Exendin PET/CT for imaging of paragangliomas

Because of the variability in genetic origin amongst paragangliomas (PGLs),
functional imaging is not unequivocal. Existing methods show good but variable
results, warranting the search for additional molecular imaging targets. We aim
to evaluate the glucagon-like peptide 1 receptor (GLP-1R) as a novel target for
molecular imaging of PGLs. For this we will use the tracer 68Ga-NODAGA-exendin
4 for positron emission tomography/ computed tomography (PET/CT) imaging.

The primary objective is to examine the feasibility of 68Ga-exendin-4 PET/CT
for localizing and characterizing PGL.

In this prospective pilot imaging study we will perform 68Ga-exendin-4 PET/CT
in 10 patients with confirmed PGL who have undergone CT and somatostatin
receptor (SSTR) PET/CT and are scheduled for surgery. We will administer 100 ±
5 MBq 68Ga-NODAGA-exendin-4 to 10 patients in total. In the first 3 patients we
will perform PET/CT imaging 1, 2 and 4 hours after injection to determine the
optimal imaging timepoint, which will be applied in the remaining patients.
The images will be reconstructed and evaluated by a nuclear medicine physician
who is blinded to the results of the CT and SSTR PET/CT to assess tumor
detection. Additionally, quantitative analysis of 68Ga-exendin-4 and SSTR PET
images will be performed. After the patients have undergone surgery,
immunohistochemical analysis of surgical specimens will be performed to assess
GLP-1R expression and correlate this with in vivo tracer uptake. Imaging and
immunohistochemistry (IHC) results will be correlated to the genetic origin of
the PGLs.

Potential adverse events that could occur based on the pharmacological effects
of 68Ga-NODAGA-exendin-4 and the observations in clinical trials with exenatide
so far namely include hypoglycaemia following injection and nausea with
vomiting. These effects are expected to be less pronounced than in previous
studies because the injected peptide amount will be more than 10 times lower.
Also, PGL patients are less prone to develop hypoglycaemia because of the
overproduction of catecholamines, which promotes hyperglycaemia. As
hypoglycaemia requires immediate stabilization of the glucose homeostasis,
blood glucose levels will be followed for 2 hours after injection. Upon
lowering of blood glucose levels, these will be stabilized using intravenous
glucose infusion if needed.
Next to this, potential adverse events could occur because of the
cardiovascular effects (hypotensiona and tachycardia) of 68Ga-NODAGA-exendin-4.
These effects are expected to be minimal because of the low peptide dose of the
tracer and the short-acting nature of exendin-4. To monitor these effects,
heart rate and blood pressure of all patients will be monitored until 2 hours
after injection.
The total expected radiation dose (68Ga en CT) expected from the PET/CT scan is
very low; about 5.1 mSv .