ArticleJournal of nuclear medicine : official publication, Society of Nuclear Medicine2014
Cardiac hypoxia imaging: second-generation analogues of 64Cu-ATSM.
Article in Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 45 citations in OpenAlex.
- Sarcolemmal and mitochondrial membrane potentials measured ex vivo and in vivo in the heart by pharmacokinetic modelling of [The Journal of physiology · 2026Article
- Theranostic Potential of Copper-64 ATSM Targeting MTHFD2: An In Silico Perspective on Hypoxia-Selective Imaging and Therapy.Cell biochemistry and biophysics · 2025Article
- Hypoxia in Human Obesity: New Insights from Inflammation towards Insulin Resistance-A Narrative Review.International journal of molecular sciences · 2024Review
- Elevated Na is a dynamic and reversible modulator of mitochondrial metabolism in the heart.Nature communications · 2024Article
- Radiomic signatures from T2W and DWI MRI are predictive of tumour hypoxia in colorectal liver metastases.Insights into imaging · 2023Article
- Detecting Validated Intracellular ROS Generation withMolecular imaging and biology · 2022Article
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- 2020 FDA TIDES (Peptides and Oligonucleotides) Harvest.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Imaging of Chemotherapy-Induced Acute Cardiotoxicity withJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2019Article
- Tissue acidosis does not mediate the hypoxia selectivity of [Scientific reports · 2019Article
- Detection of anthracycline-induced cardiotoxicity using perfusion-correctedScientific reports · 2019Article
- PET Imaging of Cardiac Hypoxia: Hitting Hypoxia Where It Hurts.Current cardiovascular imaging reports · 2018Review
- Searching for novel PET radiotracers: imaging cardiac perfusion, metabolism and inflammation.American journal of nuclear medicine and molecular imaging · 2018Review
- Establishing Reliable Cu-64 Production Process: From Target Plating to Molecular Specific Tumor Micro-PET Imaging.Molecules (Basel, Switzerland) · 2017Article
- Cardioprotective effects of CuScientific reports · 2016Article
- Opportunities and challenges for metal chemistry in molecular imaging: from gamma camera imaging to PET and multimodality imaging.Advances in inorganic chemistry · 2016Article
- Creation of clinically relevant model of chronic heart failure: Application of multi-modality imaging to define physiology.Journal of nuclear cardiology : official publication of the American Society of Nuclear Cardiology · 2015Article
- Molecular imaging of hypoxia in non-small-cell lung cancer.European journal of nuclear medicine and molecular imaging · 2015Review
- A nuclear chocolate box: the periodic table of nuclear medicine.Dalton transactions (Cambridge, England : 2003) · 2015Review
- Evaluation of hypoxia with copper-labeled diacetyl-bis(N-methylthiosemicarbazone).Seminars in nuclear medicine · 2015Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
unlabelledMyocardial hypoxia is an attractive target for diagnostic and prognostic imaging, but current approaches are insufficiently sensitive for clinical use. The PET tracer copper(II)-diacetyl-bis(N4-methylthiosemicarbazone) ((64)Cu-ATSM) has promise, but its selectivity and sensitivity could be improved by structural modification. We have therefore evaluated a range of (64)Cu-ATSM analogs for imaging hypoxic myocardium.
methodsIsolated rat hearts (n = 5/group) were perfused with normoxic buffer for 30 min and then hypoxic buffer for 45 min within a custom-built triple-γ-detector system to quantify radiotracer infusion, hypoxia-dependent cardiac uptake, and washout. A 1-MBq bolus of each candidate tracer (and (18)F-fluoromisonidazole for comparative purposes) was injected into the arterial line during normoxia, and during early and late hypoxia, and their hypoxia selectivity and pharmacokinetics were evaluated. The in vivo pharmacokinetics of promising candidates in healthy rats were then assessed by PET imaging and biodistribution.
resultsAll tested analogs exhibited hypoxia sensitivity within 5 min. Complexes less lipophilic than (64)Cu-ATSM provided significant gains in hypoxic-to-normoxic contrast (14:1 for (64)Cu-2,3-butanedione bis(thiosemicarbazone) (ATS), 17:1 for (64)Cu-2,3-pentanedione bis(thiosemicarbazone) (CTS), 8:1 for (64)Cu-ATSM, P < 0.05). Hypoxic first-pass uptake was 78.2% ± 7.2% for (64)Cu-ATS and 70.7% ± 14.5% for (64)Cu-CTS, compared with 63.9% ± 11.7% for (64)Cu-ATSM. Cardiac retention of (18)F-fluoromisonidazole increased from 0.44% ± 0.17% during normoxia to 2.24% ± 0.08% during hypoxia. In vivo, normoxic cardiac retention of (64)Cu-CTS was significantly lower than that of (64)Cu-ATSM and (64)Cu-ATS (0.13% ± 0.02% vs. 0.25% ± 0.04% and 0.24% ± 0.03% injected dose, P < 0.05), with retention of all 3 tracers falling to less than 0.7% injected dose within 6 min. (64)Cu-CTS also exhibited lower uptake in liver and lung.
conclusion(64)Cu-ATS and (64)Cu-CTS exhibit better cardiac hypoxia selectivity and imaging characteristics than the current lead hypoxia tracers, (64)Cu-ATSM and (18)F-fluoromisonidazole.
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