title: 18F-EF5 PET Is Predictive of Response to Fractionated Radiotherapy in Preclinical Tumor Models.
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.
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, CA, United States of America.
authors.forename: Rehan
authors.initials: R
authors.lastname: Ali
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, CA, United States of America.
authors.forename: Sandeep
authors.initials: S
authors.lastname: Apte
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, CA, United States of America.
authors.forename: Marta
authors.initials: M
authors.lastname: Vilalta
authors.affiliation: Department of Radiology, Stanford University, Stanford, CA, United States of America.
authors.forename: Murugesan
authors.initials: M
authors.lastname: Subbarayan
authors.affiliation: Department of Radiology, Stanford University, Stanford, CA, United States of America.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Miao
authors.affiliation: Department of Radiology, Stanford University, Stanford, CA, United States of America.
authors.forename: Frederick T
authors.initials: FT
authors.lastname: Chin
authors.affiliation: Department of Radiation Oncology, Stanford University, Stanford, CA, United States of America.
authors.forename: Edward E
authors.initials: EE
authors.lastname: Graves
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000532:radiotherapy; D000818:Animals; D002277:Carcinoma / Q000000981:diagnostic imaging / Q000532:radiotherapy; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D019583:Dose Fractionation, Radiation; D017341:Etanidazole / Q000031:analogs & derivatives / Q000032:analysis; D005462:Fluorine Radioisotopes / Q000032:analysis; D064593:Heterografts; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000032:analysis; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D049268:Positron-Emission Tomography / Q000379:methods*; D011879:Radiotherapy Dosage; D040521:Subcutaneous Tissue; D047368:Tumor Burden; D005466:Fluorocarbons
chemical_list: D017341:Etanidazole; D005462:Fluorine Radioisotopes; D006845:Hydrocarbons, Fluorinated; C096011:2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide; D005466:Fluorocarbons