Dataset Information

Multi-tracer and multiparametric PET imaging to detect the IDH mutation in glioma: a preclinical translational in vitro, in vivo, and ex vivo study.

ABSTRACT:

Background

This translational study explores multi-tracer PET imaging for the non-invasive detection of the IDH1 mutation which is a positive prognostic factor in glioma.

Methods

U87 human high-grade glioma (HGG) isogenic cell lines with or without the IDH1 mutation (CRISP/Cas9 method) were stereotactically grafted into rat brains, and examined, in vitro, in vivo and ex vivo. PET imaging sessions, with radiotracers specific for glycolytic metabolism ([¹⁸F]FDG), amino acid metabolism ([¹⁸F]FDopa), and inflammation ([¹⁸F]DPA-714), were performed sequentially during 3-4 days. The in vitro radiotracer uptake was expressed as percent per million cells. For each radiotracer examined in vivo, static analyses included the maximal and mean tumor-to-background ratio (TBR_max and TBR_mean) and metabolic tumor volume (MTV). Dynamic analyses included the distribution volume ratio (DVR) and the relative residence time (RRT) extracted from a reference Logan model. Ex vivo analyses consisted of immunological analyses.

Results

In vitro, IDH1+ cells (i.e. cells expressing the IDH1 mutation) showed lower levels of [¹⁸F]DPA-714 uptake compared to IDH1- cells (p < 0.01). These results were confirmed in vivo with lower [¹⁸F]DPA-714 uptake in IDH+ tumors (3.90 versus 5.52 for TBR_max, p = 0.03). Different values of [¹⁸F]DPA-714 and [¹⁸F] FDopa RRT (respectively 11.07 versus 22.33 and 2.69 versus - 1.81 for IDH+ and IDH- tumors, p < 0.02) were also observed between the two types of tumors. RRT [¹⁸F]DPA-714 provided the best diagnostic performance to discriminate between the two cell lines (AUC of 100%, p < 0.01). Immuno-histological analyses revealed lower expression of Iba-1 and TSPO antibodies in IDH1+ tumors.

Conclusions

[18F]DPA-714 and [18F] FDopa both correlate with the presence of the IDH1 mutation in HGG. These radiotracers are therefore good candidates for translational studies investigating their clinical applications in patients.

SUBMITTER: Clement A

PROVIDER: S-EPMC8932106 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Multi-tracer and multiparametric PET imaging to detect the IDH mutation in glioma: a preclinical translational in vitro, in vivo, and ex vivo study.

Clément Alexandra A Zaragori Timothee T Filosa Romain R Ovdiichuk Olga O Beaumont Marine M Collet Charlotte C Roeder Emilie E Martin Baptiste B Maskali Fatiha F Barberi-Heyob Muriel M Pouget Celso C Doyen Matthieu M Verger Antoine A

Cancer imaging : the official publication of the International Cancer Imaging Society 20220318 1

<h4>Background</h4>This translational study explores multi-tracer PET imaging for the non-invasive detection of the IDH1 mutation which is a positive prognostic factor in glioma.<h4>Methods</h4>U87 human high-grade glioma (HGG) isogenic cell lines with or without the IDH1 mutation (CRISP/Cas9 method) were stereotactically grafted into rat brains, and examined, in vitro, in vivo and ex vivo. PET imaging sessions, with radiotracers specific for glycolytic metabolism ([<sup>18</sup>F]FDG), amino ac ...[more]

PMID: 35303961

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Dataset Information

Multi-tracer and multiparametric PET imaging to detect the IDH mutation in glioma: a preclinical translational in vitro, in vivo, and ex vivo study.

Background

Methods

Results

Conclusions

Publications

Multi-tracer and multiparametric PET imaging to detect the IDH mutation in glioma: a preclinical translational in vitro, in vivo, and ex vivo study.

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