Abstract
Specifying the exact localization of insulinoma remains challenging due to the lack of insulinoma-specific imaging methods. Recently, glucagon-like peptide-1 receptor (GLP-1R)-targeted imaging, especially positron emission tomography (PET), has emerged. