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Article ; Online: Imaging cycling tumor hypoxia.

Matsumoto, Shingo / Yasui, Hironobu / Mitchell, James B / Krishna, Murali C

2010 Volume 70, Issue 24, Page(s) 10019–10023

Abstract: ... to radiation and chemotherapy. Imaging of cycling hypoxia in tumors can provide capabilities to help plan ... Cycling hypoxia is now a well-recognized phenomenon in animal and human solid tumors. Cycling ... in erythrocyte flux, perfusion, and also development of newer vascular networks. Cycling hypoxia has been shown ...

Abstract	Cycling hypoxia is now a well-recognized phenomenon in animal and human solid tumors. Cycling hypoxia can exist more than 100-μm distances from a microvessel, and some of these regions have been shown to exist adjacent to normal tissue. Fluctuations in pO(2) of approximately 20 mm Hg can occur with periodicities of minutes to hours and even days. These fluctuations have been attributed to changes in erythrocyte flux, perfusion, and also development of newer vascular networks. Cycling hypoxia has been shown to induce the expression of hypoxia-inducible transcription factor-1α (HIF-1α) and also confer tumor cells and tumor vascular endothelial cells with enhanced prosurvival pathways, making tumors less responsive to radiation and chemotherapy. Imaging of cycling hypoxia in tumors can provide capabilities to help plan appropriate treatment, by taking into account the magnitude and frequency of fluctuations and also their locations adjacent to normal tissue. Electron paramagnetic resonance imaging (EPRI) provides the ability to distinguish chronic and cycling hypoxic regions and has the required spatial and temporal resolutions to provide quantitative maps of tumor pO(2). EPRI can serve as a valuable tool in examining tumor pO(2) longitudinally in response to treatment and in an experimentally chosen time window to spatially map fluctuations in pO(2) noninvasively in animal models of implanted or orthotopic tumors, with a potential for human applications.
MeSH term(s)	Animals ; Cell Hypoxia/physiology ; Electron Spin Resonance Spectroscopy/methods ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Neoplasms/metabolism ; Neoplasms/pathology ; Oxygen/metabolism ; Partial Pressure
Chemical Substances	Hypoxia-Inducible Factor 1, alpha Subunit ; Oxygen (S88TT14065)
Language	English
Publishing date	2010-12-14
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-10-2821
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Article ; Online: Low-field magnetic resonance imaging to visualize chronic and cycling hypoxia in tumor-bearing mice.

Yasui, Hironobu / Matsumoto, Shingo / Devasahayam, Nallathamby / Munasinghe, Jeeva P / Choudhuri, Rajani / Saito, Keita / Subramanian, Sankaran / Mitchell, James B / Krishna, Murali C

Cancer research

2010 Volume 70, Issue 16, Page(s) 6427–6436

Abstract: ... sensitivity regions, which responded to carbogen, corresponding to cycling hypoxia and chronic hypoxia ... every 3 minutes for a total of 30 minutes in two different tumor types revealed that fluctuation patterns ... in pO(2) are dependent on tumor size and tumor type. The magnitude of fluctuations in pO(2) in SCCVII ...

