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European Journal of Nuclear Medicine and Molecular Imaging

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01-11-2019 | Glioblastoma | Original Article

IDH-wildtype glioblastomas and grade III/IV IDH-mutant gliomas show elevated tracer uptake in fibroblast activation protein–specific PET/CT

Authors: Manuel Röhrich, Anastasia Loktev, Annika K. Wefers, Annette Altmann, Daniel Paech, Sebastian Adeberg, Paul Windisch, Thomas Hielscher, Paul Flechsig, Ralf Floca, Dominik Leitz, Julius P. Schuster, Peter E. Huber, Jürgen Debus, Andreas von Deimling, Thomas Lindner, Uwe Haberkorn

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 12/2019

Abstract

Purpose

Targeting fibroblast activation protein (FAP) is a new diagnostic approach allowing the visualization of tumor stroma. Here, we applied FAP-specific PET imaging to gliomas. We analyzed the target affinity and specificity of two FAP ligands (FAPI-02 and FAPI-04) in vitro, and the pharmacokinetics and biodistribution in mice in vivo. Clinically, we used ⁶⁸Ga-labeled FAPI-02/04 for PET imaging in 18 glioma patients (five IDH-mutant gliomas, 13 IDH-wildtype glioblastomas).

Methods

For binding studies with ¹⁷⁷Lu-radiolabeled FAPI-02/04, we used the glioblastoma cell line U87MG, FAP-transfected fibrosarcoma cells, and CD26-transfected human embryonic kidney cells. For pharmacokinetic and biodistribution studies, U87MG-xenografted mice were injected with ⁶⁸Ga-labeled compounds followed by small-animal PET imaging and ¹⁷⁷Lu-labeled FAPI-02/04, respectively. Clinical PET/CT scans were performed 30 min post intravenous administration of ⁶⁸Ga-FAPI-02/04. PET and MRI scans were co-registrated. Immunohistochemistry was done on 14 gliomas using a FAP-specific antibody.

Results

FAPI-02 and FAPI-04 showed high binding specificity to FAP. FAPI-04 demonstrated higher tumor accumulation and delayed elimination compared with FAPI-02 in preclinical studies. IDH-wildtype glioblastomas and grade III/IV, but not grade II, IDH-mutant gliomas showed elevated tracer uptake. In glioblastomas, we observed spots with increased uptake in projection on contrast-enhancing areas. Immunohistochemistry showed FAP-positive cells with mainly elongated cell bodies and perivascular FAP-positive cells in glioblastomas and an anaplastic IDH-mutant astrocytoma.

Conclusions

Using FAP-specific PET imaging, increased tracer uptake in IDH-wildtype glioblastomas and high-grade IDH-mutant astrocytomas, but not in diffuse astrocytomas, may allow non-invasive distinction between low-grade IDH-mutant and high-grade gliomas. Therefore, FAP-specific imaging in gliomas may be useful for follow-up studies although further clinical evaluation is required.

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Title: IDH-wildtype glioblastomas and grade III/IV IDH-mutant gliomas show elevated tracer uptake in fibroblast activation protein–specific PET/CT
Authors: Manuel Röhrich
Anastasia Loktev
Annika K. Wefers
Annette Altmann
Daniel Paech
Sebastian Adeberg
Paul Windisch
Thomas Hielscher
Paul Flechsig
Ralf Floca
Dominik Leitz
Julius P. Schuster
Peter E. Huber
Jürgen Debus
Andreas von Deimling
Thomas Lindner
Uwe Haberkorn
Publication date: 01-11-2019
Publisher: Springer Berlin Heidelberg
Keywords: Glioblastoma
Astrocytoma
Glioma
Magnetic Resonance Imaging
Magnetic Resonance Imaging
Glioma
Astrocytoma
Glioblastoma
Positron Emission Tomography
Astrocytoma
Glioblastoma
Glioma
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 12/2019
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-019-04444-y

At a glance: The STEP trials

Springer Medicine

IDH-wildtype glioblastomas and grade III/IV IDH-mutant gliomas show elevated tracer uptake in fibroblast activation protein–specific PET/CT

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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