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18F-Fluorocholine PET uptake correlates with pathologic evidence of recurrent tumor after stereotactic radiosurgery for brain metastases

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Radiographic changes of brain metastases after stereotactic radiosurgery (SRS) can signify tumor recurrence and/or radiation necrosis (RN); however, standard imaging modalities cannot easily distinguish between these two entities. We investigated whether 18F-Fluorocholine uptake in surgical samples of the resected lesions correlates with pathologic evidence of recurrent tumor and PET imaging.

Methods

About 14 patients previously treated with SRS that developed radiographic changes were included. All patients underwent a preoperative 40-min dynamic PET/CT concurrent with 392 ± 11 MBq bolus injection of 18F-Fluorocholine. 18F-Fluorocholine pharmacokinetics were evaluated by standardized uptake value (SUV), graphical analysis (Patlak plot; KiP) and an irreversible two-compartment model (K1, k2, k3, and Ki). 12 out of 14 patients were administered an additional 72 ± 14 MBq injection of 18F-Fluorocholine 95 ± 26 minutes prior to surgical resection. About 113 resected samples from 12 patients were blindly reviewed by a neuropathologist to assess the viable tumor and necrotic content, microvascular proliferation, reactive gliosis, and mono- and polymorphonuclear inflammatory infiltrates. Correlation between these metrics 18F-Fluorocholine SUV was investigated with a linear mixed model. Comparison of survival distributions of two groups of patients (population median split of PET SUVmax) was performed with the log-rank test.

Results

Exactly 10 out of 12 patients for which surgical samples were acquired exhibited pathologic recurrence. Strong correlation was observed between SUVmax as measured from a surgically removed sample with highest uptake and by PET (Pearson’s r = 0.66). Patients with 18F-Fluorocholine PET SUVmax > 6 experienced poor survival. Surgical samples with viable tumor had higher 18F-fluorocholine uptake (SUV) than those without tumor (4.5 ± 3.7 and 2.6 ± 3.0; p = 0.01). 18F-fluorocholine count data from surgical samples is driven not only by the percentage viable tumor but also by the degree of inflammation and reactive gliosis (p ≤ 0.02; multivariate regression).

Conclusions

18F-Fluorocholine accumulation is increased in viable tumor; however, inflammation and gliosis may also lead to elevated uptake. Higher 18F-Fluorocholine PET uptake portends worse prognosis. Kinetic analysis of dynamic 18F-Fluorocholine PET imaging supports the adequacy of the simpler static SUV metric.

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Author information

Authors and Affiliations

  1. Department of Medical Physics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Milan Grkovski, Bradley J. Beattie, Pat B. Zanzonico & John L. Humm

  2. Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Zachary A. Kohutek & Kathryn Beal

  3. Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN, USA

    Zachary A. Kohutek, Robert J. Young & Ronald G. Blasberg

  4. Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Heiko Schöder

  5. Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Heiko Schöder

  6. Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Cameron W. Brennan, Viviane S. Tabar & Philip H. Gutin

  7. Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Cameron W. Brennan & Jason T. Huse

  8. Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Zhigang Zhang

  9. Pathology Department, MD Anderson Cancer Center, Houston, TX, USA

    Jason T. Huse

  10. Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Jason T. Huse & Marc K. Rosenblum

  11. Department of Neurology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Ronald G. Blasberg

  12. Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA

    Ronald G. Blasberg

Authors
  1. Milan Grkovski
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  2. Zachary A. Kohutek
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  3. Heiko Schöder
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  4. Cameron W. Brennan
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  5. Viviane S. Tabar
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  6. Philip H. Gutin
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  7. Zhigang Zhang
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  8. Robert J. Young
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  9. Bradley J. Beattie
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  10. Pat B. Zanzonico
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  13. Ronald G. Blasberg
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  14. John L. Humm
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  15. Kathryn Beal
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Corresponding author

Correspondence to Kathryn Beal.

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Funding information

This study was funded by the NIH grant 1R21 CA170289-01A1 (Principal Investigator, Kathryn Beal; corresponding, John L. Humm and Ronald G. Blasberg), R01 CA194321 (Principal Investigator: John L. Humm) and the MSK Radiochemistry & Molecular Imaging Probes Core, supported in part through the NIH/NCI Cancer Center Support Grant P30 CA008748 (Principal Investigator: Craig B. Thompson).

Conflict of interest

RJY declares consulting and grant support from Agios and consulting for Puma, Icon, and NordicNeuroLab. Other authors declare no potential conflicts 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 (Memorial Sloan Kettering Cancer Center’s Institutional Review Board, Protocol #13-199; registered under ClinicalTrials.gov Identifier NCT02037945) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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

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This article is part of the Topical Collection on Oncology – Brain

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Grkovski, M., Kohutek, Z.A., Schöder, H. et al. 18F-Fluorocholine PET uptake correlates with pathologic evidence of recurrent tumor after stereotactic radiosurgery for brain metastases. Eur J Nucl Med Mol Imaging 47, 1446–1457 (2020). https://doi.org/10.1007/s00259-019-04628-6

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  • DOI: https://doi.org/10.1007/s00259-019-04628-6

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