18F-PSMA PET/CT for visualization of glioblastoma multiforme

Currently, diagnosis of brain tumours is based on conventional gadolinium
enhanced T1-weighted magnetic resonance imaging (T1w-Gd MRI), which provides
images with high spatial resolution. It may however be difficult to
differentiate brain tumours from signal abnormalities caused by non-neoplastic
alterations in the tissue, especially after surgery, radiotherapy and
chemotherapy. Therefore, imaging biological and molecular characteristics by
positron emission tomography (PET) has gained attention.
2-[18F]-fluoro-2-deoxy-D-glucose (FDG) is widely used in oncology, but due to
high rate of glucose metabolism in normal brain, it is difficult and often
impossible to distinguish tumour tissue using this tracer. Glioblastoma
multiforme (GBM) is a highly vascularised tumour. Previous studies have shown
that prostate-specific membrane antigen (PSMA) is robustly expressed by the
tumour vascular endothelium of GBM and thus could be an interesting target for
diagnosis and treatment.

Primary objective:
* Determine the feasibility of using 18F-PSMA PET/CT for visualization of GBM.
Secondary objectives:
* Correlate PSMA RNA and protein expression with 18F-PSMA PET/CT uptake.

5 patients with detected/suspected GBM on T1w-Gd MRI will be included. On the
day before surgery, patients will undergo a MRI scan with gadolinium contrast
agent as standard pre-operative imaging for neuronavigation. Subsequently,
patients will be injected with 200 MBq 18F-PSMA, and undergo a PET/CT scan 120
minutes post-injection, as under these conditions high tracer uptake and high
tumor-to-background ratios have been observed in patients with prostate cancer.
After this scan patients will be hospitalized at the department of
neuro-surgery. The next day, tumour tissue will be resected and processed
following standard procedures for histological/immunohistochemical analysis by
the pathology department. From the resected material, additional pieces of
tissue will be frozen for PSMA protein and targeted RNA expression analysis
to determine correlations with tracer uptake.

The risk of serious side effects of the study medication is absent to minimal.
Bruising may occur after the venous puncture, measures like application of
local pressure will be taken to minimize the risk. Furthermore the expected
radiation dose is low (4,7 mSv), especially in comparison to the post-operative
radiotherapy these patients will receive.
Because of its high soft-tissue contract, MRI is still the first method of
choice for the assessment of brain tumors, however it has certain limitations.
These limitations include defining of tumor extension and grade, and
differentiation of tumor recurrence from necrosis or scarring. The use of
FDG-PET to distinguish recurrent tumor from radiation necrosis appeared
promising, however the high uptake in normal brain tissue imposes some
difficulties. 18F-FET has already been proven to outperform MRI and FDG-PET in
tumor delineation and identification of tumor recurrence in various clinical
trials, and because of its specificity for tumor vasculature, we expect the
same for 18F-PSMA-PET. This is why implementation of this technique in the
Radboudumc would be of benefit for glioma patients.