Abstract	Tumors exhibit fluctuations in blood flow that influence oxygen concentrations and therapeutic resistance. To assist therapeutic planning and improve prognosis, noninvasive dynamic imaging of spatial and temporal variations in oxygen partial pressure (pO(2)) would be useful. Here, we illustrate the use of pulsed electron paramagnetic resonance imaging (EPRI) as a novel imaging method to directly monitor fluctuations in oxygen concentrations in mouse models. A common resonator platform for both EPRI and magnetic resonance imaging (MRI) provided pO(2) maps with anatomic guidance and microvessel density. Oxygen images acquired every 3 minutes for a total of 30 minutes in two different tumor types revealed that fluctuation patterns in pO(2) are dependent on tumor size and tumor type. The magnitude of fluctuations in pO(2) in SCCVII tumors ranged between 2- to 18-fold, whereas the fluctuations in HT29 xenografts were of lower magnitude. Alternating breathing cycles with air or carbogen (95% O(2) plus 5% CO(2)) distinguished higher and lower sensitivity regions, which responded to carbogen, corresponding to cycling hypoxia and chronic hypoxia, respectively. Immunohistochemical analysis suggests that the fluctuation in pO(2) correlated with pericyte density rather than vascular density in the tumor. This EPRI technique, combined with MRI, may offer a powerful clinical tool to noninvasively detect variable oxygenation in tumors.
MeSH term(s)	Adenocarcinoma/blood supply ; Adenocarcinoma/metabolism ; Adenocarcinoma/pathology ; Animals ; Carcinoma, Squamous Cell/blood supply ; Carcinoma, Squamous Cell/metabolism ; Carcinoma, Squamous Cell/pathology ; Cell Hypoxia/physiology ; Colonic Neoplasms/blood supply ; Colonic Neoplasms/metabolism ; Colonic Neoplasms/pathology ; Electron Spin Resonance Spectroscopy/methods ; Female ; HT29 Cells ; Humans ; Immunohistochemistry ; Magnetic Resonance Imaging/methods ; Mice ; Mice, Inbred C3H ; Mice, Nude ; Neoplasm Transplantation ; Oxygen/analysis ; Oxygen/metabolism ; Partial Pressure ; Transplantation, Heterologous
Chemical Substances	Oxygen (S88TT14065)
Language	English
Publishing date	2010-07-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	1432-1
ISSN	1538-7445 ; 0008-5472
ISSN (online)	1538-7445
ISSN	0008-5472
DOI	10.1158/0008-5472.CAN-10-1350
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Article ; Online: Chitosan nanoplatform for the co-delivery of palbociclib and ultra-small magnesium nanoclusters: dual receptor targeting, therapy and imaging.

Mehata, Abhishesh Kumar / Singh, Virendra / Vikas / Srivastava, Prachi / Koch, Biplob / Kumar, Manoj / Muthu, Madaswamy S

Nanotheranostics

2024 Volume 8, Issue 2, Page(s) 179–201

Abstract: ... significantly suppressing tumor vascularity compared to free PB, nontargeted, FR targeted and ER targeted NPs ... demonstrated that dual targeted theranostic NPs were capable of effectively reducing hypoxic tumor volume and ... chitosan nanoparticles were developed for breast cancer imaging and therapy. These nanoparticles (NPs) were ...

Abstract	Theranostic nanoparticles have gained significant attention in cancer diagnosis and therapy. In this study, estrone (ES) and folic acid (FA) functionalized single and dual receptor targeted theranostic chitosan nanoparticles were developed for breast cancer imaging and therapy. These nanoparticles (NPs) were loaded with palbociclib (PB) and ultra-small magnesium nanoclusters (UMN). The developed nontargeted theranostic NPs (PB-UMN-CS-NPs), estrogen receptor targeted theranostic NPs (PB-UMN-CS-ES-NPs), folate receptor targeted theranostic NPs (PB-UMN-CS-FA-NPs), and dual targeted theranostic NPs (PB-UMN-CS-ES-FA-NPs) have particle sizes of 178.4 ± 1.21 nm, 181.6± 1.35 nm, 185.1± 1.33 nm, and 198.2± 1.43 nm with surface charges of +19.02± 0.382 mV, +13.89±0.410 mV, +16.72±0.527 mV and +15.23±0.377 mV, respectively. Cytotoxicity studies on estrogen receptor (ER) and folate receptor (FR) expressing breast cancer cells revealed that dual-targeted theranostic NPs (PB-UMN-CS-FA-ES-NPs) were more effective, inhibiting cell growth by 54.17 and 42.23 times in MCF-7 and T-47D cells compared to free PB, respectively. Additionally, developed NPs were capable of inhibiting the cell cycle progression of MCF-7 cells from the G1 phase to the S phase more efficiently compared to free PB. Ultrasound and photoacoustic (USG/PA) imaging demonstrated that dual targeted theranostic NPs were capable of effectively reducing hypoxic tumor volume and significantly suppressing tumor vascularity compared to free PB, nontargeted, FR targeted and ER targeted NPs. Moreover,
MeSH term(s)	Humans ; Female ; Chitosan ; Magnesium ; Folic Acid ; Breast Neoplasms/diagnostic imaging ; Breast Neoplasms/drug therapy ; Receptors, Estrogen ; Piperazines ; Pyridines
Chemical Substances	palbociclib (G9ZF61LE7G) ; Chitosan (9012-76-4) ; Magnesium (I38ZP9992A) ; Folic Acid (935E97BOY8) ; Receptors, Estrogen ; Piperazines ; Pyridines
Language	English
Publishing date	2024-02-12
Publishing country	Australia
Document type	Journal Article
ISSN	2206-7418
ISSN (online)	2206-7418
DOI	10.7150/ntno.94364
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Article ; Online: Protoporphyrin IX delayed fluorescence imaging: a modality for hypoxia-based surgical guidance.

