Contribution of [64Cu]-ATSM PET in molecular imaging of tumour hypoxia compared to classical [18F]-MISO — a selected review

Bourgeois, Mickaël; Rajerison, Holisoa; Guérard, François; Mougin-Degraef, Marie; Barbet, Jacques; Michel, Nathalie; Chérel, Michel; Faivre-Chauvet, Alain

doi:10.5603/nmr.2011.00022

Cited by 68 publications

(53 citation statements)

References 39 publications

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“…Recently, the feasibility of this PET imaging agent for in vivo detection of hypoxia in advanced lesions was successfully evaluated in rabbits with advanced atherosclerosis (15). However, compared with 64 Cu-ATSM, 18 F-fluoromisonidazole has 2 major disadvantages: lower cellular uptake and slower washout from normoxic tissue (20). The more efficient uptake and washout kinetics of 64 Cu-ATSM in hypoxic and normoxic cells offer the possibility of a faster and more selective means of detecting hypoxia by PET imaging.…”

Section: Discussionmentioning

confidence: 99%

“…64 Cu-ATSM imaging would overcome this limitation. 18 F-fluoromisonidazole is one of the most commonly used investigational PET agents for the measurement of tumor hypoxia (20). Recently, the feasibility of this PET imaging agent for in vivo detection of hypoxia in advanced lesions was successfully evaluated in rabbits with advanced atherosclerosis (15).…”

Section: Discussionmentioning

confidence: 99%

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PET/MRI of Hypoxic Atherosclerosis Using ⁶⁴Cu-ATSM in a Rabbit Model

et al. 2016

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The macrophage-rich core of advanced human atheroma has been demonstrated to be hypoxic, which may have implications in plaque stability. The goal of this study was to determine the feasibility of the hypoxia PET imaging agent 64 Cu-ATSM to detect hypoxia in a rabbit model of atherosclerosis imaged on a simultaneous PET/MR scanner, using MR for both attenuation correction and depiction of lesion location. Methods: New Zealand White rabbits fed a Western diet for 4-6 wk underwent endothelial denudation of the right femoral artery by air desiccation to induce an atherosclerotic-like lesion and underwent a sham operation on the left femoral artery. Four and 8 wk after injury, a 0-to 60-min dynamic whole-body PET/MR examination was performed after injection of approximately 111 MBq of 64 Cu-ATSM. After 24 h, a 0-to 75-min dynamic PET/MR examination after injection of approximately 111 MBq of 18 F-FDG was performed. The rabbits were euthanized, and the injured femoral artery (IF) and sham-operated femoral artery (SF) were collected for immunohistochemistry assessment of hypoxic macrophages (hypoxia marker pimonidazole, macrophage marker RAM-11, and hypoxia-inducible factor-1 α subunit ). Regions of interest of IF, SF, and background muscle (BM) were drawn on fused PET/MR images, and IF-to-BM and SF-to-BM SUV ratios were compared using the Student t test. Results: Elevated uptake of 64 Cu-ATSM was found in the rabbits' IF compared with the SF. 64 Cu-ATSM imaging demonstrated IF-to-SF SUV mean ratios (±SD) of 1.75 ± 0.21 and 2.30 ± 0.26 at 4 and 8 wk after injury, respectively. 18 F-FDG imaging demonstrated IF-to-SF SUV mean ratios of 1.84 ± 0.12 at 8 wk after injury. IF-to-BM SUV mean ratios were significantly higher (P , 0.001) than SF-to-BM SUV mean ratios both 4 and 8 wk after injury for 64 Cu-ATSM and 8 wk after injury for 18 F-FDG (P , 0.05). Pimonidazole immunohistochemistry at 8 wk colocalized to RAM-11 and HIF-1α. Conclusion: The results show that hypoxia is present in this rabbit model of atherosclerosis and suggest that 64 Cu-ATSM PET/MR is a potentially promising method for the detection of hypoxic and potentially vulnerable atherosclerotic plaque in human subjects. At herosclerosis is a systemic degenerative and inflammatory vascular disease that develops over decades, leading to advanced lesions characterized by a lipid core separated from the lumen by a fibrous cap. It has been recognized that plaque composition more than the degree of luminal stenosis determines the risk of acute clinical events (e.g., stroke, myocardial infarction) (1). Macrophage-rich plaques with a thin fibrous cap, large lipid core, and abundance of leaky microvessels tend to be more vulnerable (1). The rupture or erosion of the fibrous cap in vulnerable plaque may lead to thromboembolization and arterial occlusion (2,3).According to the anoxemia theory of atherosclerosis, an imbalance between the demand for and supply of oxygen in the arterial wall is a key factor in the development of atherosclerotic lesions (4). In the initial s...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

