Abstract
Multiple endocrine neoplasia type 1 (MEN1) is an endocrine tumor syndrome caused by heterozygous mutations in the MEN1 tumor suppressor gene. The MEN1 pancreas of the adolescent gene carrier frequently contain diffusely spread pre-neoplasias and microadenomas, progressing to macroscopic and potentially malignant pancreatic neuroendocrine tumors (P-NET), which represents the major death cause in MEN1. The unveiling of the molecular mechanism of P-NET which is not currently understood fully to allow the optimization of diagnostics and treatment. Glucagon-like peptide 1 (GLP-1) pathway is essential in islet regeneration, i.e. inhibition of β-cell apoptosis and enhancement of β-cell proliferation, yet involvement of GLP-1 in MEN1 related P-NET has not yet been demonstrated. The objective of this work was to investigate if normal sized islets of Men1 heterozygous mice have increased Glucagon-like peptide-1 receptor (GLP-1R) expression compared to wild type islets, and if this increase is detectable in vivo with positron emission tomography (PET) using [68Ga]Ga-DO3A-VS-Cys40-Exendin-4 (68Ga-Exendin-4). 68Ga-Exendin-4 showed potential for early lesion detection in MEN1 pancreas due to increased GLP1R expression.
Highlights
One of the most common inherited genetic syndromes related to neuroendocrine tumors is multiple endocrine neoplasia type 1 (MEN 1)
To clarify if GLP1 pathway is involved in initiation of proliferation in Multiple endocrine neoplasia type 1 (MEN1) pancreatic neoplasm and if GLP-1 receptor (GLP-1R) expression could reflect this transformation[19], we performed quantitative PCR as well as 68Ga-Exendin-4/positron emission tomography (PET)-studies in Men[1] mice
The clinical recognition of MEN1 related pancreatic neuroendocrine tumors (P-NET) are generally correlated to their abnormal hormone secretion
Summary
One of the most common inherited genetic syndromes related to neuroendocrine tumors is multiple endocrine neoplasia type 1 (MEN 1). Pancreatic neuroendocrine tumors (P-NET) occur in more than 80% of MEN1 patients[1] and is the major reason for MEN1-related death[2,3,4]. Treatment of these patients demands multidisciplinary care including surgery, chemotherapy and targeted therapies[5]. The proliferating endocrine cells[11] in Men[1] mice serve as a valuable model for studies of the pathophysiology and molecular events of importance for initiation of tumorigenesis in MEN1 P-NETs using preclinical in vitro, ex vivo and in vivo methods. To clarify if GLP1 pathway is involved in initiation of proliferation in MEN1 pancreatic neoplasm and if GLP-1R expression could reflect this transformation[19], we performed quantitative PCR as well as 68Ga-Exendin-4/PET-studies in Men[1] mice
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