Pétusseau, Arthur / Bruza, Petr / Pogue, Brian

Journal of biomedical optics

2022 Volume 27, Issue 10

Abstract: ... that most tumors have microregional chronic and/or cycling hypoxia present as well as chaotic blood flow ... we show the first demonstration of imaging hypoxia signals from PpIX in a pancreatic cancer model ... emission in hypoxic tumor tissue regions, which is measured as a DF signal in the red to near-infrared ...

Abstract	SignificanceHypoxia imaging for surgical guidance has never been possible, yet it is well known that most tumors have microregional chronic and/or cycling hypoxia present as well as chaotic blood flow. The ability to image oxygen partial pressure (pO2) is therefore a unique control of tissue metabolism and can be used in a range of disease applications to understand the complex biochemistry of oxygen supply and consumption.AimDelayed fluorescence (DF) from the endogenous molecule protoporphyrin IX (PpIX) has been shown to be a truly unique reporter of the local oxygen partial pressure in tissue. PpIX is endogenously synthesized by mitochondria in most tissues, and the particular property of DF emission is directly related to low microenvironmental oxygen concentration. Here, it is shown that PpIX has a unique emission in hypoxic tumor tissue regions, which is measured as a DF signal in the red to near-infrared spectrum.ApproachA time-gated imaging system was used for PpIX DF for wide field direct mapping of pO2 changes. Acquiring both prompt and DF in a rapid sequential cycle allowed for imaging oxygenation in a way that was insensitive to the PpIX concentration. By choosing adequate parameters, the video rate acquisition of pO2 images could be achieved, providing real-time tissue metabolic information.ResultsIn this report, we show the first demonstration of imaging hypoxia signals from PpIX in a pancreatic cancer model, exhibiting >5X contrast relative to surrounding normal oxygenated tissues. Additionally, tissue palpation amplifies the signal and provides intuitive temporal contrast based upon neoangiogenic blood flow differences.ConclusionsPpIX DF provides a mechanism for tumor contrast that could easily be translated to human use as an intrinsic contrast mechanism for oncologic surgical guidance.
MeSH term(s)	Aminolevulinic Acid/metabolism ; Fluorescence ; Humans ; Hypoxia/diagnostic imaging ; Neoplasms ; Oxygen/metabolism ; Photosensitizing Agents/metabolism ; Protoporphyrins/metabolism
Chemical Substances	Photosensitizing Agents ; Protoporphyrins ; Aminolevulinic Acid (88755TAZ87) ; protoporphyrin IX (C2K325S808) ; Oxygen (S88TT14065)
Language	English
Publishing date	2022-10-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1309154-2
ISSN	1560-2281 ; 1083-3668
ISSN (online)	1560-2281
ISSN	1083-3668
DOI	10.1117/1.JBO.27.10.106005
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Zs.A 4699: Show issues

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Article ; Online: Application of Magnetic Resonance Imaging in Neoadjuvant Treatment of Pancreatic Ductal Adenocarcinoma.

Qu, Chao / Zeng, Piao-E / Wang, Hang-Yan / Yuan, Chun-Hui / Yuan, Hui-Shu / Xiu, Dian-Rong

Journal of magnetic resonance imaging : JMRI

2022 Volume 55, Issue 6, Page(s) 1625–1632

Abstract: ... density, and tissue hypoxia. It can also perform multiparameter quantitative analysis of tumor tissue and ... upon tumor diagnosis. In recent years, neoadjuvant treatment for patients with borderline resectable PDAC has ... the postoperative survival. However, further developments are required to accurately assess the tumor response ...

