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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 6/2020

01-06-2020 | Meningioma | Original Article

In vivo imaging of cell proliferation in meningioma using 3′-deoxy-3′-[18F]fluorothymidine PET/MRI

Authors: Asma Bashir, Tina Binderup, Mark Bitsch Vestergaard, Helle Broholm, Lisbeth Marner, Morten Ziebell, Kåre Fugleholm, Andreas Kjær, Ian Law

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 6/2020

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Abstract

Purpose

Positron emission tomography (PET) with 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) provides a noninvasive assessment of tumour proliferation in vivo and could be a valuable imaging modality for assessing malignancy in meningiomas. We investigated a range of static and dynamic [18F]FLT metrics by correlating the findings with cellular biomarkers of proliferation and angiogenesis.

Methods

Seventeen prospectively recruited adult patients with intracranial meningiomas underwent a 60-min dynamic [18F]FLT PET following surgery. Maximum and mean standardized uptake values (SUVmax, SUVmean) with and without normalization to healthy brain tissue and blood radioactivity obtained from 40 to 60 min summed dynamic images (PET40–60) and ~ 60-min blood samples were calculated. Kinetic modelling using a two-tissue reversible compartmental model with a fractioned blood volume (VB) was performed to determine the total distribution volume (VT). Expressions of proliferation and angiogenesis with key parameters including Ki-67 index, phosphohistone-H3 (phh3), MKI67, thymidine kinase 1 (TK1), proliferating cell nuclear antigen (PCNA), Kirsten RAt Sarcoma viral oncogene homolog (KRAS), TIMP metallopeptidase inhibitor 3 (TIMP3), and vascular endothelial growth factor A (VEGFA) were determined by immunohistochemistry and/or quantitative polymerase chain reaction.

Results

Immunohistochemistry revealed 13 World Health Organization (WHO) grade I and four WHO grade II meningiomas. SUVmax and SUVmean normalized to blood radioactivity from PET40–60 and blood sampling, and VT were able to significantly differentiate between WHO grades with the best results for maximum and mean tumour-to-whole-blood ratios (sensitivity 100%, specificity 94–95%, accuracy 99%; P = 0.003). Static [18F]FLT metrics were significantly correlated with proliferative biomarkers, especially Ki-67 index, phh3, and TK1, while no correlations were found with VEGFA or VB. Using Ki-67 index with a threshold > 4%, the majority of [18F]FLT metrics showed a high ability to identify aggressive meningiomas with SUVmean demonstrating the best performance (sensitivity 80%, specificity 81%, accuracy 80%; P = 0.024).

Conclusion

[18F]FLT PET could be a useful imaging modality for assessing cellular proliferation in meningiomas.
Appendix
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Metadata
Title
In vivo imaging of cell proliferation in meningioma using 3′-deoxy-3′-[18F]fluorothymidine PET/MRI
Authors
Asma Bashir
Tina Binderup
Mark Bitsch Vestergaard
Helle Broholm
Lisbeth Marner
Morten Ziebell
Kåre Fugleholm
Andreas Kjær
Ian Law
Publication date
01-06-2020
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 6/2020
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-020-04704-2

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