Transcriptional response in normal mouse tissues after i.v. 211At administration - response related to absorbed dose, dose rate, and time
Journal article, 2015

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 211At administration. In order to identify molecular biomarkers of ionizing radiation exposure, we investigated genome-wide transcriptional responses to (very) low mean absorbed doses from 211At in normal mouse tissues. Methods Female BALB/c nude mice were intravenously injected with 1.7 kBq 211At 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 211At 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; Ionizing radiation; Normal tissue response; Radionuclide therapy; Biomarke

Ionizing radiation

Radionuclide therapy

Astatine-211

Biomarker

Normal tissue response

Author

Britta Langen

Chalmers, Applied Physics, Nuclear Engineering

University of Gothenburg

Nils Rudqvist

University of Gothenburg

Toshima Z Parris

University of Gothenburg

Emil Schüler

University of Gothenburg

Johan Spetz

University of Gothenburg

Khalil Helou

University of Gothenburg

Eva Forssell-Aronsson

University of Gothenburg

EJNMMI Research

2191219x (eISSN)

Vol. 5 1 1-12 1

Subject Categories

Biochemistry and Molecular Biology

Cell and Molecular Biology

Radiology, Nuclear Medicine and Medical Imaging

Cancer and Oncology

DOI

10.1186/s13550-014-0078-7

PubMed

25853007

More information

Latest update

4/5/2022 7