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

被引：83

作者：

James, Michelle L. ^{[1
]}

Shen, Bin ^{[1
]}

Zavaleta, Cristina L. ^{[1
]}

Nielsen, Carsten H. ^{[1
,2
]}

Mesangeau, Christophe ^{[4
]}

Vuppala, Pradeep K. ^{[3
]}

Chan, Carmel ^{[1
]}

Avery, Bonnie A. ^{[3
]}

Fishback, James A. ^{[5
]}

Matsumoto, Rae R. ^{[5
]}

Gambhir, Sanjiv S. ^{[1
]}

McCurdy, Christopher R. ^{[4
]}

Chin, Frederick T. ^{[1
]}

机构：

[1] Stanford Univ, Dept Radiol, Mol Imaging Program Stanford, Stanford, CA 94305 USA

[2] Univ Copenhagen, Rigshospitalet, Dept Clin Physiol Nucl Med & PET, DK-2100 Copenhagen, Denmark

[3] Univ Mississippi, Dept Pharmaceut, University, MS 38677 USA

[4] Univ Mississippi, Dept Med Chem, University, MS 38677 USA

[5] W Virginia Univ, Sch Pharm, Dept Basic Pharmaceut Sci, Morgantown, WV 26506 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2012年 / 55卷 / 19期

关键词：

IN-VIVO EVALUATION; HIGHLY POTENT; HUMAN BRAIN; BINDING; DERIVATIVES; SA4503; LIGAND; COCAINE; AFFINITIES; ANTAGONIST;

D O I：

10.1021/jm300371c

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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 ([F-18]FTC-146, [F-18]13). [F-18]13 was synthesized by nucleophilic fluorination, affording a product with >99% radiochemical purity (RCP) and specific activity (SA) of 2.6 +/- 1.2 Ci/mu mol (n = 13) at end of synthesis (EOS). Positron emission tomography (PET) and ex vivo autoradiography studies of [F-18]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 [F-18]13 in the brain at 60 min by 80%, 82%, and 81%, respectively, suggesting that [F-18]13 accumulation in mouse brain represents specific binding to S1Rs. These results indicate that [F-18]13 is a promising candidate radiotracer for further evaluation as a tool for studying S1Rs in living subjects.

引用

页码：8272 / 8282

页数：11

共 57 条

[1] Methyl substitution on the piperidine ring of N-[ω-(6-methoxynaphthalen-1-yl)alkyl] derivatives as a probe for selective binding and activity at the σ1 receptor [J].

Berardi, F ;

Ferorelli, S ;

Abate, C ;

Pedone, MP ;

Colabufo, NA ;

Contino, M ;

Perrone, R .

JOURNAL OF MEDICINAL CHEMISTRY, 2005, 48 (26) :8237-8244

[2] A multireceptorial binding reinvestigation on an extended class of σ ligands:: N-[ω-(Indan-1-yl and tetralin-1-yl)alkyl] derivatives of 3,3-dimethylpiperidine reveal high affinities towards σ1 and EBP sites [J].

Berardi, F ;

Ferorelli, S ;

Colabufo, NA ;

Leopoldo, M ;

Perrone, R ;

Tortorella, V .

BIOORGANIC & MEDICINAL CHEMISTRY, 2001, 9 (05) :1325-1335

[3]

Collier TL, 2007, CURR PHARM DESIGN, V13, P51

[4] Methods for determining n-octanol-water partition constants [J].

Danielsson, LG ;

Zhang, YH .

TRAC-TRENDS IN ANALYTICAL CHEMISTRY, 1996, 15 (04) :188-196

[5] Molecular imaging of σ receptors: synthesis and evaluation of the potent σ1 selective radioligand [18F]fluspidine [J].

Fischer, Steffen ;

Wiese, Christian ;

Maestrup, Eva Grosse ;

Hiller, Achim ;

Deuther-Conrad, Winnie ;

Scheunemann, Matthias ;

Schepmann, Dirk ;

Steinbach, Joerg ;

Wuensch, Bernhard ;

Brust, Peter .

EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 2011, 38 (03) :540-551

[6]

Fishback J. A., 2011, THESIS W VIRGINIA U

[7] Synthesis and characterization of [3H]-SN56, a novel radioligand for the σ1 receptor [J].

Fishback, James A. ;

Mesangeau, Christophe ;

Poupaert, Jacques H. ;

McCurdy, Christopher R. ;

Matsumoto, Rae R. .

EUROPEAN JOURNAL OF PHARMACOLOGY, 2011, 653 (1-3) :1-7

[8] Release of [H-3]dopamine from guinea pig striatal slices is modulated by sigma(1) receptor agonists [J].

Gonzalez, GM ;

Werling, LL .

NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 1997, 356 (04) :455-461

[9] Sigma receptors: biology and therapeutic potential [J].

Guitart, X ;

Codony, X ;

Monroy, X .

PSYCHOPHARMACOLOGY, 2004, 174 (03) :301-319

[10] σ1-receptor ligand 4-phenyl-1-(4-phenylbutyl)-piperidine affords neuroprotection from focal ischemia with prolonged reperfusion [J].

Harukuni, I ;

Bhardwaj, A ;

Shaivitz, AB ;

DeVries, AC ;

London, ED ;

Hurn, PD ;

Traystman, RJ ;

Kirsch, JR .

STROKE, 2000, 31 (04) :976-981

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