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Langen B, Rudqvist N, Parris TZ, et al. Transcriptional response in normal mouse tissues after i.v. (211)At administration - response related to absorbed dose, dose rate, and time. EJNMMI Res. 2015;5:1doi: 10.1186/s13550-014-0078-7.
Langen, B., Rudqvist, N., Parris, T. Z., Schüler, E., Spetz, J., Helou, K., & Forssell-Aronsson, E. (2015). Transcriptional response in normal mouse tissues after i.v. (211)At administration - response related to absorbed dose, dose rate, and time. EJNMMI research, 51. https://doi.org/10.1186/s13550-014-0078-7
Langen, Britta, et al. "Transcriptional response in normal mouse tissues after i.v. (211)At administration - response related to absorbed dose, dose rate, and time." EJNMMI research vol. 5 (2015): 1. doi: https://doi.org/10.1186/s13550-014-0078-7
Langen B, Rudqvist N, Parris TZ, Schüler E, Spetz J, Helou K, Forssell-Aronsson E. Transcriptional response in normal mouse tissues after i.v. (211)At administration - response related to absorbed dose, dose rate, and time. EJNMMI Res. 2015 Jan 28;5:1. doi: 10.1186/s13550-014-0078-7. eCollection 2015. PMID: 25853007; PMCID: PMC4384707.
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EJNMMI Res. 2015 Jan 28;5:1. doi: 10.1186/s13550-014-0078-7. eCollection 2015.

Transcriptional response in normal mouse tissues after i.v. (211)At administration - response related to absorbed dose, dose rate, and time.

EJNMMI research

Britta Langen, Nils Rudqvist, Toshima Z Parris, Emil Schüler, Johan Spetz, Khalil Helou, Eva Forssell-Aronsson

Affiliations

  1. Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden ; Department of Applied Physics, Chalmers University of Technology, 412 96 Gothenburg, Sweden.
  2. Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden.
  3. Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden.

PMID: 25853007 PMCID: PMC4384707 DOI: 10.1186/s13550-014-0078-7

Abstract

BACKGROUND: In cancer radiotherapy, knowledge of normal tissue responses and toxicity risks is essential in order to deliver the highest possible absorbed dose to the tumor while maintaining normal tissue exposure at non-critical levels. However, few studies have investigated normal tissue responses in vivo after (211)At administration. In order to identify molecular biomarkers of ionizing radiation exposure, we investigated genome-wide transcriptional responses to (very) low mean absorbed doses from (211)At in normal mouse tissues.

METHODS: Female BALB/c nude mice were intravenously injected with 1.7 kBq (211)At and killed after 1 h, 6 h, or 7 days or injected with 105 or 7.5 kBq and killed after 1 and 6 h, respectively. Controls were mock-treated. Total RNA was extracted from tissue samples of kidney cortex and medulla, liver, lungs, and spleen and subjected to microarray analysis. Enriched biological processes were categorized after cellular function based on Gene Ontology terms.

RESULTS: Responses were tissue-specific with regard to the number of significantly regulated transcripts and associated cellular function. Dose rate effects on transcript regulation were observed with both direct and inverse trends. In several tissues, Angptl4, Per1 and Per2, and Tsc22d3 showed consistent transcript regulation at all exposure conditions.

CONCLUSIONS: This study demonstrated tissue-specific transcriptional responses and distinct dose rate effects after (211)At administration. Transcript regulation of individual genes, as well as cellular responses inferred from enriched transcript data, may serve as biomarkers in vivo. These findings expand the knowledge base on normal tissue responses and may help to evaluate and limit side effects of radionuclide therapy.

Keywords: Astatine-211; Biomarker; Ionizing radiation; Normal tissue response; Radionuclide therapy

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