title: Transcriptional Response in Mouse Thyroid Tissue after 211At Administration: Effects of Absorbed Dose, Initial Dose-Rate and Time after Administration.
abstract: BACKGROUND
  211At-labeled radiopharmaceuticals are potentially useful for tumor therapy. However, a limitation has been the preferential accumulation of released 211At in the thyroid gland, which is a critical organ for such therapy. The aim of this study was to determine the effect of absorbed dose, dose-rate, and time after 211At exposure on genome-wide transcriptional expression in mouse thyroid gland.
  
  
  METHODS
  BALB/c mice were i.v. injected with 1.7, 7.5 or 100 kBq 211At. Animals injected with 1.7 kBq were killed after 1, 6, or 168 h with mean thyroid absorbed doses of 0.023, 0.32, and 1.8 Gy, respectively. Animals injected with 7.5 and 100 kBq were killed after 6 and 1 h, respectively; mean thyroid absorbed dose was 1.4 Gy. Total RNA was extracted from pooled thyroids and the Illumina RNA microarray platform was used to determine mRNA levels. Differentially expressed transcripts and enriched GO terms were determined with adjusted p-value <0.01 and fold change >1.5, and p-value <0.05, respectively.
  
  
  RESULTS
  In total, 1232 differentially expressed transcripts were detected after 211At administration, demonstrating a profound effect on gene regulation. The number of regulated transcripts increased with higher initial dose-rate/absorbed dose at 1 or 6 h. However, the number of regulated transcripts decreased with mean absorbed dose/time after 1.7 kBq 211At administration. Furthermore, similar regulation profiles were seen for groups administered 1.7 kBq. Interestingly, few previously proposed radiation responsive genes were detected in the present study. Regulation of immunological processes were prevalent at 1, 6, and 168 h after 1.7 kBq administration (0.023, 0.32, 1.8 Gy).
authors.affiliation: Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Nils
authors.initials: N
authors.lastname: Rudqvist
authors.affiliation: Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Spetz
authors.affiliation: Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Emil
authors.initials: E
authors.lastname: Schüler
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Toshima Z
authors.initials: TZ
authors.lastname: Parris
authors.affiliation: Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Britta
authors.initials: B
authors.lastname: Langen
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Khalil
authors.initials: K
authors.lastname: Helou
authors.affiliation: Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Forssell-Aronsson
mesh_terms: D000818:Animals; D001246:Astatine / Q000737:chemistry; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005786:Gene Expression Regulation / Q000528:radiation effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000302:isolation & purification / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000008:administration & dosage* / Q000737:chemistry; D013961:Thyroid Gland / Q000378:metabolism*; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; D019275:Radiopharmaceuticals; D012313:RNA; D001246:Astatine