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.