Abstract	Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignant tumors of the human digestive system. Due to its insidious onset, many patients have already lost the opportunity for radical resection upon tumor diagnosis. In recent years, neoadjuvant treatment for patients with borderline resectable PDAC has been recommended by multiple guidelines to increase the resection rate of radical surgery and improve the postoperative survival. However, further developments are required to accurately assess the tumor response to neoadjuvant therapy and to select the population suitable for such treatment. Reductions in drug toxicity and the number of neoadjuvant cycles are also critical. At present, the clinical evaluation of neoadjuvant treatment is mainly based on several serological and imaging indicators; however, the unique characteristics of PDAC and the insufficient sensitivity and specificity of the markers render this system ineffective. The imaging evaluation system, magnetic resonance imaging (MRI), has its own unique imaging advantages compared with computed tomography (CT) and other imaging examinations. One key advantage is the ability to reflect the changes more rapidly in tumor tissue components, such as the degree of fibrosis, microvessel density, and tissue hypoxia. It can also perform multiparameter quantitative analysis of tumor tissue and changes, attributing to its increasingly important role in imaging evaluation, and potentially the evaluation of neoadjuvant treatment of pancreatic cancer, as several current articles have studied. At the same time, owing to the complexity of MRI and some of its limitations, its wider application is limited. Compared with CT imaging, few relevant studies have been conducted. In this review article, we will investigate and summarize the advantages, limitations, and future development of MRI in the evaluation of neoadjuvant treatment of PDAC. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.
MeSH term(s)	Adenocarcinoma ; Carcinoma, Pancreatic Ductal/drug therapy ; Carcinoma, Pancreatic Ductal/therapy ; Humans ; Magnetic Resonance Imaging ; Neoadjuvant Therapy ; Pancreatic Neoplasms/diagnostic imaging ; Pancreatic Neoplasms/therapy ; Pancreatic Neoplasms
Language	English
Publishing date	2022-02-08
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1146614-5
ISSN	1522-2586 ; 1053-1807
ISSN (online)	1522-2586
ISSN	1053-1807
DOI	10.1002/jmri.28096
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Zs.A 3648: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Fe-doped nanodiamond-based photo-Fenton catalyst for dual-modal fluorescence imaging and improved chemotherapeutic efficacy against tumor hypoxia.

Selvam, Rajakar / Pearl, Wrenit Gem / Perevedentseva, Elena / Karmenyan, Artashes / Cheng, Chia-Liang

RSC advances

2024 Volume 14, Issue 6, Page(s) 4285–4300

Abstract: The deficiency of oxygen in most solid tumors plays a profound role in their proliferation ... adsorbed onto the FeND to address this issue. The conjugated DOX could undergo a redox cycle to generate ...

Abstract	The deficiency of oxygen in most solid tumors plays a profound role in their proliferation, metastasis, and invasion and contributes to their resistance to treatments such as radiation, chemotherapy, and photodynamic therapy (PDT). A therapeutic approach based on the Fenton reaction has received considerable interest as a means of treating cancer with ROS-based nano catalytic medicine, referred to as chemodynamic therapy (CDT). A range of modified treatment strategies are being explored to enhance both CDT and conventional methods of therapy. These include Fenton-like reactions, photo-enhanced Fenton reactions, and Fenton catalytic-enhanced synergistic therapies. In this article, we propose and demonstrate a photochemotherapy (PCT) strategy for cancer treatment utilizing near-infrared (NIR)-induced Fenton reactions using Fe-doped nanodiamond (FeND). When FeND is exposed to human lung cancer cells A549, it exhibits outstanding biocompatibility. However, when particle-treated cells are exposed to NIR laser radiation, the particle exhibits cytotoxicity to a certain degree. The anticancer medication doxorubicin (DOX) was adsorbed onto the FeND to address this issue. The conjugated DOX could undergo a redox cycle to generate excess H
Language	English
Publishing date	2024-01-31
Publishing country	England
Document type	Journal Article
ISSN	2046-2069
ISSN (online)	2046-2069
DOI	10.1039/d3ra08465e
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Article ; Online: Continuous monitoring of postirradiation reoxygenation and cycling hypoxia using electron paramagnetic resonance imaging.

Kawai, Tatsuya / Matsuo, Masayuki / Takakusagi, Yoichi / Saito, Keita / Hyodo, Fuminori / Devasahayam, Nallathamby / Matsumoto, Shingo / Kishimoto, Shun / Yasui, Hironobu / Yamamoto, Kazutoshi / Krishna, Murali C

NMR in biomedicine

2022 Volume 35, Issue 10, Page(s) e4783

Abstract: Reoxygenation has a significant impact on the tumor response to radiotherapy. With developments ... of interest. Evaluating the reoxygenation in the tumor microenvironment throughout the course ... paramagnetic resonance imaging (EPRI) to directly map and quantify the partial oxygen pressure (pO ...

