[68Ga]Ga-PSMA-11 PET/MR-imaging of malignant intra-axial brain tumors; primary assessment of PSMA expression, optimization of compound delivery and determination of theranostic potential.

PSMA is a transmembrane protein specifically expressed in the vascular
endothelium of malignant brain tumors, most notably glioblastoma (GBM) and not
in healthy brain parenchyma. It has been shown to be involved in
(neo)angiogenesis and endothelial cell invasion. Since the development of
68Ga-labeled PSMA ligands, investigators are not only equipped to
non-invasively visualize PSMA expression on GBM (neo)vasculature in vivo by
means of PET, but also to use it as a therapeutic target. Therapeutic targeting
of malignant brain tumor (neo)vasculature is attractive as it may be exposed to
a therapeutic agent much more readily than the tumor parenchyma itself, which
is protected by the blood-brain barrier. The primary aim of this study is to
confirm PSMA as suitable diagnostic and theranostic target in patients with
intra-axial brain tumors by means of [68Ga]Ga-PSMA-HBEC-CC ([68Ga]Ga-PSMA-11)
PET. The secondary aim is to assess whether uptake is increased with
intra-arterial injection in those tumors that show uptake after intravenous
injection of [68Ga]Ga-PSMA-11.

The primary objective is to evaluate the uptake, including the distribution, of
[68Ga]Ga-PSMA-11 in enhancing glioma and brain metastases eligible for
(re-)resection by performing [68Ga]Ga-PSMA-11 PET/MRI scans, in order to study
the potential of PSMA as a diagnostic and therapeutic target. In case of a
positive [68Ga]Ga-PSMA-11 PET signal at the tumor site, the secondary objective
is to perform semi-quantitative (i.e., SUVmean and SUVmax) comparison of tracer
uptake in the primary tumor upon intravenous versus local intra-arterial
injection of [68Ga]Ga-PSMA-11, in order to determine the optimal route of
administration. Tertiary objectives are (i) to calculate SUV
tumor-to-background ratio*s in order to determine PSMA specificity, (ii) to
evaluate [68Ga]Ga-PSMA-11 biodistribution in order to determine sites
potentially at risk for toxicity, (iii) to assess the number of lesions
visualized by [68Ga]Ga-PMSA-11 PET and by MRI in order to establish whether new
metastatic lesions may be found, (iv) to perform semi-quantitative lesion by
lesion comparison of tracer uptake (in case of metastases), (v) to correlate
the SUV of the tumor to the degree of immunohistochemical PSMA expression, (vi)
to perform diagnostic interpretation of lesions (i.e., differentiation between
recurrent/residual tumor and radiation necrosis).

Non-randomized, single center, prospective imaging study.

Risks associated with venous and arterial puncture (i.e., infection,
rebleeding). Risks associated with catheterization of the intracranial vessels
(i.e., thromboembolic events and vessel spasm, shown to be <1%). Risks
associated with [68Ga]Ga-PSMA-11 injection (i.e., allergic reactions,
radiation). Burden associated with the procedures mentioned above (i.e., fear
of and pain from puncture). Burden associated with undergoing a PET/MRI (i.e.,
laying still for a certain time, noise, possible claustrophobia). Time burden
(i.e., one or two hospital day visits). This study offers no benefit for
patients. The study will not involve minors or incapacitated subjects.