Re: Devic et al. (Int J Radiat Oncol Biol Phys 2010;78:1555–1562)

International journal of radiation oncology, biology, physics (Impact Factor: 4.26). 11/2011; 81(3):902; author reply 902-3. DOI: 10.1016/j.ijrobp.2011.05.020
Source: PubMed
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    ABSTRACT: We discuss the effect of (18)F-fluoro-deoxy-glucose (FDG) positron emission tomography (PET)/computed tomography (CT) data on target volume definition for radiotherapy planning. We compared the effect of various thresholding methods on the PET-based target volume vs. the standard CT-based tumor volume. Different thresholding methods were reviewed and compared to our PET-based gross tumor volume data obtained from a cohort of 31 non-small-cell lung carcinoma patients who had undergone preoperative PET/CT scans for staging. The feasibility and limitations of FDG-based PET/CT data on target volume delineation in radiotherapy planning have been demonstrated with frequently used approaches for target outlining such as the qualitative visual method and the fixed 15% or 40% of the maximal iso-uptake value threshold methods. The relationship between PET-based and CT-based volumes generally suffers from poor correlation between the two image data sets, expressed in terms of a large statistical variation in gross tumor volume ratios, irrespective of the threshold method used. However, we found that the maximal signal/background ratios in non-small-cell lung carcinoma patients correlated well with the pathologic results, with an average ratio for adenocarcinoma, large cell carcinoma, and squamous cell carcinoma of 10.5 ± 3.5, 12.6 ± 2.8, and 14.1 ± 5.9, respectively. The fluctuations in tumor volume using different quantitative PET thresholding approaches did not depend on the thresholding method used. They originated from the nature of functional imaging in general and PET imaging in particular. Functional imaging will eventually be used for biologically tailored target radiotherapy volume definition not as a replacement of CT- or magnetic resonance imaging-based anatomic gross tumor volumes but with the methods complementing each other in a complex mosaic of distinct biologic target volumes.
    International journal of radiation oncology, biology, physics 12/2010; 78(5):1555-62. DOI:10.1016/j.ijrobp.2010.02.015 · 4.26 Impact Factor
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    ABSTRACT: Apoptosis is a genetically encoded programme of cell death that can be activated under physiological conditions and may be an important safeguard against tumour development. Regions of low oxygen (hypoxia) and necrosis are common features of solid tumours. Here we report that hypoxia induces apoptosis in oncogenically transformed cells and that further genetic alterations, such as loss of the p53 tumour-suppressor gene or overexpression of the apoptosis-inhibitor protein Bcl-2, substantially reduce hypoxia-induced cell death. Hypoxia also selects for cells with defects in apoptosis, because small numbers of transformed cells lacking p53 overtake similar cells expressing wild-type p53 when treated with hypoxia. Furthermore, highly apoptotic regions strongly correlate with hypoxic regions in transplanted tumours expressing wild-type p53, whereas little apoptosis occurs in hypoxic regions of p53-deficient tumours. We propose that hypoxia provides a physiological selective pressure in tumours for the expansion of variants that have lost their apoptotic potential, and in particular for cells acquiring p53 mutations.
    Nature 02/1996; 379(6560):88-91. DOI:10.1038/379088a0 · 41.46 Impact Factor
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    ABSTRACT: The primary purpose of this study was to assess the biodistribution and radiation dose resulting from administration of (18)F-EF5, a lipophilic 2-nitroimidazole hypoxia marker in ten cancer patients. For three of these patients (with glioblastoma) unlabeled EF5 was additionally administered to allow the comparative assessment of (18)F-EF5 tumor uptake with EF5 binding, the latter measured in tumor biopsies by fluorescent anti-EF5 monoclonal antibodies. (18)F-EF5 was synthesized by electrophilic addition of (18)F(2) gas, made by deuteron bombardment of a neon/fluorine mixture in a high-pressure gas target, to an allyl precursor in trifluoroacetic acid at 0° then purified and administered by intravenous bolus. Three whole-body images were collected for each of ten patients using an Allegro (Philips) scanner. Gamma counts were determined in blood, drawn during each image, and urine, pooled as a single sample. PET images were analyzed to determine radiotracer uptake in several tissues and the resulting radiation dose calculated using OLINDA software and standard phantom. For three patients, 21 mg/kg unlabeled EF5 was administered after the PET scans, and tissue samples obtained the next day at surgery to determine EF5 binding using immunohistochemistry techniques (IHC). EF5 distributes evenly throughout soft tissue within minutes of injection. Its concentration in blood over the typical time frame of the study (∼3.5 h) was nearly constant, consistent with a previously determined EF5 plasma half-life of ∼13 h. Elimination was primarily via urine and bile. Radiation exposure from labeled EF5 is similar to other (18)F-labeled imaging agents (e.g., FDG and FMISO). In a de novo glioblastoma multiforme patient, focal uptake of (18)F-EF5 was confirmed by IHC. These results confirm predictions of biodistribution and safety based on EF5's characteristics (high biological stability, high lipophilicity). EF5 is a novel hypoxia marker with unique pharmacological characteristics allowing both noninvasive and invasive measurements.
    European Journal of Nuclear Medicine 11/2010; 37(11):2048-59. DOI:10.1007/s00259-010-1517-y · 5.38 Impact Factor
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