18F-EF5 PET Is Predictive of Response to Fractionated Radiotherapy in Preclinical Tumor Models
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{"title"=>"18F-EF5 PET is predictive of response to fractionated radiotherapy in preclinical tumor models", "type"=>"journal", "authors"=>[{"first_name"=>"Rehan", "last_name"=>"Ali", "scopus_author_id"=>"56344082100"}, {"first_name"=>"Sandeep", "last_name"=>"Apte", "scopus_author_id"=>"43760994300"}, {"first_name"=>"Marta", "last_name"=>"Vilalta", "scopus_author_id"=>"16041167400"}, {"first_name"=>"Murugesan", "last_name"=>"Subbarayan", "scopus_author_id"=>"6505763292"}, {"first_name"=>"Zheng", "last_name"=>"Miao", "scopus_author_id"=>"34067706900"}, {"first_name"=>"Frederick T.", "last_name"=>"Chin", "scopus_author_id"=>"7005101917"}, {"first_name"=>"Edward E.", "last_name"=>"Graves", "scopus_author_id"=>"7004397938"}], "year"=>2015, "source"=>"PLoS ONE", "identifiers"=>{"isbn"=>"1932-6203", "issn"=>"19326203", "pui"=>"606879424", "sgr"=>"84947205568", "pmid"=>"26431331", "scopus"=>"2-s2.0-84947205568", "doi"=>"10.1371/journal.pone.0139425"}, "id"=>"92d32b13-908e-35fb-8cd7-39886c624cc6", "abstract"=>"We evaluated the relationship between pre-treatment positron emission tomography (PET) using the hypoxic tracer 18F-[2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3- pentafluoropropyl) acetamide] (18F-EF5) and the response of preclinical tumor models to a range of fractionated radiotherapies. Subcutaneous HT29, A549 and RKO tumors grown in nude mice were imaged using 18F-EF5 positron emission tomography (PET) in order to characterize the extent and heterogeneity of hypoxia in these systems. Based on these results, 80 A549 tumors were subsequently grown and imaged using 18F-EF5 PET, and then treated with one, two, or four fraction radiation treatments to a total dose of 10-40 Gy. Response was monitored by serial caliper measurements of tumor volume. Longitudinal post-treatment 18F-EF5 PET imaging was performed on a subset of tumors. Terminal histologic analysis was performed to validate 18F-EF5 PET measures of hypoxia. EF5-positive tumors responded more poorly to low dose single fraction irradiation relative to EF5-negative tumors, however both groups responded similarly to larger single fraction doses. Irradiated tumors exhibited reduced 18F-EF5 uptake one month after treatment compared to control tumors. These findings indicate that pre- treatment 18F-EF5 PET can predict the response of tumors to single fraction radiation treatment. However, increasing the number of fractions delivered abrogates the difference in response between tumors with high and low EF5 uptake pre-treatment, in agreement with traditional radiobiology.", "link"=>"http://www.mendeley.com/research/18fef5-pet-predictive-response-fractionated-radiotherapy-preclinical-tumor-models", "reader_count"=>13, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>5, "Student > Master"=>2, "Other"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Professor > Associate Professor"=>1, "Student > Doctoral Student"=>1, "Researcher"=>2, "Student > Ph. D. Student"=>5, "Student > Master"=>2, "Other"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Engineering"=>1, "Biochemistry, Genetics and Molecular Biology"=>1, "Agricultural and Biological Sciences"=>1, "Medicine and Dentistry"=>5, "Neuroscience"=>1, "Physics and Astronomy"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Neuroscience"=>{"Neuroscience"=>1}, "Physics and Astronomy"=>{"Physics and Astronomy"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>1}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"Netherlands"=>1, "United States"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/2297125"], "description"=>"<p>Volumes are normalized to pre-treatment volumes.