Hypoxia is a pathological condition in which the body as a whole (generalised hypoxia) or region of the body (tissue hypoxia) is deprived of adequate oxygen supply. Hypoxia in which there is complete deprivation of oxygen supply is referred to as anoxia.

Generalized hypoxia occurs in healthy people when they ascend to high altitude, where it causes altitude sickness, and the potentially fatal complications of altitude sickness, high altitude pulmonary oedema (HAPE) and high altitude cerebral oedema (HACE). Hypoxia also occurs in healthy individuals when breathing mixtures of gases with a low oxygen content, for example while diving underwater, especially with closed-circuit rebreather systems that control the amount of oxygen in the air breathed in. Altitude training uses mild hypoxia to increase the concentration of red blood cells in the body for increased athletic performance.

2-Nitroimidazole

• immunohistochemical detection of a hypoxia marker in spontaneous canine tumours. PMID: 1701659
• potential utility of the 2-nitroimidazole derivatives of the amine-dioxime class of chelator as hypoxia-targeting agents. PMID: 10995208
• 2-Nitroimidazole hypoxia markers show considerable promise for clinical use in diagnosing hypoxia and their use could allow rational application of hypoxia-related therapies to those patients most likely to benefit from them. PMID: 9755725

[(18)F]FRP-170

• a novel hypoxic cell marker. PMID: 15763476

99mTc-HL91

• 99mTc-HL91 scintigraphy may be useful for evaluating oxygenation status of some tumors in non-abdominal region. PMID: 11530380
• 99mTc-HL91 (Prognox) shows good potential as a clinical marker for hypoxia and warrants further development. PMID: 9845086

99mTc-BMS181321

• well trapped in ischemic myocardium and moderately trapped in hypoxic myocardium, but washed out quickly in stunned myocardium. PMID: 8046496

A2 and A4

• showed a very large differential fluorescence between hypoxic and oxic cells (V79 cells) in vitro and are promising candidate markers for hypoxic cells. PMID: 16403640

BMS181321

• a useful agent to investigate the status of hypoxia in solid tumors experimentally and potentially in the clinic. PMID: 8683295

Carbonic Anhydrase 9 (CA9, CA IX)

• the endogenous hypoxia marker. PMID: 17200340, PMID: 15069539
• an endogenous marker of chronic hypoxia in live human tumor cells. PMID: 15752902
• one of the most inducible and most uniformly induced genes and because of its stability and membrane location provides a reliable histochemical marker of hypoxia. PMID: 14712082
• a novel surrogate marker of tumor hypoxia, is associated with a poor prognosis in non-small-cell lung cancer. PMID: 12560438
• a potential new intrinsic marker of hypoxia: correlations with tumor oxygen measurements and prognosis in locally advanced carcinoma of the cervix. PMID: 11522632
• a transmembrane protein overexpressed in a wide variety of tumor types and induced by hypoxia, is a useful endogenous marker of tumor hypoxia. PMID: 11751418
• regulated by hypoxia inducible factor-1 (HIF-1) and has been studied as putative intrinsic cellular markers for hypoxia. PMID: 14520462

CCI-103F

• a 2-nitroimidazole hypoxia marker. PMID: 9288846, PMID: 8286212
• CCI-103F labeling of hypoxic regions in tumors provides a nonradioactive method of detecting nitroimidazole adducts at the cellular level, and allows concurrent histologic examination. PMID: 8138446

Clusterin

• a secreted marker for a hypoxia-inducible factor-independent function of the von Hippel-Lindau tumor suppressor protein. PMID: 16436671

CREB (cAMP response element binding protein)

• CREB phosphorylation may be employed as an in situ marker for hypoxia. PMID: 16598418

CSF CK-BB and NSE

• are useful prognostic indicators of hypoxic brain injury when measured 28-76 h after cardiac arrest whereas blood samples have no prognostic value. PMID: 8509798

DEC1 (differentiated embryo-chondrocyte expressed gene 1)

• a marker of tumor hypoxia. DEC1 downregulates the HIF-1alpha at both mRNA and protein levels at hypoxia in lung adenocarcinoma A549 cells. PMID: 17376295

EF1

• a non-invasive hypoxia marker with detection using positron emission tomography (PET). PMID: 10581679

EF3

• Synthesis of [18F]-labeled EF3 [2-(2-nitroimidazol-1-yl)-N-(3,3,3-trifluoropropyl)-acetamide], a marker for PET detection of hypoxia. PMID: 11310602
• a hypoxia marker. PMID: 10825135

EF5

• a chemical probe for hypoxia. PMID: 8521417

EGFR (epidermal growth-factor receptor)

• intrinsic markers of hypoxia. PMID: 16618579

Erythropoietin

• a marker of chronic fetal hypoxia. PMID: 9544710

Fibrotic Focus (FF)

