PET Imaging of Cardiac Hypoxia: Hitting Hypoxia Where It Hurts

Purpose of ReviewIn this review, we outline the potential for hypoxia imaging as a diagnostic and prognostic tool in cardiology. We describe the lead hypoxia PET radiotracers currently in development and propose a rationale for how they should most appropriately be screened and validated.Recent FindingsWhile the majority of hypoxia imaging agents has been developed for oncology, the requirements for hypoxia imaging in cardiology are different. Recent work suggests that the bis(thiosemicarbazone) family of compounds may be capable of detecting the subtle degrees of hypoxia associated with cardiovascular syndromes, and that they have the potential to be “tuned” to provide different tracers for different applications.SummaryNew tracers currently in development show significant promise for imaging evolving cardiovascular disease. Fundamental to their exploitation is their careful, considered validation and characterization so that the information they provide delivers the greatest prognostic insight achievable.

• Publication year

  2018

• Venue

  Current Cardiovascular Imaging Reports

• Publication date

  2018-02-23

• Fields of study

  Medicine

• Identifiers
  DOI 10.1007/s12410-018-9447-3PMID 29515752PMCID 5830463
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Vascular Imaging With 18F-Fluorodeoxyglucose Positron Emission Tomography Is Influenced by Hypoxia

  2017cited by this paper
• Quantitative Assessment of Coronary Microvascular Function: Dynamic Single-Photon Emission Computed Tomography, Positron Emission Tomography, Ultrasound, Computed Tomography, and Magnetic Resonance Imaging.

  2017cited by this paper
• 18F-fluoromisonidazole (FMISO) PET may have the potential to detect cardiac sarcoidosis

  2017cited by this paper
• Copper complexes with dissymmetrically substituted bis(thiosemicarbazone) ligands as a basis for PET radiopharmaceuticals: control of redox potential and lipophilicity.

  2017cited by this paper
• Impairment of Coronary Flow Reserve Evaluated by Phase Contrast Cine‐Magnetic Resonance Imaging in Patients With Heart Failure With Preserved Ejection Fraction

  2016cited by this paper
• Hypoxic control of metastasis

  2016cited by this paper
• Growing Evidence Linking Microvascular Dysfunction With Heart Failure With Preserved Ejection Fraction

  2016cited by this paper
• Imaging of hypoxia in mouse atherosclerotic plaques with (64)Cu-ATSM.

  2016cited by this paper
• Positron emission tomography imaging of coronary atherosclerosis

  2016cited by this paper
• PET/MRI of Hypoxic Atherosclerosis Using 64Cu-ATSM in a Rabbit Model

  2016cited by this paper
• Imaging atherosclerosis with positron emission tomography.

  2016cited by this paper
• 64Cu-CTS: A Promising Radiopharmaceutical for the Identification of Low-Grade Cardiac Hypoxia by PET

  2015cited by this paper
• In Vivo Imaging of Hypoxia in Atherosclerotic Plaques in Humans.

  2015cited by this paper
• The tumour microenvironment after radiotherapy: mechanisms of resistance and recurrence

  2015cited by this paper
• A comparative study of the hypoxia PET tracers [¹⁸F]HX4, [¹⁸F]FAZA, and [¹⁸F]FMISO in a preclinical tumor model.

  2015cited by this paper
• Molecular imaging of hypoxia in non-small-cell lung cancer

  2015cited by this paper
• PET imaging of inflammation in atherosclerosis

  2014cited by this paper
• Diagnosis and Management of Heart Failure with Preserved Ejection Frac-tion: 10 Key Lessons

  2014cited by this paper
• Noninvasive Assessment of Hypoxia in Rabbit Advanced Atherosclerosis Using 18F-fluoromisonidazole Positron Emission Tomographic Imaging

  2014cited by this paper
• Hypoxia-inducible factor 1 and cardiovascular disease.

  2014cited by this paper
• Cardiac Hypoxia Imaging: Second-Generation Analogues of 64Cu-ATSM

  2014cited by this paper
• Modification of intracellular glutathione status does not change the cardiac trapping of 64Cu(ATSM)

  2014cited by this paper
• The pathophysiology of heart failure with preserved ejection fraction

  2014cited by this paper
• Coronary microvascular dysfunction.

  2013cited by this paper
• Demonstration of the retention of 64Cu-ATSM in cardiac myocytes using a novel incubation chamber for screening hypoxia-dependent radiotracers

  2013cited by this paper
• Hypoxia imaging with the nitroimidazole 18F-FAZA PET tracer: a comparison with OxyLite, EPR oximetry and 19F-MRI relaxometry.

  2012cited by this paper
• Hypoxia imaging with PET: which tracers and why?

  2012cited by this paper
• PET imaging of cardiac hypoxia: opportunities and challenges.