</p>", "links"=>[], "tags"=>["Preclinical Tumor Models", "fraction irradiation", "fraction radiation treatment", "549 tumors", "tumor volume", "terminal histologic analysis", "Fractionated Radiotherapy", "ht", "tumor models", "control tumors", "ef", "RKO tumors", "fraction doses", "fraction radiation treatments", "response", "caliper measurements", "Irradiated tumors"], "article_id"=>1562961, "categories"=>["Biological Sciences"], "users"=>["Rehan Ali", "Sandeep Apte", "Marta Vilalta", "Murugesan Subbarayan", "Zheng Miao", "Frederick T. Chin", "Edward E. Graves"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0139425.g003", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Plots_of_response_of_more_and_less_hypoxic_tumors_to_A_single_fraction_and_B_multiple_fraction_treatments_/1562961", "title"=>"Plots of response of more and less hypoxic tumors to (A) single fraction and (B) multiple fraction treatments.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-02 03:25:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/2297128"], "description"=>"<p>(A) Representative axial <sup>18</sup>F-EF5 PET images of two tumors at 1 day pre-treatment and 13 / 32 days post-treatment. Solid arrow denotes unirradiated control tumor, and dashed arrow denotes tumor which was treated with 20 Gy. (B,C) Plots showing changes in <sup>18</sup>F-EF5 uptake and volume, respectively, in control (n = 6) and irradiated (n = 6) tumors during the treatment timecourse.</p>", "links"=>[], "tags"=>["Preclinical Tumor Models", "fraction irradiation", "fraction radiation treatment", "549 tumors", "tumor volume", "terminal histologic analysis", "Fractionated Radiotherapy", "ht", "tumor models", "control tumors", "ef", "RKO tumors", "fraction doses", "fraction radiation treatments", "response", "caliper measurements", "Irradiated tumors"], "article_id"=>1562964, "categories"=>["Biological Sciences"], "users"=>["Rehan Ali", "Sandeep Apte", "Marta Vilalta", "Murugesan Subbarayan", "Zheng Miao", "Frederick T. Chin", "Edward E. Graves"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0139425.g004", "stats"=>{"downloads"=>0, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effect_of_radiation_on_tumor_18_F_EF5_uptake_/1562964", "title"=>"Effect of radiation on tumor <sup>18</sup>F-EF5 uptake.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-02 03:25:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/2297129"], "description"=>"<p>Values of n/a are reported for growth curves that were flat or decreasing over time.</p>", "links"=>[], "tags"=>["Preclinical Tumor Models", "fraction irradiation", "fraction radiation treatment", "549 tumors", "tumor volume", "terminal histologic analysis", "Fractionated Radiotherapy", "ht", "tumor models", "control tumors", "ef", "RKO tumors", "fraction doses", "fraction radiation treatments", "response", "caliper measurements", "Irradiated tumors"], "article_id"=>1562965, "categories"=>["Biological Sciences"], "users"=>["Rehan Ali", "Sandeep Apte", "Marta Vilalta", "Murugesan Subbarayan", "Zheng Miao", "Frederick T. Chin", "Edward E. Graves"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0139425.t001", "stats"=>{"downloads"=>0, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Doubling_Times_DT_and_Root_Mean_Squared_Deviation_RMSD_between_EF5_positive_and_EF5_negative_tumor_time_curves_for_pre_treatment_and_post_treatment_A549_subcutaneous_tumors_/1562965", "title"=>"Doubling Times (DT) and Root Mean Squared Deviation (RMSD) between EF5 positive and EF5 negative tumor time curves for pre-treatment and post-treatment A549 subcutaneous tumors.