• a marker of intra-tumoral hypoxia in invasive breast carcinoma, is useful as a surrogate marker of hypoxia-driven ongoing angiogenesis and is associated with a higher relapse rate and a worse overall survival. PMID: 14572156

Fluoromisonidazole

• a metabolic marker of myocyte hypoxia. PMID: 2364494

GLUT-1 (glucose transporter-1)

• endogenous hypoxic marker. PMID: 16944372
• regulated by hypoxia inducible factor-1 (HIF-1) and has been studied as putative intrinsic cellular markers for hypoxia. PMID: 14520462
• validated as intrinsic markers of hypoxia by comparison with pO(2) measured using oxygen electrodes. PMID: 12532423

GLUT-3 (glucose transporter-3)

• the putative endogenous hypoxia marker. PMID: 16730088

Hypoxia-inducible factors (HIF-1 and HIF-2)

• two closely related protein complexes that activate transcription of target genes in response to hypoxia. PMID: 11156418

HIF-1alpha (Hypoxia-inducible factor-1alpha)

• a subunit of hypoxia-inducible factor-1 (HIF-1), furnishes tumor cells with the means of adapting to stress parameters, such as tumor hypoxia. PMID: 16512994
• a key regulatory element of the hypoxic response of cells. High protein levels have been linked to poor prognosis in several tumor types, and HIF-1alpha has been suggested as a potential endogenous marker of tumor hypoxia and associated radioresistance. PMID: 12829158
• a useful intrinsic marker for hypoxia in cervical carcinoma xenografts. PMID: 11606368

HIF-2alpha (Hypoxia-inducible factor-2alpha)

• HIF-1alpha and HIF-2alpha may have distinct roles in responses to environmental stress, and despite its name, HIF-2alpha may be more important in the survival response to environmental variables other than the level of oxygen. PMID: 11546756
• HIF-2alpha was also strongly expressed within subsets of normal bone marrow macrophages. PMID: 10934146

HIHIG2 (Hypoxia-inducible protein 2)

• a novel diagnostic marker for renal cell carcinoma and potential target for molecular therapy. PMID: 15930302

IAZA

• a novel marker of tissue hypoxia. PMID: 12672991, PMID: 1880579

Involucrin

• endogenous hypoxic marker. PMID: 16944372

IVM (iodovinylmisonidazole)

• a promising marker for myocardial hypoxia with potential clinical application using gamma camera imaging. PMID: 8509858

IAZP (Radioiodinated azomycin pyranoside)

• a novel non-invasive marker for the assessment of tumor hypoxia. PMID: 1450228

Lactate

• a marker for tissue hypoxia, the skeletal muscle as well as the liver may consume lactate under hypoxic hypoxia. PMID: 14530936
• a classic companion of hypoxic stress in mammals, is a modulator of hypoxia-induced hyperventilation. PMID: 14519376

LDH5

• transcriptionally regulated by the hypoxia inducible factors (HIF) 1alpha and 2alpha. PMID: 16132575

M75

• a promising tool for selective immunotargeting of hypoxic human tumors that express CA IX. PMID: 12767076

Neopterin

• elevated in infections, autoimmune diseases and post-transplant, is an early marker of surgical stress and hypoxic reperfusion damage during liver surgery. PMID: 12241010

NLTQ-1

• a new bioreductive agent as a hypoxia marker by 19F-magnetic resonance spectroscopy (19F-MRS). PMID: 11695231

Osteopontin (OPN)

• recognized as a tumor-associated protein and has recently been shown to be a potential plasma marker of tumor hypoxia in head and neck cancer patients. PMID: 16024111
• endogenous hypoxic marker. PMID: 16944372

PCO2

• universal marker of tissue hypoxia. PMID: 10965713

Pimonidazole

• a novel hypoxia marker, can be used for qualitative and quantitative assessment of tumor hypoxia. PMID: 9826471, PMID: 9731480, PMID: 9654074, PMID: 11169851

S100

• Early determination of serum S100 may reflect the extent of brain damage in infants with HIE after asphyxia. PMID: 14630979
• Astroglial protein S-100 is an early and sensitive marker of hypoxic brain damage and short-term outcome after cardiac arrest in humans. PMID: 11390339

SR-4554

• a noninvasive hypoxia marker detected by magnetic resonance spectroscopy. PMID: 12114437

Succinate

• may be a clinically useful marker for hypoxia in patients after blood transfusion. PMID: 9098517

Troponin T

• is more sensitive in the identification of infants with asphyxia and cardiocirculatory failure than creatinine. PMID: 9618054

U0126

• a specific inhibitor of MEK1/2, downregulated CAIX expression induced by true hypoxia and cell density. PMID: 16270297

VEGF (vascular endothelial growth factor)

