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.
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.
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).
[18F]FLT PET could be a useful imaging modality for assessing cellular proliferation in meningiomas.
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- CT :
European Association of Neuro-Oncology
Epidermal growth factor receptor
Image-derived input function
Genes of interest
Kirsten RAt Sarcoma viral oncogene homologue
Matrix metallopeptidases 2 and 9
Magnetic resonance imaging
Proliferating cell nuclear antigen
Positron emission tomography
Quantitative polymerase chain reaction
Receiver operating characteristic
Region of interest
Somatostatin receptor subtype 2
Standardized uptake value
TIMP metallopeptidase inhibitors 3 and 4
Thymidine kinase 1
Tumour-to-parent fraction ratio
Tumour-to-white matter ratio
- V B :
Blood volume fraction
Vascular endothelial growth factor A
Volume of interest
World Health Organization
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The authors would like to thank the technical staff Nadia Azizi, Marianne Federspiel, Jakup Martin Poulsen, and Karin Stahr and chemists at Clinic of Clinical Physiology, Nuclear Medicine & PET, for help with PET scanning and patient care. The authors would also like to thank the nuclear medicine specialist, Oriol Puig, for helping with kinetic modelling images for the study. Finally, a special thanks to the statistician, Lasse Anderberg, for helping with ROC analyses.
The work was supported by a grant from the Danish Cancer Society (R146-A9508–16-S2). The Siemens mMR hybrid PET/MR system at Copenhagen University Hospital Rigshospitalet was donated by the John and Birthe Meyer Foundation.
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the Scientific Health Ethics Committee of the Capital region, Copenhagen, Denmark (reference number: H-15006091) and was based on the Declaration of Helsinki II (2013) and the principles of “good clinical practices”.
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This article is part of the Topical Collection on Oncology—Brain.
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Bashir, A., Binderup, T., Vestergaard, M.B. et al. In vivo imaging of cell proliferation in meningioma using 3′-deoxy-3′-[18F]fluorothymidine PET/MRI. Eur J Nucl Med Mol Imaging (2020). https://doi.org/10.1007/s00259-020-04704-2
- Thymidine kinase 1
- Ki-67 index