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2015-10-02 03:25:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/2297133", "https://ndownloader.figshare.com/files/2297134", "https://ndownloader.figshare.com/files/2297135", "https://ndownloader.figshare.com/files/2297136", "https://ndownloader.figshare.com/files/2297137"], "description"=>"<div><p>We evaluated the relationship between pre-treatment positron emission tomography (PET) using the hypoxic tracer <sup>18</sup>F-[2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3- pentafluoropropyl) acetamide] (<sup>18</sup>F-EF5) and the response of preclinical tumor models to a range of fractionated radiotherapies. Subcutaneous HT29, A549 and RKO tumors grown in nude mice were imaged using <sup>18</sup>F-EF5 positron emission tomography (PET) in order to characterize the extent and heterogeneity of hypoxia in these systems. Based on these results, 80 A549 tumors were subsequently grown and imaged using <sup>18</sup>F-EF5 PET, and then treated with one, two, or four fraction radiation treatments to a total dose of 10–40 Gy. Response was monitored by serial caliper measurements of tumor volume. Longitudinal post-treatment <sup>18</sup>F-EF5 PET imaging was performed on a subset of tumors. Terminal histologic analysis was performed to validate <sup>18</sup>F-EF5 PET measures of hypoxia. EF5-positive tumors responded more poorly to low dose single fraction irradiation relative to EF5-negative tumors, however both groups responded similarly to larger single fraction doses. Irradiated tumors exhibited reduced <sup>18</sup>F-EF5 uptake one month after treatment compared to control tumors. These findings indicate that pre- treatment <sup>18</sup>F-EF5 PET can predict the response of tumors to single fraction radiation treatment. However, increasing the number of fractions delivered abrogates the difference in response between tumors with high and low EF5 uptake pre-treatment, in agreement with traditional radiobiology.</p></div>", "links"=>[], "tags"=>["Preclinical Tumor Models", "fraction irradiation", "fraction radiation treatment", "549 tumors", "tumor volume", "terminal histologic analysis", "Fractionated Radiotherapy", "ht", "tumor models", "control tumors", "ef", "RKO tumors", "fraction doses", "fraction radiation treatments", "response", "caliper measurements", "Irradiated tumors"], "article_id"=>1562969, "categories"=>["Biological Sciences"], "users"=>["Rehan Ali", "Sandeep Apte", "Marta Vilalta", "Murugesan Subbarayan", "Zheng Miao", "Frederick T. Chin", "Edward E. Graves"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0139425.s001", "https://dx.doi.org/10.1371/journal.pone.0139425.s002", "https://dx.doi.org/10.1371/journal.pone.0139425.s003", "https://dx.doi.org/10.1371/journal.pone.0139425.s004", "https://dx.doi.org/10.1371/journal.pone.0139425.s005"], "stats"=>{"downloads"=>6, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_18_F_EF5_PET_Is_Predictive_of_Response_to_Fractionated_Radiotherapy_in_Preclinical_Tumor_Models/1562969", "title"=>"<sup>18</sup>F-EF5 PET Is Predictive of Response to Fractionated Radiotherapy in Preclinical Tumor Models", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-10-02 03:25:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/2297122"], "description"=>"<p>(A) Representative axial slices from microCT (top row), <sup>18</sup>F-EF5 microPET (middle row), and anti-EF5 immunohistochemistry on (bottom row) of HT29, A549 and RKO subcutaneous tumors. CT image intensities represent Hounsfield Units (HU). PET images have been normalized by the mean background muscle %ID/g to yield tumor/muscle ratio (T/M) images. T on microCT and microPET images denotes tumor location. Brown stained areas in IHC images denote regions of bound EF5. (B) Scatterplot of the distribution of <sup>18</sup>F-EF5 uptake in individual HT29, A549 and RKO subcutaneous tumors using three different metrics, T/M measured using CT-derived ROIs (T/MCT), T/M measured using PET-derived ROIs (T/MPET) and %ID/g values measured using CT-derived ROIs (%ID/gCT). (C) Scatterplot of the relationship between T/MCT for HT29, A549 and RKO tumors and their volume.