  2011cited by this paper
• Hypoxia but not inflammation augments glucose uptake in human macrophages: Implications for imaging atherosclerosis with 18fluorine-labeled 2-deoxy-D-glucose positron emission tomography.

  2011cited by this paper
• Copper complexes of bis(thiosemicarbazones): from chemotherapeutics to diagnostic and therapeutic radiopharmaceuticals.

  2011cited by this paper
• Significance and assessment of coronary microvascular dysfunction

  2011cited by this paper
• Molecular Imaging of Hypoxia

  2011cited by this paper
• Detection of Hypoxia by [18F]EF5 in Atherosclerotic Plaques in Mice

  2011cited by this paper
• Primary Coronary Microvascular Dysfunction: Clinical Presentation, Pathophysiology, and Management

  2010cited by this paper
• Feasibility of FDG imaging of the coronary arteries: comparison between acute coronary syndrome and stable angina.

  2010cited by this paper
• Imaging atherosclerotic plaque inflammation by fluorodeoxyglucose with positron emission tomography: ready for prime time?

  2010cited by this paper
• Some thoughts on the mechanism of cellular trapping of Cu(II)-ATSM.

  2010cited by this paper
• Hexokinase-mitochondrial interaction in cardiac tissue: implications for cardiac glucose uptake, the 18FDG lumped constant and cardiac protection

  2009cited by this paper
• Molecular Imaging of Hypoxia

  2008cited by this paper
• Suppression of myocardial 18F-FDG uptake by preparing patients with a high-fat, low-carbohydrate diet.

  2008cited by this paper
• Hypoxia, hypoxia-inducible transcription factor, and macrophages in human atherosclerotic plaques are correlated with intraplaque angiogenesis.

  2008cited by this paper
• Metabolic imaging using PET

  2007cited by this paper
• Coronary Microvascular Dysfunction

  2007cited by this paper
• Hypoxia positron emission tomography imaging with 18f-fluoromisonidazole.

  2007cited by this paper
• T2 measurement of the human myocardium using a T2‐prepared transient‐state trueFISP sequence

  2007cited by this paper
• Molecular Mechanisms in Heart Failure: Focus on Cardiac Hypertrophy, Inflammation, Angiogenesis, and Apoptosis

  2006cited by this paper
• Altered Creatine Kinase Adenosine Triphosphate Kinetics in Failing Hypertrophied Human Myocardium

  2006cited by this paper
• Trends in prevalence and outcome of heart failure with preserved ejection fraction.

  2006cited by this paper
• In vivo 18F-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients.

  2006cited by this paper
• Oxygen, oxidative stress, hypoxia, and heart failure.

  2005cited by this paper
• Investigation into 64Cu-labeled Bis(selenosemicarbazone) and Bis(thiosemicarbazone) complexes as hypoxia imaging agents.

  2005cited by this paper
• Cardiac substrate uptake and metabolism in obesity and type-2 diabetes: Role of sarcolemmal substrate transporters

  2005cited by this paper
• Cardiac positron emission tomography imaging.

  2005cited by this paper
• A Metabolic Marker of Myocyte Hypoxia

  2005cited by this paper
• Surrogate Markers for Cardiovascular Disease: Functional Markers

  2004cited by this paper
• Influence of blood glucose level, age and fasting period on non-pathological FDG uptake in heart and gut

  2004cited by this paper
• Inflammation and Atherosclerosis

  2004cited by this paper
• The Imbalance Between Oxygen Demand and Supply as a Potential Mechanism in the Pathophysiology of Heart Failure: The Role of Microvascular Growth and Abnormalities

  2003influential reference
• Inflammation and Atherosclerosis

  2002cited by this paper
• Copper bis(thiosemicarbazone) complexes as hypoxia imaging agents: structure-activity relationships

  2002cited by this paper
• Imaging Atherosclerotic Plaque Inflammation With [18F]-Fluorodeoxyglucose Positron Emission Tomography

  2002cited by this paper
• Studies on the mechanism of hypoxic selectivity in copper bis(thiosemicarbazone) radiopharmaceuticals.

  2002cited by this paper
• Calibrated histochemistry applied to oxygen supply and demand in hypertrophied rat myocardium

  2002cited by this paper
• Measurement of Tumor Oxygenation: In Vivo Comparison of a Luminescence Fiber-optic Sensor and a Polarographic Electrode in the P22 Tumor

  2001cited by this paper
• Imaging hypoxia in tumors.

  2001cited by this paper
• Copper-62 ATSM as a hypoxic tissue tracer in myocardial ischemia

  2001cited by this paper
• The isolated blood and perfusion fluid perfused heart.

