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Investigation of cis-4-[18F]Fluoro-D-Proline Uptake in Human Brain Tumors After Multimodal Treatment

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Abstract

Purpose

Cis-4-[18F]fluoro-D-proline (D-cis-[18F]FPro) has been shown to pass the intact blood-brain barrier and to accumulate in areas of secondary neurodegeneration and necrosis in the rat brain while uptake in experimental brain tumors is low. This pilot study explores the uptake behavior of D-cis-[18F]FPro in human brain tumors after multimodal treatment.

Procedures

In a prospective study, 27 patients with suspected recurrent brain tumor after treatment with surgery, radiotherapy, and/or chemotherapy (SRC) were investigated by dynamic positron emission tomography (PET) using D-cis-[18F]FPro (22 high-grade gliomas, one unspecified glioma, and 4 metastases). Furthermore, two patients with untreated lesions were included (one glioblastoma, one reactive astrogliosis). Data were compared with the results of PET using O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) which detects viable tumor tissue. Tracer distribution, mean and maximum lesion-to-brain ratios (LBRmean, LBRmax), and time-to-peak (TTP) of the time activity curve (TAC) of tracer uptake were evaluated. Final diagnosis was determined by histology (n = 9), clinical follow-up (n = 10), or by [18F]FET PET (n = 10).

Results

D-cis-[18F]FPro showed high uptake in both recurrent brain tumors (n = 11) and lesions classified as treatment-related changes (TRC) only (n = 16) (LBRmean 2.2 ± 0.7 and 2.1 ± 0.6, n.s.; LBRmax 3.4 ± 1.2 and 3.2 ± 1.3, n.s.). The untreated glioblastoma and the lesion showing reactive astrogliosis exhibited low D-cis-[18F]FPro uptake. Distribution of [18F]FET and D-cis-[18F]FPro uptake was discordant in 21/29 cases indicating that the uptake mechanisms are different.

Conclusion

The high accumulation of D-cis-[18F]FPro in pretreated brain tumors and TRC supports the hypothesis that tracer uptake is related to cell death. Further studies before and after therapy are needed to assess the potential of D-cis-[18F]FPro for treatment monitoring.

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Authors and Affiliations

  1. Institute of Neuroscience and Medicine (INM-3, -4, -5), Forschungszentrum Jülich, 52425, Jülich, Germany

    Antoine Verger, Gabriele Stoffels, Norbert Galldiks, Philipp Lohmann, Antje Willuweit, Bernd Neumaier, Stefanie Geisler & Karl-Josef Langen

  2. Department of Nuclear Medicine and Nancyclotep Imaging Platform, CHRU Nancy, Lorraine University, Nancy, France

    Antoine Verger

  3. IADI, INSERM, UMR 947, Lorraine University, Nancy, France

    Antoine Verger

  4. Department of Neurology, University Hospital Cologne, Cologne, Germany

    Norbert Galldiks

  5. Centre of Integrated Oncology (CIO), Universities of Cologne and Bonn, Cologne, Germany

    Norbert Galldiks

  6. Department of Nuclear Medicine, RWTH Aachen University Hospital, Aachen, Germany

    Karl-Josef Langen

  7. Section JARA-Brain, Jülich-Aachen Research Alliance (JARA), Jülich, Germany

    Karl-Josef Langen

Authors
  1. Antoine Verger
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  2. Gabriele Stoffels
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  3. Norbert Galldiks
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  4. Philipp Lohmann
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  5. Antje Willuweit
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  6. Bernd Neumaier
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  7. Stefanie Geisler
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  8. Karl-Josef Langen
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Corresponding author

Correspondence to Karl-Josef Langen.

Ethics declarations

The study was approved by both the local ethics committee and federal authorities, and all patients gave written informed consent before each PET investigation and the use of the data for scientific evaluations.

Conflict of Interest

The authors declare that they have no conflict of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed Consent

Informed written consent was obtained from all individual participants included in the study.

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Verger, A., Stoffels, G., Galldiks, N. et al. Investigation of cis-4-[18F]Fluoro-D-Proline Uptake in Human Brain Tumors After Multimodal Treatment. Mol Imaging Biol 20, 1035–1043 (2018). https://doi.org/10.1007/s11307-018-1197-8

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  • DOI: https://doi.org/10.1007/s11307-018-1197-8

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