IDH-wildtype glioblastomas and grade III/IV IDH-mutant gliomas show elevated tracer uptake in fibroblast activation protein-specific PET/CT
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 pharmacokin...
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| Hauptverfasser: | , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
06 August 2019
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| In: |
European journal of nuclear medicine and molecular imaging
Year: 2019, Jahrgang: 46, Heft: 12, Pages: 2569-2580 |
| ISSN: | 1619-7089 |
| DOI: | 10.1007/s00259-019-04444-y |
| Online-Zugang: | Verlag, Volltext: https://doi.org/10.1007/s00259-019-04444-y
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| Verfasserangaben: | 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 |
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| 245 | 1 | 0 | |a IDH-wildtype glioblastomas and grade III/IV IDH-mutant gliomas show elevated tracer uptake in fibroblast activation protein-specific PET/CT |c 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 |
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| 520 | |a 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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| 650 | 4 | |a Glioblastoma | |
| 650 | 4 | |a Glioma | |
| 650 | 4 | |a MRI | |
| 650 | 4 | |a PET | |
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