• endogenous hypoxic marker. PMID: 16944372

Other Hypoxia Markers

• Oral pimonidazole HCl is effective as a hypoxia marker in spontaneously arising canine tumors. Selective cellular uptake and concomitant higher levels of binding in regions of hypoxia at the high end of pH gradients might account for the greater extent of pimonidazole binding. PMID: 16289910
• The 5HRE beta-hCG reporter system described here enables serial, noninvasive monitoring of tumor hypoxia in a mouse model by measuring a urinary reporter protein. PMID: 16024616
• [(18)F]FETA shows hypoxia-dependent tumour retention and is, thus, a promising PET marker that warrants clinical evaluation. PMID: 15150578
• Preparation and biodistribution of technetium-99m-labeled 1-(2-nitroimidazole-1-yl)-propanhydroxyiminoamide (N2IPA) as a tumor hypoxia marker. PMID: 15013485
• A new paraclinical CSF marker for hypoxia-like tissue damage in multiple sclerosis lesions. PMID: 12764056
• Technetium-99m-cyclam AK 2123: a novel marker for tumor hypoxia. PMID: 11144256
• [18F]-EF5 should be well suited for use as a non-invasive hypoxia marker with detection using positron emission tomography (PET). PMID: 11144255
• Changes in tumor hypoxia measured with a double hypoxic marker technique. PMID: 11121659
• high HL91 uptake is related to low blood flow. The marked HL91 uptake around the necrotic region suggests the presence of chronic hypoxia in a tumour. PMID: 9933342
• Lipid peroxidation in cord blood at birth: a marker of fetal hypoxia during labour. PMID: 9415519
• Evaluation of the role of cellular hypoxia in sepsis by the hypoxic marker [18F]fluoromisonidazole. PMID: 1928443
• Misonidazole binding in murine liver tissue: a marker for cellular hypoxia in vivo. PMID: 2792663
• Conversion of xanthine dehydrogenase to xanthine oxidase as a possible marker for hypoxia in tumours and normal tissues. PMID: 2765364
• Nitrate reduction as a marker for hypoxic shiftdown of Mycobacterium tuberculosis. PMID: 10645451
• A dual hypoxic marker technique for measuring oxygenation change within individual tumors. PMID: 9683288
• A rapid and simple assay to determine the blood and urine concentrations of 1-(5-[123/125I]iodo-5-deoxyarabinofuranosyl)-2-nitroimidazole, a hypoxic cell marker. PMID: 9547711
• the presence of abundant microglia in the polymorphous layer of the dentate gyrus of human infants is a marker of chronic illness or mild hypoxic-ischaemic brain injury which takes several days to develop. PMID: 8072645
• Plasma hypoxanthine: a marker for hypoxic-ischaemic induced periventricular leucomalacia. PMID: 1586176
• Evaluation of the role of cellular hypoxia in sepsis by the hypoxic marker [18F]fluoromisonidazole. PMID: 1928443
• Myocardial kinetics of fluorine-18 misonidazole: a marker of hypoxic myocardium. PMID: 2738664
• [18F]fluoromisonidazole may be a suitable agent for radionuclide imaging of hypoxic myocardium. PMID: 2738648
• Misonidazole (MISO), a selective radiosensitizer of hypoxic cells, forms adducts with cellular biomolecules with rates which are 30-50 X higher under hypoxic as compared to aerobic conditions of incubation. PMID: 3952269
• Tumor microenvironment in head and neck squamous cell carcinomas: Predictive value and clinical relevance of hypoxic markers. A review. PMID: 17252597
• Synthesis and evaluation of novel 8-oxo-8H-cyclopenta[a]acenaphthylene-7-carbonitriles as long-wavelength fluorescent markers for hypoxic cells in solid tumor. PMID: 16403630
• In comparison with hypoxic hypoxia, critical values of SvO2 are higher in anemic hypoxia, indicating that oxygen unloading from blood to tissues is impaired in anemic hypoxia. PMID: 10507614
• Fluorescent markers for hypoxic cells: a study of nitroaromatic compounds, with fluorescent heterocyclic side chains, that undergo bioreductive binding. PMID: 2066999
• Fluorescent markers for hypoxic cells. A study of novel heterocyclic compounds that undergo bio-reductive binding. PMID: 1705123
• Fluorescent markers of hypoxic cells: a comparison of two compounds on three cell lines. PMID: 3839428
• the (99m)Tc labeled nitrobenzoimidazole and nitrotriazole might be the novel tumor hypoxia markers. PMID: 16460938
• Synthesis and in vitro and in vivo evaluation of three radioiodinated nitroimidazole analogues as tumor hypoxia markers. PMID: 15820757
• Comparison of the biodistribution of two hypoxia markers [18F]FETNIM and [18F]FMISO in an experimental mammary carcinoma. PMID: 14722675
• [99mTc]Technetium labelled PnAo-azomycin glucuronides: a novel class of imaging markers of tissue hypoxia. PMID: 12433047
• Both BRU59-21 and 99mTc-BnAO share properties making them suitable for hypoxia imaging. PMID: 11711315