Assessing tumor hypoxia by positron emission tomography with Cu-ATSM

Radiochemistry Service, Department of Radiology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
The quarterly journal of nuclear medicine and molecular imaging: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of... (Impact Factor: 2.03). 07/2009; 53(2):193-200.
Source: PubMed


For the last several decades, hypoxia has been recognized to be one of the key factors in tumor aggression and an important impediment to local and distant control of malignant tumors. In addition, hypoxia is a major cause of failure of both radiation therapy and chemotherapy. It has been shown that hypoxia is an independent negative prognostic factor for patient outcome in various solid tumors. Clinical studies using polarographic oxygen electrodes, as a tool for measuring hypoxia, were the first to demonstrate the presence of hypoxia in human tumors and its association with poor prognosis. However, this method is invasive and has technical limitations that prevent its routine clinical use. Over the years, imaging as a noninvasive method has attracted a lot of attention and several radiotracers have been developed for noninvasive evaluation of hypoxia. One of the most promising radiotracers is the copper(II) complex of diacetyl-2,3-bis(N(4)-methyl-3-thiosemicarbazonato) ligand (Cu-ATSM) for imaging with positron emission tomography. In this review, the preclinical evaluation of Cu-ATSM as well as its clinical value in several solid tumors will be discussed.

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    • "The proposed trapping mechanism of Cu-ATSM is indirectly linked to hypoxia, via chemical reduction from a cell membrane permeable to a non-permeable state. The exact mechanism by which Cu-ATSM is trapped in hypoxic cells or the oxygen-level required for accumulation is however not completely understood [7,8]. "
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    ABSTRACT: The aim of this study was to compare (64)Cu-diacetyl-bis(N(4)-methylsemicarbazone) ((64)Cu-ATSM) and (18)FDG PET uptake characteristics and (64)Cu-ATSM autoradiography to pimonidazole immunohistochemistry in spontaneous canine sarcomas and carcinomas. Biopsies were collected from individual tumors between approximately 3 and 25 hours after the intravenous injection of (64)Cu-ATSM and pimonidazole. (64)Cu-ATSM autoradiography and pimonidazole immunostaining was performed on sectioned biopsies. Acquired (64)Cu-ATSM autoradiography and pimonidazole images were rescaled, aligned and their distribution patterns compared. (64)Cu-ATSM and (18)FDG PET/CT scans were performed in a concurrent study and uptake characteristics were obtained for tumors where available. Maximum pimonidazole pixel value and mean pimonidazole labeled fraction was found to be strongly correlated to (18)FDG PET uptake levels, whereas more varying results were obtained for the comparison to (64)Cu-ATSM. In the case of the latter, uptake at scans performed 3 h post injection (pi) generally showed strong positive correlated to pimonidazole uptake.Comparison of distribution patterns of pimonidazole immunohistochemistry and (64)Cu-ATSM autoradiography yielded varying results. Significant positive correlations were mainly found in sections displaying a heterogeneous distribution of tracers. Tumors with high levels of pimonidazole staining generally displayed high uptake of (18)FDG and (64)Cu-ATSM (3 h pi.). Similar regional distribution of (64)Cu-ATSM and pimonidazole was observed in most heterogeneous tumor regions. However, tumor and hypoxia level dependent differences may exist with regard to the hypoxia specificity of (64)Cu-ATSM in canine tumors.
    Radiation Oncology 06/2012; 7(1):89. DOI:10.1186/1748-717X-7-89 · 2.55 Impact Factor
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    01/2010; Springer.
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    ABSTRACT: Hypoxia plays a critical role in tumor development and aggressiveness and is an important prognostic factor for resistance to antineoplastic treatments; therefore, it is required to measure the hypoxic level of tumor for a favorable outcome. The pretherapy information on the oxygenation status of a tumor microenvironment should also have implications for treatment selection. A diffuse distribution of hypoxia in a tumor might suggest a benefit from a systemic approach, such as a hypoxic cell cytotoxin, tirapazamine, or antigrowth factor drugs to combat the limitations of hypoxia. Alternatively, a more focal hypoxia might benefit from a local/regional approach, such as intensity-modulated radiation therapy-based radiation dose escalation to the hypoxic subvolume. This review anticipates that (18)F-FMISO ((18)F-fluoromisonodazole) and (64)Cu-ATSM-positron emission tomography (PET) will prove useful for selecting individual patients for the most appropriate treatment. The advent of new radiotracers has allowed noninvasive assessment of hypoxia, with the most extensively investigated and validated PET radiotracer for hypoxia to date being (18)F-FMISO. This article discusses the relevance and biology of hypoxia in cells and organ systems and reviews the laboratory and clinical applications of (18)F-FMISO and other agents in oncology.
    Cancer Biotherapy & Radiopharmaceuticals 06/2010; 25(3):365-74. DOI:10.1089/cbr.2009.0740 · 1.78 Impact Factor
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