PET/MRI of Hypoxic Atherosclerosis Using ⁶⁴Cu-ATSM in a Rabbit Model

et al. 2016

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“…Hypoxia can result in an increase in tumor aggressiveness, failure of local control, and activation of transcription factors that support cell survival and migration [57]. …”

Section: Clinical Applicationmentioning

confidence: 99%

The Copper Radioisotopes: A Systematic Review with Special Interest to⁶⁴Cu

Asabella

Cascini

Altini

et al. 2014

BioMed Research International

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Copper (Cu) is an important trace element in humans; it plays a role as a cofactor for numerous enzymes and other proteins crucial for respiration, iron transport, metabolism, cell growth, and hemostasis. Natural copper comprises two stable isotopes, 63Cu and 65Cu, and 5 principal radioisotopes for molecular imaging applications (60Cu, 61Cu, 62Cu, and 64Cu) and in vivo targeted radiation therapy (64Cu and 67Cu). The two potential ways to produce Cu radioisotopes concern the use of the cyclotron or the reactor. A noncopper target is used to produce noncarrier-added Cu thanks to a chemical separation from the target material using ion exchange chromatography achieving a high amount of radioactivity with the lowest possible amount of nonradioactive isotopes. In recent years, Cu isotopes have been linked to antibodies, proteins, peptides, and nanoparticles for preclinical and clinical research; pathological conditions that influence Cu metabolism such as Menkes syndrome, Wilson disease, inflammation, tumor growth, metastasis, angiogenesis, and drug resistance have been studied. We aim to discuss all Cu radioisotopes application focusing on 64Cu and in particular its form 64CuCl2 that seems to be the most promising for its half-life, radiation emissions, and stability with chelators, allowing several applications in oncological and nononcological fields.

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“…In hypoxic cells, the radical is further reduced and then binds to intracellular macromolecules, irreversibly trapping it within the cell (49 (77,78). To our knowledge, there is only one similar study in NPC which was published as an abstract (79).…”

Section: Nitroimidazolesmentioning

confidence: 97%

Clinical significance of hypoxia in nasopharyngeal carcinoma with a focus on existing and novel hypoxia molecular imaging

Yip¹,

Cook

Wee

et al. 2016

Chin. Clin. Oncol.

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Contribution of [64Cu]-ATSM PET in molecular imaging of tumour hypoxia compared to classical [18F]-MISO — a selected review

Abstract: Cu-ATSM appears superior in terms of imaging performance, calling for industrial and clinical development of this innovative radiopharmaceutical.

Cited by 68 publications

References 39 publications

PET/MRI of Hypoxic Atherosclerosis Using ⁶⁴Cu-ATSM in a Rabbit Model

PET/MRI of Hypoxic Atherosclerosis Using ⁶⁴Cu-ATSM in a Rabbit Model

The Copper Radioisotopes: A Systematic Review with Special Interest to⁶⁴Cu

Clinical significance of hypoxia in nasopharyngeal carcinoma with a focus on existing and novel hypoxia molecular imaging

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Contribution of [64Cu]-ATSM PET in molecular imaging of tumour hypoxia compared to classical [18F]-MISO — a selected review

Abstract: Cu-ATSM appears superior in terms of imaging performance, calling for industrial and clinical development of this innovative radiopharmaceutical.

Cited by 68 publications

References 39 publications

PET/MRI of Hypoxic Atherosclerosis Using 64Cu-ATSM in a Rabbit Model

PET/MRI of Hypoxic Atherosclerosis Using 64Cu-ATSM in a Rabbit Model

The Copper Radioisotopes: A Systematic Review with Special Interest to64Cu

Clinical significance of hypoxia in nasopharyngeal carcinoma with a focus on existing and novel hypoxia molecular imaging

Contact Info

Product

Resources

About

PET/MRI of Hypoxic Atherosclerosis Using ⁶⁴Cu-ATSM in a Rabbit Model

PET/MRI of Hypoxic Atherosclerosis Using ⁶⁴Cu-ATSM in a Rabbit Model

The Copper Radioisotopes: A Systematic Review with Special Interest to⁶⁴Cu