</p>", "links"=>[], "tags"=>["Preclinical Tumor Models", "fraction irradiation", "fraction radiation treatment", "549 tumors", "tumor volume", "terminal histologic analysis", "Fractionated Radiotherapy", "ht", "tumor models", "control tumors", "ef", "RKO tumors", "fraction doses", "fraction radiation treatments", "response", "caliper measurements", "Irradiated tumors"], "article_id"=>1562958, "categories"=>["Biological Sciences"], "users"=>["Rehan Ali", "Sandeep Apte", "Marta Vilalta", "Murugesan Subbarayan", "Zheng Miao", "Frederick T. Chin", "Edward E. Graves"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0139425.g001", "stats"=>{"downloads"=>2, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_Representative_axial_slices_from_microCT_top_row_18_F_EF5_microPET_middle_row_and_anti_EF5_immunohistochemistry_on_bottom_row_of_HT29_A549_and_RKO_subcutaneous_tumors_CT_image_intensities_represent_Hounsfield_Units_HU_PET_images_have_been_normalized_by/1562958", "title"=>"(A) Representative axial slices from microCT (top row), <sup>18</sup>F-EF5 microPET (middle row), and anti-EF5 immunohistochemistry on (bottom row) of HT29, A549 and RKO subcutaneous tumors. CT image intensities represent Hounsfield Units (HU). PET images have been normalized by the mean background muscle %ID/g to yield tumor/muscle ratio (T/M) images. T on microCT and microPET images denotes tumor location. Brown stained areas in IHC images denote regions of bound EF5. (B) Scatterplot of the distribution of <sup>18</sup>F-EF5 uptake in individual HT29, A549 and RKO subcutaneous tumors using three different metrics, T/M measured using CT-derived ROIs (T/MCT), T/M measured using PET-derived ROIs (T/MPET) and %ID/g values measured using CT-derived ROIs (%ID/gCT). (C) Scatterplot of the relationship between T/MCT for HT29, A549 and RKO tumors and their volume.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-02 03:25:22"}
  • {"files"=>["https://ndownloader.figshare.com/files/2297123"], "description"=>"<p>The gray region denotes EF5 negative tumors (defined as T/MPET < 2.5), and the red region denotes EF5 positive tumors (T/MPET > 2.5).</p>", "links"=>[], "tags"=>["Preclinical Tumor Models", "fraction irradiation", "fraction radiation treatment", "549 tumors", "tumor volume", "terminal histologic analysis", "Fractionated Radiotherapy", "ht", "tumor models", "control tumors", "ef", "RKO tumors", "fraction doses", "fraction radiation treatments", "response", "caliper measurements", "Irradiated tumors"], "article_id"=>1562959, "categories"=>["Biological Sciences"], "users"=>["Rehan Ali", "Sandeep Apte", "Marta Vilalta", "Murugesan Subbarayan", "Zheng Miao", "Frederick T. Chin", "Edward E. Graves"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0139425.g002", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_A_Scatterplot_of_the_relationship_between_18_F_EF5_T_M_values_for_individual_tumors_when_quantified_using_either_PET_and_CT_derived_ROIs_T_MPET_and_T_MCT_respectively_with_a_linear_regression_line_superimposed_The_four_quadrants_represent_regions_where_b/1562959", "title"=>"(A) Scatterplot of the relationship between <sup>18</sup>F-EF5 T/M values for individual tumors when quantified using either PET and CT derived ROIs (T/MPET and T/MCT respectively), with a linear regression line superimposed. The four quadrants represent regions where both T/MPET and T/MCT are below the designated hypoxia threshold (EF5 -), or both are above the threshold (EF5 +), or only one is above the threshold (EF5CT+/EF5PET- or EF5CT-/EF5PET+). (B) Scatterplot of <sup>18</sup>F-EF5 tumor uptake vs tumor volume.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2015-10-02 03:25:22"}

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Relative Metric

{"start_date"=>"2015-01-01T00:00:00Z", "end_date"=>"2015-12-31T00:00:00Z", "subject_areas"=>[]}
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