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European Journal of Nuclear Medicine and Molecular Imaging

Erschienen in:

11.02.2020 | Original Article

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

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

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 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 (SUV_max, SUV_mean) with and without normalization to healthy brain tissue and blood radioactivity obtained from 40 to 60 min summed dynamic images (PET_40–60) and ~ 60-min blood samples were calculated. Kinetic modelling using a two-tissue reversible compartmental model with a fractioned blood volume (V_B) was performed to determine the total distribution volume (V_T). 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. SUV_max and SUV_mean normalized to blood radioactivity from PET_40–60 and blood sampling, and V_T 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 V_B. Using Ki-67 index with a threshold > 4%, the majority of [¹⁸F]FLT metrics showed a high ability to identify aggressive meningiomas with SUV_mean 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.

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Titel: In vivo imaging of cell proliferation in meningioma using 3′-deoxy-3′-[18F]fluorothymidine PET/MRI
verfasst von: Asma Bashir
Tina Binderup
Mark Bitsch Vestergaard
Helle Broholm
Lisbeth Marner
Morten Ziebell
Kåre Fugleholm
Andreas Kjær
Ian Law
Publikationsdatum: 11.02.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 6/2020
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-020-04704-2

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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