N. Importantly, the muscle clearance was not affected by the different
N. Importantly, the muscle clearance was not affected by the different oxygen breathing conditions while the tumor clearance was lower when mice were breathing air. Conclusion: Exogenous CT26 colon carcinomas and endogenous polyoma middle-T (PyV-mT) mammary carcinomas showed no differences in [18F]FAZA uptake 1-3 h p.i. Our analysis using various breathing protocols with air (P0) and with pure oxygen (P1, P2) clearly indicate that [18F]FAZA is an appropriate PET biomarker for in vivo analysis of hypoxia revealing an enhanced tracer uptake in tumors with reduced oxygen supply. [18F]FAZA uptake was independent of tumor-type.* Correspondence: [email protected] Contributed equally 1 Department of Preclinical Imaging and Radiopharmacy, Laboratory for Preclinical Imaging and Imaging Technology of the Werner SiemensFoundation, University of T ingen, Germany Full list of author information is available at the end of the article?2011 Maier et al; licensee BioMed Central Ltd. This is an Open Access article Pemafibrate web distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Maier et al. Radiation Oncology 2011, 6:165 http://www.ro-journal.com/content/6/1/Page 2 ofIntroduction Tumor hypoxia, one of the major hallmarks of malignant tumor disease, is indicative of more aggressive tumor progression and is associated with angiogenesis and metastasis [1-4]. Hypoxic tumor PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28499442 tissue is also known to be more resistant to radiotherapy and chemotherapy compared to normally oxygenated tumor tissue [1]. Identifying and targeting the hypoxic areas of tumors is pivotal for selecting patients who require additional or more specific treatment strategies. Several invasive and noninvasive techniques are currently available, although oxygen electrode systems for detecting hypoxia are not clinically used due to their invasiveness and limitations concerning the accessibility of the tumor [5,6]. However, noninvasive in vivo identification and quantification of hypoxic tumor regions using positron emission tomography (PET) is a field of growing interest and has been investigated in recent years [7,8]. Currently, a variety of PET tracers are available for hypoxia imaging, such as [18F]fluoromisonidazole ([18F]FMISO) [9-13], [18F]FAZA [14-16], [124I]-iodo-azomycinarabinofuranoside ([124I]IAZA) [17,18] and [64Cu]-(II)diacetylbis(N4-methylthiosemicarbazone) ([ 64 Cu]ATSM) [19-21]. The 2-Nitroimidazole tracers show selective uptake in hypoxic cells both in vitro and in vivo. In contrast [64Cu]ATSM binding may also involve mechanisms independent of hypoxia [22]. In line with this Yuan et al. have recently reported that [64Cu]ATSM is a valid hypoxia marker for some tumors but not for all as enhanced tracer uptake was found also in areas without any hypoxia but with enhanced perfusion [23]. However, for reliable use of 2-Nitroimidazole tracers in clinical settings, further evaluation studies are needed. [ 18 F]FAZA and [ 18 F]FMISO are currently two of the PET biomarkers with great promise for imaging tumor hypoxia [24] and have been the focus of clinical studies. 2-Nitroimidazole tracers such as [18F]FAZA are readily diffusible through cell membranes and undergo reversible reduction by intracellular reductases to yield nitroimidazole radical anions, which are then rapidly reoxidized to neutral.