  2000cited by this paper
• Abnormal myocardial phosphorus-31 nuclear magnetic resonance spectroscopy in women with chest pain but normal coronary angiograms.

  2000cited by this paper
• Prognostic impact of coronary vasodilator dysfunction on adverse long-term outcome of coronary heart disease.

  2000cited by this paper
• The potential for myocardial imaging with hypoxia markers.

  1999cited by this paper
• Evidence of hypoxic areas within the arterial wall in vivo.

  1999cited by this paper
• Comparative studies of Cu-64-ATSM and C-11-acetate in an acute myocardial infarction model: ex vivo imaging of hypoxia in rats.

  1999cited by this paper
• Atherosclerosis--an inflammatory disease.

  1999cited by this paper
• Design of hypoxia-targeting radiopharmaceuticals: selective uptake of copper-64 complexes in hypoxic cells in vitro

  1998cited by this paper
• Copper-62-ATSM: a new hypoxia imaging agent with high membrane permeability and low redox potential.

  1997cited by this paper
• Myocardial signal response to dipyridamole and dobutamine: Demonstration of the BOLD effect using a double‐echo gradient‐echo sequence

  1996cited by this paper
• Quantifying regional hypoxia in human tumors with positron emission tomography of [18F]fluoromisonidazole: a pretherapy study of 37 patients.

  1996cited by this paper
• Nitroimidazoles and imaging hypoxia

  1995cited by this paper
• Nitroimidazoles for imaging hypoxic myocardium

  1995cited by this paper
• Quantitative measurements of cardiac phosphorus metabolites in coronary artery disease by 31P magnetic resonance spectroscopy.

  1995cited by this paper
• Cu-ATSM, an intracellular-accessible superoxide dismutase (SOD)-like copper complex: evaluation in an ischemia-reperfusion injury model.

  1994cited by this paper
• In vivo delineation of myocardial hypoxia during coronary occlusion using fluorine-18 fluoromisonidazole and positron emission tomography: a potential approach for identification of jeopardized myocardium.

  1990cited by this paper
• Fluoromisonidazole. A metabolic marker of myocyte hypoxia.

  1990cited by this paper
• A new zinc-62/copper-62 generator as a copper-62 source for PET radiopharmaceuticals.

  1989cited by this paper
• Myocardial kinetics of fluorine-18 misonidazole: a marker of hypoxic myocardium.

  1989cited by this paper
• Oxygen tensions in lesions of experimental atherosclerosis of rabbits.

  1973cited by this paper
• Arterial Hypoxemia Following Acute Myocardial Infarction

  1969cited by this paper

• Emerging tracers for cardiac imaging: Innovations and clinical implications.

  2025cites this paper
• [99mTc]Technetium and Rhenium Dithiocarbazate Complexes: Chemical Synthesis and Biological Assessment

  2025cites this paper
• Perfusion-Independent Tissue Hypoxia in Cardiac Hypertrophy in Mice Measured by 64Cu-CTS PET Imaging

  2024cites this paper
• Applications of radiocomplexes with thiosemicarbazones and bis(thiosemicarbazones) in diagnostic and therapeutic nuclear medicine

  2022cites this paper
• Detection of cardiac apoptosis by [18F]ML-10 in a mouse model of permanent LAD ligation

  2022cites this paper
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  2022cites this paper
• Correlation of hypoxia PET tracer uptake with hypoxic radioresistance in cancer cells: PET biomarkers of resistance to stereotactic radiation therapy?

  2022cites this paper
• Detection of apoptosis by [18F]ML-10 after cardiac ischemia–reperfusion injury in mice

  2022cites this paper
• Application of Metabolic Reprogramming to Cancer Imaging and Diagnosis

  2022cites this paper
• Cardiac 18F-FDG Positron Emission Tomography: An Accurate Tool to Monitor In vivo Metabolic and Functional Alterations in Murine Myocardial Infarction

  2021cites this paper
• Novel Tracers and Radionuclides in PET Imaging.

  2021cites this paper
• The cellular basis of increased PET hypoxia tracer uptake in focal cerebral ischemia with comparison between [18F]FMISO and [64Cu]CuATSM

  2020cites this paper
• Penumbra oxygen metabolism and acute neuroinflammation in ischemic stroke : MRI and PET imaging of a M2 occlusion model in rat

  2020cites this paper
• Tissue acidosis does not mediate the hypoxia selectivity of [64Cu][Cu(ATSM)] in the isolated perfused rat heart

  2019cites this paper
• Current and Future Cardiovascular PET Radiopharmaceuticals.

  2019cites this paper
• Cu ( ATSM ) ] in the isolated perfused rat heart

  2019cites this paper
• Melanin-based nanoparticles in biomedical applications: From molecular imaging to treatment of diseases

  2019cites this paper