Dose painting based on tumor uptake of Cu-ATSM and FDG: a comparative study

Malene Martini Clausen, Anders Elias Hansen, Michael Lundemann, Christian Hollensen, Tobias Pommer, Per Munck af Rosenschold, Annemarie Thuri Kristensen, Andreas Kjær, Fintan J. McEvoy, Svend Aage Engelholm

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    Background: Hypoxia and increased glycolytic activity of tumors are associated with poor prognosis. The of this study was to investigate differences in radiotherapy (RT) dose painting based on the uptake of 2-deoxy-2-[18 F]-
    fluorodeoxyglucose (FDG) and the proposed hypoxia tracer, copper(II)diacetyl-bis(N4)-methylsemithiocarbazone (Cu-ATSM) using spontaneous clinical canine tumor models.
    Methods: Positron emission tomography/computed tomography scans of five spontaneous canine sarcomas and carcinomas were obtained; FDG on day 1 and 64Cu-ATSM on day 2 and 3 (approx. 3 and 24 hours pi.). Sub-volumes dose escalation were defined by a threshold-based method for both tracers and five dose escalation levels were in each sub-volume. Volumetric modulated arc therapy plans were optimized based on the dose escalation regions each scan for a total of three dose plans for each dog. The prescription dose for the GTV was 45 Gy (100%) and it was linearly escalated to a maximum of 150%. The correlations between dose painting plans were analyzed with of dose distribution density maps and quality volume histograms (QVH). Correlation between high-dose regions was investigated with Dice correlation coefficients.
    Results: Comparison of dose plans revealed varying degree of correlation between cases. Some cases displayed a separation of high-dose regions in the comparison of FDG vs. 64Cu-ATSM dose plans at both time points. Among the Dice correlation coefficients, the high dose regions showed the lowest degree of agreement, indicating potential benefit of using multiple tracers for dose painting. QVH analysis revealed that FDG-based dose painting plans adequately covered approximately 50% of the hypoxic regions.
    Conclusion: Radiotherapy plans optimized with the current approach for cut-off values and dose region definitions based on FDG, 64Cu-ATSM 3 h and 24 h uptake in canine tumors had different localization of the regional dose escalation levels. This indicates that 64Cu-ATSM at two different time-points and FDG provide different biological information that has to be taken into account when using the dose painting strategy in radiotherapy treatment planning.
    Original languageEnglish
    JournalRadiation Oncology
    Issue number228
    Number of pages8
    Publication statusPublished - 2014

    Bibliographical note

    This is an Open Access article distributed under the terms of the Creative Commons Attribution License


    • Hypoxia
    • Radiotherapy
    • Dose painting
    • Cu-ATSM
    • Positron emission tomography

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