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Dose-Dependent Uptake of 3′-deoxy-3′-[18 F]Fluorothymidine by the Bowel after Total-Body Irradiation

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Abstract

Purpose

The aim of this study is to non-invasively assess early, irradiation-induced normal tissue alterations via metabolic imaging with 3′-deoxy-3′-[18 F]fluorothymidine ([18 F]FLT).

Procedures

Twenty-nine male C57BL/6 mice were investigated by [18 F]FLT positron emission tomography for 7 days after total body irradiation (1, 4, and 8 Gy) versus ‘sham’ irradiation (0 Gy). Target/background ratios were determined. The imaging results were validated by histology and immunohistochemistry (Thymidine kinase 1, Ki-67).

Results

[18 F]FLT demonstrated a dose-dependent intestinal accumulation post irradiation. Mean target/background ratio (±standard error) 0 Gy: 1.4 (0.2), 1 Gy: 1.7 (0.1), 4 Gy: 3.1 (0.3), 8 Gy: 4.2 (0.6). Receiver operating characteristic analysis (area under the curve, p value): 0 vs. 1 Gy: 0.81, 0.049; 0 vs. 4 Gy: 1.0, 0.0016; and 0 vs. 8 Gy: 1.0, 0.0020. Immunohistochemistry confirmed the results.

Conclusions

[18 F]FLT seems to provide dose-dependent information on radiation-induced proliferation in the bowel. This opens the perspective for monitoring therapy-related side-effects as well as assessing, e.g., radiation accident victims.

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Acknowledgments

We are indebted to Heidrun Zankl, Stefan Zothe, Claudia Schlosser, and Andreas Hartenbach for their support and Wolfgang Dörr (Department of Radiation Oncology, Medical University Vienna) for the critical revision of the manuscript.

Funding

This study was funded by the German Ministry of Defense (BMVg) code: M_SAB X_BA002. Sabrina Niedermoser and Andreas Delker report personal fees from this funding.

Conflict of Interest

All other authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Armed Forces Hospital, Oberer Eselsberg 40, 89081, Ulm, Germany

    Markus Hartenbach

  2. Department of Nuclear Medicine, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany

    Andreas Delker, Juli Schlichtiger, Sabrina Niedermoser, Carmen Wängler, Björn Wängler, Guido Böning, Franz Josef Gildehaus & Peter Bartenstein

  3. Department of Pathology, Armed Forces Hospital, Oberer Eselsberg 40, 89081, Ulm, Germany

    Sabrina Hartenbach & Klaus Kraft

  4. Clinic for Radiotherapy and Radiation Oncology, University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany

    Klement Neumaier, Kirsten Lauber & Claus Belka

  5. Division of Nuclear Medicine, Department of Radiology, MUW, Währinger Gürtel 18-20, Floor 5L, 1090, Vienna, Austria

    Markus Hartenbach & Marcus Hacker

  6. Armed Forces Institute of Radiobiology, Neuherbergstraße 11, 80937, Munich, Germany

    Viktor Meineke

  7. Molecular Imaging and Radiochemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany

    Sabrina Niedermoser & Björn Wängler

  8. Biomedical Chemistry, Department of Clinical Radiology and Nuclear Medicine, Medical Faculty Mannheim of Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany

    Carmen Wängler

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  1. Markus Hartenbach
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  2. Andreas Delker
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Correspondence to Markus Hartenbach.

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Hartenbach, M., Delker, A., Hartenbach, S. et al. Dose-Dependent Uptake of 3′-deoxy-3′-[18 F]Fluorothymidine by the Bowel after Total-Body Irradiation. Mol Imaging Biol 16, 846–853 (2014). https://doi.org/10.1007/s11307-014-0755-y

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