Novel 7α-alkoxy-17α-(4′-halophenylethynyl)estradiols as potential SPECT/PET imaging agents for estrogen receptor expressing tumours: Synthesis and binding affinity evaluation

被引：16

作者：

Neto, Carina ^{[1
]}

Oliveira, Maria Cristina ^{[1
]}

Gano, Lurdes ^{[1
]}

Marques, Fernanda ^{[1
]}

Yasuda, Takumi ^{[2
,3
]}

Thiemann, Thies ^{[2
,3
]}

Kniess, Torsten ^{[4
]}

Santos, Isabel ^{[1
]}

机构：

[1] Univ Tecn Lisboa, Unidade Ciencias Quim & Radiofarmaceut, Inst Tecnol & Nucl, Inst Super Tecn, P-2686953 Sacavem, Portugal

[2] Kyushu Univ, Interdisciplinary Grad Sch Engn Sci, Kasuga, Fukuoka 8168580, Japan

[3] United Arab Emirates Univ, Dept Chem, Fac Sci, Al Ain, U Arab Emirates

[4] Helmholtz Zentrum Dresden Rossendorf eV, Inst Radiopharm, D-01314 Dresden, Germany

来源：

STEROIDS | 2012年 / 77卷 / 11期

关键词：

Breast cancer; Estrogen receptor (ER); Estradiol; Positron emission tomography (PET); Single photon emission computerized tomography (SPECT); Imaging; POSITRON-EMISSION-TOMOGRAPHY; CROSS-COUPLING REACTIONS; HUMAN-BREAST-CANCER; ESTRADIOL DERIVATIVES; FLUORINE-18-LABELED ESTROGENS; IMMATURE RATS; THERAPY; BETA; BIODISTRIBUTION; RADIOLIGAND;

D O I：

10.1016/j.steroids.2012.05.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In order to develop potential radiolabelled probes for imaging estrogen receptor (ER) positive tumours, we have synthesized and characterized a series of novel 7 alpha-alkoxy-17 alpha-(4'-iodophenylethynyl)estra-1,3,5(10)-triene-3,17 beta-diols and 7 alpha-alkoxy-17 alpha-(4'-fluorophenylethynyl)estra-1,3,5(10)-triene-3,17 beta-diols. The fluoro-substituted compounds showed a higher ER binding affinity than the corresponding iodo-derivatives, where 7 alpha-methoxy- and 17 alpha-(4'-fluorophenylethynyl)estra-1,3,5(10)-triene-3,17 beta-diol showed the highest ER binding affinities (RBA = 80.9% and 78.9%, respectively), among the halophenylethynyl compounds studied and should be further explored as potential PET biomarkers for imaging of ER expressing tumours. (C) 2012 Elsevier Inc. All rights reserved.

引用

页码：1123 / 1132

页数：10

共 64 条

[1] Synthesis and biological properties of 7α-cyano derivatives of the (17α,20E/Z)-[125I]iodovinyl- and 16α-[125I]iodo-estradiols [J].

Ali, H ;

Rousseau, J ;

Paquette, B ;

Dubé, C ;

Marko, B ;

van Lier, JE .

STEROIDS, 2003, 68 (14) :1189-1200

[2] Synthesis of 17-α-substituted estradiol-pyridin-2-yl hydrazine conjugates as effective ligands for labeling with Alberto's complex fac-[Re(OH2)3(CO)3]+ in water [J].

Arterburn, JB ;

Corona, C ;

Rao, KV ;

Carlson, KE ;

Katzenellenbogen, JA .

JOURNAL OF ORGANIC CHEMISTRY, 2003, 68 (18) :7063-7070

[3] An estradiol-conjugate for radiolabelling with 177Lu:: an attempt to prepare a radiotherapeutic agent [J].

Banerjee, S ;

Das, T ;

Chakraborty, S ;

Samuel, G ;

Korde, A ;

Venkatesh, M ;

Pillai, MRA .

BIOORGANIC & MEDICINAL CHEMISTRY, 2005, 13 (13) :4315-4322

[4] Assessment of Human Biodistribution and Dosimetry of 4-Fluoro-11β-Methoxy-16α-18F-Fluoroestradiol Using Serial Whole-Body PET/CT [J].

Beauregard, Jean-Mathieu ;

Croteau, Etienne ;

Ahmed, Naseem ;

van Lier, Johan E. ;

Benard, Francois .

JOURNAL OF NUCLEAR MEDICINE, 2009, 50 (01) :100-107

[5] Imaging in breast cancer:: Single-photon computed tomography and positron-emission tomography [J].

Bénard, F ;

Turcotte, É .

BREAST CANCER RESEARCH, 2005, 7 (04) :153-162

[6] [18F]fluorinated estradiol derivatives for oestrogen receptor imaging:: impact of substituents, formulation and specific activity on the biodistribution in breast tumour-bearing mice [J].

Benard, Francois ;

Ahmed, Naseem ;

Beauregard, Jean-Mathieu ;

Rousseau, Jacques ;

Aliaga, Antonio ;

Dubuc, Celena ;

Croteau, Etienne ;

van Lier, Johan E. .

EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 2008, 35 (08) :1473-1479

[7] Estrogen receptor status in primary breast cancer:: Iodine 123-labeled cis-11β-methoxy-17α-iodovinyl estradiol scintigraphy [J].

Bennink, RJ ;

Rijks, LJ ;

van Tienhoven, G ;

Noorduyn, LA ;

Janssen, AG ;

Sloof, GW .

RADIOLOGY, 2001, 220 (03) :774-779

[8]

Berube M.KamalF, 2006, SYNTHESIS-STUTTGART, V2006, P91

[9] SYNTHESIS, RESOLUTION AND RACEMIZATION STUDIES OF 1,2-EPOXY-1,2-DIHYDROCHRYSENE [J].

BOYD, DR ;

GREENE, RME .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1982, (07) :1535-1539

[10] Estrogen receptor subtypes in ovarian cancer - A clinical correlation [J].

Chan, Karen K. L. ;

Wei, Na ;

Liu, Stephanie S. ;

Xiao-Yun, Liao ;

Cheung, Annie N. ;

Ngan, Hextan Y. S. .

OBSTETRICS AND GYNECOLOGY, 2008, 111 (01) :144-151

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