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DOI: 10.1055/s-0039-1683524
Fibroblast Activation Protein specific PET: A novel imaging method for IDH-wildtype Glioblastomas and IDH-mutant Gliomas
Publication History
Publication Date:
27 March 2019 (online)
Ziel/Aim:
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. Clinically, we used 68Ga-labelled FAPI-02/04 for PET-imaging in 18 glioma patients (5 IDH-mutant gliomas, 13 IDH-wildtype glioblastomas).
Methodik/Methods:
For binding studies with 177Lu- and 68Ga-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- and 177Lu- labeled compounds and analyzed by small-animal PET. Clinical PET/CT Scans were performed 30 minutes post i.v. administration of 68Ga-FAPI-02/04. PET- and MRI-scans were co-registrated. FAP immunohistochemistry was done in 14 gliomas.
Ergebnisse/Results:
FAPI-02 and FAPI-04 showed high binding specificity to FAP. FAPI-04 showed higher tumor accumulation and delayed elimination than FAPI-02. 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 fibroblast-like and perivascular FAP-positive cells in glioblastomas and anaplastic IDH-mutant astrocytomas.
Schlussfolgerungen/Conclusions:
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 and be useful for follow-up studies. The heterogeneous tracer uptake in glioblastomas may be helpful for biopsy planning. FAP-specific imaging in gliomas needs further evaluation.