Mapping Aldehyde Dehydrogenase 1A1 Activity using an [18F]Substrate-Based Approach

被引:3
作者
Pereira, Raul [1 ,2 ]
Gendron, Thibault [3 ]
Sanghera, Chandan [1 ,2 ]
Greenwood, Hannah E. [1 ,2 ]
Newcombe, Joseph [3 ,4 ]
McCormick, Patrick N. [1 ,2 ]
Sander, Kerstin [3 ]
Topf, Maya [4 ]
Arstad, Erik [3 ]
Witney, Timothy H. [1 ,2 ]
机构
[1] UCL, Ctr Adv Biomed Imaging, Paul OGorman Bldg,72 Huntley St, London WC1E 6DD, England
[2] Kings Coll London, St Thomas Hosp, Dept Imaging Chem & Biol, London SE1 7EH, England
[3] UCL, Dept Chem, 20 Gordon St, London WC1H 0AJ, England
[4] Birkbeck Univ London, Dept Biol Sci Birkbeck, Malet St, London WC1E 7HX, England
基金
英国工程与自然科学研究理事会; 英国惠康基金;
关键词
F-18]fluorination; aldehyde dehydrogenase; cancer; radiochemistry; radiolabeling; CANCER STEM-CELLS; MARKER; INACTIVATION; METABOLISM; MECHANISM; SUBSTRATE; ALDH1A1;
D O I
10.1002/chem.201805473
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Aldehyde dehydrogenases (ALDHs) catalyze the oxidation of aldehydes to carboxylic acids. Elevated ALDH expression in human cancers is linked to metastases and poor overall survival. Despite ALDH being a poor prognostic factor, the non-invasive assessment of ALDH activity in vivo has not been possible due to a lack of sensitive and translational imaging agents. Presented in this report are the synthesis and biological evaluation of ALDH1A1-selective chemical probes composed of an aromatic aldehyde derived from N,N-diethylamino benzaldehyde (DEAB) linked to a fluorinated pyridine ring either via an amide or amine linkage. Of the focused library of compounds evaluated, N-ethyl-6-(fluoro)N-(4-formylbenzyl)nicotinamide 4b was found to have excellent affinity and isozyme selectivity for ALDH1A1 in vitro. Following F-18-fluorination,[F-18]4b was taken up by colorectal tumor cells and trapped through the conversion to its F-18-labeled carboxylate product under the action of ALDH. In vivo positron emission tomography revealed high uptake of [F-18]4b in the lungs and liver, with radioactivity cleared through the urinary tract. Oxidation of [F-18]4b, however, was observed in vivo, which may limit the tissue penetration of this first-in-class radiotracer.
引用
收藏
页码:2345 / 2351
页数:7
相关论文
共 37 条
[1]   Mechanisms of chemoresistance in cancer stem cells [J].
Abdullah, Lissa Nurrul ;
Chow, Edward Kai-Hua .
CLINICAL AND TRANSLATIONAL MEDICINE, 2013, 2
[2]  
AMBROZIAK W, 1991, J BIOL CHEM, V266, P13011
[3]   Surveillance of Cancer Stem Cell Plasticity Using an Isoform-Selective Fluorescent Probe for Aldehyde Dehydrogenase 1A1 [J].
Anorma, Chelsea ;
Hedhli, Jamila ;
Bearrood, Thomas E. ;
Pino, Nicholas W. ;
Gardner, Sarah H. ;
Inaba, Hiroshi ;
Zhang, Pamela ;
Li, Yanfen ;
Feng, Daven ;
Dibrell, Sara E. ;
Kilian, Kristopher A. ;
Dobrucki, Lawrence W. ;
Fan, Timothy M. ;
Chan, Jefferson .
ACS CENTRAL SCIENCE, 2018, 4 (08) :1045-1055
[4]   Human aldehyde dehydrogenase genes: alternatively spliced transcriptional variants and their suggested nomenclature [J].
Black, William J. ;
Stagos, Dimitrios ;
Marchitti, Satori A. ;
Nebert, Daniel W. ;
Tipton, Keith F. ;
Bairoch, Amos ;
Vasiliou, Vasilis .
PHARMACOGENETICS AND GENOMICS, 2009, 19 (11) :893-902
[5]   EVIDENCE THAT THE SLOW CONFORMATION CHANGE CONTROLLING NADH RELEASE FROM THE ENZYME IS RATE-LIMITING DURING THE OXIDATION OF PROPIONALDEHYDE BY ALDEHYDE DEHYDROGENASE [J].
BLACKWELL, LF ;
MOTION, RL ;
MACGIBBON, AKH ;
HARDMAN, MJ ;
BUCKLEY, PD .
BIOCHEMICAL JOURNAL, 1987, 242 (03) :803-808
[6]   Improved purification of hematopoietic stem cells based on their elevated aldehyde dehydrogenase activity [J].
Christ, Oliver ;
Lucke, Kai ;
Imren, Suzan ;
Leung, Karen ;
Hamilton, Melisa ;
Eaves, Allen ;
Smith, Clay ;
Eaves, Connie .
HAEMATOLOGICA, 2007, 92 (09) :1165-1172
[7]   Cytosolic retinoid dehydrogenases govern ubiquitous metabolism of retinol to retinaldehyde followed by tissue-specific metabolism to retinoic acid [J].
Duester, G ;
Mic, FA ;
Molotkov, A .
CHEMICO-BIOLOGICAL INTERACTIONS, 2003, 143 :201-210
[8]   Mechanisms involved in the protection of UV-induced protein inactivation by the corneal crystallin ALDH3A1 [J].
Estey, Tia ;
Cantore, Miriam ;
Weston, Philip A. ;
Carpenter, John F. ;
Petrash, J. Mark ;
Vasiliou, Vasilis .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2007, 282 (07) :4382-4392
[9]   THE HEPATOCELLULAR METABOLISM OF 4-HYDROXYNONENAL BY ALCOHOL-DEHYDROGENASE, ALDEHYDE DEHYDROGENASE, AND GLUTATHIONE-S-TRANSFERASE [J].
HARTLEY, DP ;
RUTH, JA ;
PETERSEN, DR .
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 1995, 316 (01) :197-205
[10]   ALDH-positive lung cancer stem cells confer resistance to epidermal growth factor receptor tyrosine kinase inhibitors [J].
Huang, Cheng-Po ;
Tsai, Meng-Feng ;
Chang, Tzu-Hua ;
Tang, Wei-Chien ;
Chen, Su-Yu ;
Lai, Hsiao-Hsuan ;
Lin, Ting-Yu ;
Yang, James Chih-Hsin ;
Yang, Pan-Chyr ;
Shih, Jin-Yuan ;
Lin, Shwu-Bin .
CANCER LETTERS, 2013, 328 (01) :144-151