Abstract	Reoxygenation has a significant impact on the tumor response to radiotherapy. With developments in radiotherapy technology, the relevance of the reoxygenation phenomenon in treatment efficacy has been a topic of interest. Evaluating the reoxygenation in the tumor microenvironment throughout the course of radiation therapy is important in developing effective treatment strategies. In the current study, we used electron paramagnetic resonance imaging (EPRI) to directly map and quantify the partial oxygen pressure (pO
MeSH term(s)	Animals ; Cell Hypoxia ; Electron Spin Resonance Spectroscopy/methods ; Female ; Humans ; Hypoxia ; Mice ; Mice, Nude ; Neoplasms ; Oxygen/metabolism ; Tumor Microenvironment
Chemical Substances	Oxygen (S88TT14065)
Language	English
Publishing date	2022-06-27
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Intramural
ZDB-ID	1000976-0
ISSN	1099-1492 ; 0952-3480
ISSN (online)	1099-1492
ISSN	0952-3480
DOI	10.1002/nbm.4783
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Zs.A 2869: Show issues

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Article: [Imaging of Tumor-Specific Hypoxia Dynamics and Its Significance in Radiation Biology].

Yasui, Hironobu / Matsumoto, Shingo / Inanami, Osamu / Krishna, Murali Cherukuri

Igaku butsuri : Nihon Igaku Butsuri Gakkai kikanshi = Japanese journal of medical physics : an official journal of Japan Society of Medical Physics

2020 Volume 40, Issue 1, Page(s) 13–18

Abstract: ... monitor fluctuating oxygenation i.e. cycling hypoxia in transplanted tumors. A common resonator platform ... Hypoxia has been known to be a feature associated with tumor radioresistance. So far, clinical ... However, intermittent or acute/cycling hypoxia, whose frequency can range between a few cycles per minutes to hours, is ...

Abstract	Hypoxia has been known to be a feature associated with tumor radioresistance. So far, clinical strategies to overcome chronic hypoxia due to the limitation of the oxygen diffusion have been designed. However, intermittent or acute/cycling hypoxia, whose frequency can range between a few cycles per minutes to hours, is receiving increased attention, because this type of hypoxia has been reported to have an influence on tumor malignancy as well as treatment resistance via increased expression of pro-survival pathways. Therefore, a priori information on fluctuating hypoxia can be important in clinical treatment planning, but complicated dynamics makes it difficult to elucidate biological significance of intermittent hypoxia.Here, we illustrate the use of pulsed electron spin resonance imaging (ESRI) as a novel imaging method to directly monitor fluctuating oxygenation i.e. cycling hypoxia in transplanted tumors. A common resonator platform for both ESRI and magnetic resonance imaging (MRI) provided pO
MeSH term(s)	Electron Spin Resonance Spectroscopy ; Humans ; Hypoxia ; Neoplasms/diagnostic imaging ; Neoplasms/physiopathology ; Oxygen ; Radiobiology ; Tumor Hypoxia
Chemical Substances	Oxygen (S88TT14065)
Language	Japanese
Publishing date	2020-03-31
Publishing country	Japan
Document type	Journal Article
ISSN	1345-5354
ISSN	1345-5354
DOI	10.11323/jjmp.40.1_13
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Article ; Online: Cyclic changes in T2* relaxometry of human uterus during the menstrual cycle using BOLD MR imaging.

Li, Yajie / Lai, Mao / Li, Qing / Fu, Caixia / Zhang, Qi

European journal of radiology

2022 Volume 156, Page(s) 110563

Abstract: ... monitoring hypoxia in gynecological tumors. ... myometrium during the menstrual cycle using blood oxygen level-dependent (BOLD) magnetic resonance imaging ... T2-weighted imaging and BOLD MR imaging. Multi-gradient-recalled echo (MGRE) sequence was used ...

