In Vivo Chemiluminescent Imaging Agents for Nitroreductase and Tissue Oxygenation

被引：104

作者：

Cao, Jian ^{[1
,2
]}

Campbell, James ^{[4
]}

Liu, Li ^{[4
]}

Mason, Ralph P. ^{[4
]}

Lippert, Alexander R. ^{[1
,2
,3
]}

机构：

[1] Southern Methodist Univ, Dept Chem, Dallas, TX 75275 USA

[2] Southern Methodist Univ, Ctr Drug Discovery Design & Delivery CD4, Dallas, TX 75275 USA

[3] Southern Methodist Univ, CGHI, Dallas, TX 75275 USA

[4] UT Southwestern Med Ctr, Dept Radiol, Preclin Imaging Sect, PIRL, Dallas, TX 75390 USA

来源：

ANALYTICAL CHEMISTRY | 2016年 / 88卷 / 09期

基金：

美国国家卫生研究院;

关键词：

ESCHERICHIA-COLI; FLUORESCENT-PROBES; HYPOXIA; TUMOR; CANCER; CONTRAST; BOLD; 1,2-DIOXETANES; PIMONIDAZOLE; DERIVATIVES;

D O I：

10.1021/acs.analchem.6b01096

中图分类号：

O65 [分析化学];

学科分类号：

070302 ; 081704 ;

摘要：

Tissue oxygenation is a driving parameter of the tumor microenvironment, and hypoxia can be a prognostic indicator of aggressiveness, metastasis, and poor response to therapy. Here, we report a chemiluminescence imaging (CLI) agent based on the oxygen-dependent reduction of a nitroaromatic spiroadamantane 1,2-dioxetane scaffold. Hypoxia ChemiLuminescent Probe 2 (HyCL-2) responds to nitroreductase with similar to 170-fold increase in luminescence intensity and high selectivity for enzymatic reductase versus other small molecule reductants. HyCL-2 can image exogenous nitroreductase in vitro and in vivo in living mice, and total luminescent intensity is increased by similar to 6-fold under low oxygen conditions. H-yCL-2 is demonstrated to report on tumor oxygenation during an oxygen challenge in H1299 lung tumor xenografts grown in a murine model as independently confirmed using multispectral optoacoustic tomography (MSOT) imaging of hemoglobin oxygenation.

引用

页码：4995 / 5002

页数：8

共 80 条

[1] Efficiency of Electron Transfer Initiated Chemiluminescence [J].

Augusto, Felipe A. ;

de Souza, Glalci A. ;

de Souza Junior, Sergio P. ;

Khalid, Muhammad ;

Baader, Wilhelm J. .

PHOTOCHEMISTRY AND PHOTOBIOLOGY, 2013, 89 (06) :1299-1317

[2] Nitroreductase-triggered activation of a novel caged fluorescent probe obtained from methylene blue [J].

Bae, Jungeun ;

McNamara, Louis E. ;

Nael, Manal A. ;

Mahdi, Fakhri ;

Doerksen, Robert J. ;

Bidwell, Gene L., III ;

Hammer, Nathan I. ;

Jo, Seongbong .

CHEMICAL COMMUNICATIONS, 2015, 51 (64) :12787-12790

[3] A BODIPY-luminol chemiluminescent resonance energy-transfer (CRET) cassette for imaging of cellular superoxide [J].

Bag, S. ;

Tseng, J. -C. ;

Rochford, J. .

ORGANIC & BIOMOLECULAR CHEMISTRY, 2015, 13 (06) :1763-1767

[4]

Baumes JM, 2010, NAT CHEM, V2, P1025, DOI [10.1038/nchem.871, 10.1038/NCHEM.871]

[5] O2-Sensitive MRI Distinguishes Brain Tumor Versus Radiation Necrosis in Murine Models [J].

Beeman, Scott C. ;

Shui, Ying-Bo ;

Perez-Torres, Carlos J. ;

Engelbach, John A. ;

Ackerman, Joseph J. H. ;

Garbow, Joel R. .

MAGNETIC RESONANCE IN MEDICINE, 2016, 75 (06) :2442-2447

[6]

Bronstein I. Y., 1996, U. S. Patent, Patent No. [5,538,847, 5538847]

[7] Exploiting tumour hypoxia in cancer treatment [J].

Brown, JM ;

William, WR .

NATURE REVIEWS CANCER, 2004, 4 (06) :437-447

[8]

BRYANT C, 1991, J BIOL CHEM, V266, P4119

[9] TYPE-I NITROREDUCTASES OF ESCHERICHIA-COLI [J].

BRYANT, DW ;

MCCALLA, DR ;

LEEKSMA, M ;

LANEUVILLE, P .

CANADIAN JOURNAL OF MICROBIOLOGY, 1981, 27 (01) :81-86

[10] Chemiluminescent probes for imaging H2S in living animals [J].

Cao, J. ;

Lopez, R. ;

Thacker, J. M. ;

Moon, J. Y. ;

Jiang, C. ;

Morris, S. N. S. ;

Bauer, J. H. ;

Tao, P. ;

Mason, R. P. ;

Lippert, A. R. .

CHEMICAL SCIENCE, 2015, 6 (03) :1979-1985

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