SCD-1 inhibitors.

KW - De novo lipid metabolism

KW - F-FPPPT

KW - PET

KW - Radiosynthesis

KW - Stearoyl-CoA desaturase

UR - http://www.scopus.com/inward/record.url?scp=84979161104&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84979161104&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2015.12.062

DO - 10.1016/j.bmcl.2015.12.062

M3 - Article

C2 - 26778147

AN - SCOPUS:84979161104

SN - 0960-894X

VL - 26

SP - 924

EP - 927

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 3

ER -

Design, radiosynthesis, and evaluation of radiotracers for positron emission tomography imaging of stearoyl-CoA desaturase-1

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this