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Comparison of the [18F]-FDG and [18F]-FLT PET Tracers in the Evaluation of the Preclinical Proton Therapy Response in Hepatocellular Carcinoma

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Abstract

Purpose

The main objective of the present study was to compare the 2-deoxy-2-[18F]fluoro-D-glucose ([18F]-FDG) and 3′-[18F]fluoro-3′-deoxythymidine ([18F]-FLT) PET imaging biomarkers for the longitudinal follow-up of small animal proton therapy studies in the context of hepatocellular carcinoma (HCC).

Procedures

SK-HEP-1 cells were injected into NMRI nude mice to mimic human HCC. The behavior of [18F]-FDG and [18F]-FLT tumor uptake was evaluated after proton therapy procedures. The proton single-fraction doses were 5, 10, and 20 Gy, with a dose rate of 10 Gy/min. The experimental protocol consisted of 8 groups of 10 mice, each group experiencing a particular dose/radiotracer condition. A reference PET exam was performed on each mouse the day before the irradiation procedure, followed by PET exams every 3 days up to 16 days after irradiation.

Results

[18F]-FDG uptake showed a linear dose-dependent increase in the first days after treatment (37%, p < 0.05), while [18F]-FLT uptake decreased in a dose-dependent manner (e.g., 21% for 5 Gy compared to 10 Gy, p = 1.1e-2). At the later time point, [18F]-FDG normalized activity showed an 85% decrease (p < 0.01) for both 10 and 20 Gy doses and no variation for 5 Gy. Conversely, a significant 61% (p = 0.002) increase was observed for [18F]-FLT normalized activity at 5 Gy and no variation for higher doses.

Conclusion

We showed that the use of the [18F]-FDG and [18F]-FLT radiolabeled molecules can provide useful and complementary information for longitudinal follow-up of small animal proton therapy studies in the context of HCC. [18F]-FDG PET imaging enables a treatment monitoring several days/weeks postirradiation. On the other hand, [18F]-FLT could represent a good candidate to monitor the treatment few days postirradiation, in the context of hypo-fractioned and close irradiation planning. This opens new perspectives in terms of treatment efficacy verification depending on the irradiation scheme.

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Acknowledgements

This work was partly supported by ITMO Cancer AVIESAN (Alliance Nationale pour les Sciences de la Vie et de la Santé, National Alliance for Life Sciences and Health) within the framework of the Cancer Plan and by IN2P3. The authors wish to thank Bruno Jessel, Lionel Thomas, Jacky Schuler, Michel Pellicioli, Julie Constanzo, and Cédric Mathieu for their help in performing all the experiments. We also thank all the members of the mechanical workshop involved in the development of the beam line.

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Authors and Affiliations

  1. Université de Strasbourg, CNRS, IPHC UMR 7178, F-67000, Strasbourg, France

    David Brasse, Patrice Marchand, Marc Rousseau, Ali Ouadi, Marie Vanstalle, Christian Finck, Patrice Laquerriere & Frédéric Boisson

  2. Institut de Cancérologie Strasbourg Europe (ICANS), UNICANCER, Paul Strauss Comprehensive Cancer Center, Radiobiology Laboratory, 67000, Strasbourg, France

    Hélène Burckel

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  1. David Brasse
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Contributions

All authors discussed and conceived the generic concept and reviewed the manuscript. D.B. wrote the main part of the manuscript. P.M. and A.O. contributed to the PET experiments. M.R., M.V. and C.F. participated in the setup of the preclinical proton beam line and the associated dosimetry. H.B. performed the cell culture and the immunohistochemical procedure and analyses. P.L. performed the statistical analyses. F.B and D.B analyzed the PET data.

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Correspondence to David Brasse.

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Brasse, D., Burckel, H., Marchand, P. et al. Comparison of the [18F]-FDG and [18F]-FLT PET Tracers in the Evaluation of the Preclinical Proton Therapy Response in Hepatocellular Carcinoma. Mol Imaging Biol 23, 724–732 (2021). https://doi.org/10.1007/s11307-021-01602-3

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