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Dynamic bioluminescence imaging for quantitative tumour burden assessment using IV or IP administration of d-luciferin: effect on intensity, time kinetics and repeatability of photon emission

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Abstract

Introduction

In vivo bioluminescence imaging (BLI) is a promising technique for non-invasive tumour imaging. d-luciferin can be administrated intraperitonealy or intravenously. This will influence its availability and, therefore, the bioluminescent signal. The aim of this study is to compare the repeatability of BLI measurement after IV versus IP administration of d-luciferin and assess the correlation between photon emission and histological cell count both in vitro and in vivo.

Materials and methods

Fluc-positive R1M cells were subcutaneously inoculated in nu/nu mice. Dynamic BLI was performed after IV or IP administration of d-luciferin. Maximal photon emission (PEmax) was calculated. For repeatability assessment, every acquisition was repeated after 4 h and analysed using Bland-Altman method. A second group of animals was serially imaged, alternating IV and IP administration up to 21 days. When mice were killed, PEmax after IV administration was correlated with histological cell number.

Results

The coefficients of repeatability were 80.2% (IV) versus 95.0% (IP). Time-to-peak is shorter, and its variance lower for IV (p < 0.0001). PEmax was 5.6 times higher for IV. A trend was observed towards lower photon emission per cell in larger tumours.

Conclusion

IV administration offers better repeatability and better sensitivity when compared to IP. In larger tumours, multiple factors may contribute to underestimation of tumour burden. It might, therefore, be beneficial to test novel therapeutics on small tumours to enable an accurate evaluation of tumour burden.

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Acknowledgement

Marleen Keyaerts is a Ph. D. fellow of the Research Foundation—Flanders (Belgium; FWO). Tony Lahoutte is a Senior Clinical Investigator of the Research Foundation—Flanders (Belgium; FWO). Karine Breckpot is a postdoctoral fellow of the Research Foundation—Flanders (Belgium; FWO). The research at ICMI is funded by the Interuniversity Attraction Poles Programme—Belgian State—Belgian Science Policy.

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Authors and Affiliations

  1. In Vivo Cellular and Molecular Imaging (ICMI) Laboratory, Vrije Universiteit Brussel (VUB), Brussels, Belgium

    Marleen Keyaerts, Lea Olive Tchouate-Gainkam, Cindy Peleman, Chris Vanhove, Vicky Caveliers, Axel Bossuyt & Tony Lahoutte

  2. Department of Nuclear Medicine, University Hospital Brussels (UZ-Brussel), Laarbeeklaan 101, 1090, Brussels, Belgium

    Marleen Keyaerts, Chris Vanhove, Vicky Caveliers, Axel Bossuyt & Tony Lahoutte

  3. Bio-Imaging lab, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium

    Jacob Verschueren

  4. Department of Haematology and Immunology, Vrije Universiteit Brussel (VUB), Brussels, Belgium

    Tomas J. Bos

  5. Laboratory of Molecular and Cellular Therapy, Department of Physiology and Immunology, Vrije Universiteit Brussel (VUB), Brussels, Belgium

    Karine Breckpot

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  1. Marleen Keyaerts
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Correspondence to Marleen Keyaerts.

Additional information

Marleen Keyaerts is a Ph. D. fellow of the Research Foundation—Flanders (Belgium; FWO).

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Keyaerts, M., Verschueren, J., Bos, T.J. et al. Dynamic bioluminescence imaging for quantitative tumour burden assessment using IV or IP administration of d-luciferin: effect on intensity, time kinetics and repeatability of photon emission. Eur J Nucl Med Mol Imaging 35, 999–1007 (2008). https://doi.org/10.1007/s00259-007-0664-2

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  • DOI: https://doi.org/10.1007/s00259-007-0664-2

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