Congenital Hyperinsulinism Clinical Trial
Official title:
The Physiology of Glucagon-like-peptide-1 Espression in Patients With Endogenous Hyperinsulinism: Correlation With Histopathology
The primary objective is the in vivo and ex vivo investigation of the expression and distribution of the GLP-1R in the pancreas of CHI patients.
Congenital hyperinsulinism (CHI) is a rare disease of infants characterized by the presence
of functionally defective non-neoplastic beta-cells with inappropriate (over-) secretion of
insulin, leading to life-threatening hypoglycaemia. Beta cells specifically express the
glucagon-like-peptide-1 (GLP-1R), which could be a promising target for diagnostic and
therapeutic purposes. In this study we propose to investigate the physiology of GLP-1
receptor expression in CHI. Expression of the GLP-1 receptor will be quantified in vivo by
68Ga-NODAGA-exendin-4 PET/CT. This data will be compared with post-surgical autoradiography
and morphometric determinations.
Furthermore, we will evaluate 68Ga-exendin-4 PET/CT for the pre-operative localization of
foci of over-secreting beta cells in CHI and the discrimination between focal and diffuse
CHI. We will compare GLP-1R PET/CT to the currently used pre-operative imaging technique
(18F-DOPA PET combined with contrast enhanced CT). To compare these imaging techniques
according to sensitivity, we will analyze intra-operative findings and clinical outcomes.
These highly relevant data will allow us to evaluate the expression of GLP-1R in CHI and its
usefulness as a target for diagnosis of this disease. Since the localization of foci in CHI
and the discrimination between focal and diffuse CHI is challenging, surgical removal of
unnecessary large portions of the pancreas in frequently necessary. Evaluation of a better
target for pre-operative imaging would therefore be of great value.
Objective:
The primary objective is the in vivo and ex vivo investigation of the expression and
distribution of the GLP-1R in the pancreas of CHI patients. A 68Ga-NODAGA-exendin 4 PET/CT
will be performed in all patients included in this study. The results of quantitative imaging
will then be compared to GLP-1R expression and autoradiography of surgical specimens to
determine the interdependency of radiotracer uptake, beta cell mass and GLP-1R expression.
Furthermore, GLP-1R imaging will be compared to the standard imaging techniques now used in
pre-operative imaging of children with CHI. All patients will undergo the standard imaging
procedure, consisting of an 18F-DOPA PET scan combined with a contrast-enhanced CT. The
results of the GLP-1R imaging will be compared to standard imaging in respect to sensitivity
for localization of the lesion and discrimination between focal and diffuse CHI. This will be
determined by the comparison of the results of pre-operative imaging with intra-operative
findings.
Also, the safety (side-effects) of 68Ga-NODAGA-exendin and 18F-DOPA will be assessed.
Furthermore, dosimetric calculations will be performed and the minimum radioactivity dose of
68Ga-NODAGA-exendin 4 to obtain acceptable/reliable images will be determined.
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