Abstract	Purpose: To evaluate dynamic changes of T2* values within the endometrium, junctional zone and myometrium during the menstrual cycle using blood oxygen level-dependent (BOLD) magnetic resonance imaging. Method: Volunteers underwent MRI scans on menstrual phase, ovulatory phase and luteal phase, including T2-weighted imaging and BOLD MR imaging. Multi-gradient-recalled echo (MGRE) sequence was used to obtain BOLD MR images. T2* values of different uterine layers, including endometrium, junctional zone and myometrium, on sagittal images were analyzed quantitatively. Results: Twenty-four subjects calculated T2* values successfully. The T2* values of each zonal structure during menstruation were significantly lower than those during ovulatory phase (P < 0.05) and luteal phase (P < 0.001). The T2* value of junctional zone was significantly lower than that of the myometrium over all three menstrual phases (P = 0.000, menstrual; P = 0.000, ovulatory; P = 0.001, luteal). The mean T2* value in endometrium during the ovulatory phase was the highest of the uterine zones over menstrual cycle. During menstrual phase, there was no statistical difference between endometrium and junctional zone (P > 0.05). Conversely, the comparison of the T2* values between endometrium and myometrium, junctional zone and myometrium both showed significant difference (P = 0.000). The mean T2* values within endometrium during ovulatory phase and luteal phase were significantly higher than those within junctional zone and myometrium (P < 0.05). Conclusions: Cyclic changes of T2* values in each zonal structure of the uterus were revealed during the menstrual cycle by means of BOLD technique, which may be potentially beneficial in investigating dysmenorrhea, guiding assisted reproductive technologies and monitoring hypoxia in gynecological tumors.
MeSH term(s)	Female ; Humans ; Uterus/diagnostic imaging ; Menstrual Cycle ; Magnetic Resonance Imaging/methods ; Myometrium ; Endometrium
Language	English
Publishing date	2022-10-17
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	138815-0
ISSN	1872-7727 ; 0720-048X
ISSN (online)	1872-7727
ISSN	0720-048X
DOI	10.1016/j.ejrad.2022.110563
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Zs.A 1630: Show issues

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Article ; Online: Rational construction of a reversible arylazo-based NIR probe for cycling hypoxia imaging in vivo.

Zhang, Yuming / Zhao, Wenxuan / Chen, Yuncong / Yuan, Hao / Fang, Hongbao / Yao, Shankun / Zhang, Changli / Xu, Hongxia / Li, Nan / Liu, Zhipeng / Guo, Zijian / Zhao, Qingshun / Liang, Yong / He, Weijiang

Nature communications

2021 Volume 12, Issue 1, Page(s) 2772

Abstract: ... HDSF) for cycling hypoxia imaging. HDSF displays an off-on fluorescence switch at 705 nm in normoxia ... provides an effective strategy to construct organic fluorescent probes for cycling hypoxia imaging and ... tracking of cycling hypoxia in vivo. However, almost all of the reported organic fluorescent hypoxia probes ...

Abstract	Reversible NIR luminescent probes with negligible photocytotoxicity are required for long-term tracking of cycling hypoxia in vivo. However, almost all of the reported organic fluorescent hypoxia probes reported until now were irreversible. Here we report a reversible arylazo-conjugated fluorescent probe (HDSF) for cycling hypoxia imaging. HDSF displays an off-on fluorescence switch at 705 nm in normoxia-hypoxia cycles. Mass spectroscopic and theoretical studies confirm that the reversible sensing behavior is attributed to the two electron-withdrawing trifluoromethyl groups, which stabilizes the reduction intermediate phenylhydrazine and blocks the further reductive decomposition. Cycling hypoxia monitoring in cells and zebrafish embryos is realized by HDSF using confocal imaging. Moreover, hypoxic solid tumors are visualized and the ischemia-reperfusion process in mice is monitored in real-time. This work provides an effective strategy to construct organic fluorescent probes for cycling hypoxia imaging and paves the way for the study of cycling hypoxia biology.
MeSH term(s)	Animals ; Cell Hypoxia/physiology ; Cell Line, Tumor ; Female ; Fluorescent Dyes/chemistry ; Humans ; Ischemia/diagnostic imaging ; MCF-7 Cells ; Mice ; Mice, Inbred ICR ; Microscopy, Confocal ; Neoplasms/diagnostic imaging ; Optical Imaging/methods ; Reperfusion Injury/diagnostic imaging ; Single-Cell Analysis/methods ; Zebrafish/embryology
Chemical Substances	Fluorescent Dyes
Language	English
Publishing date	2021-05-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-021-22855-0
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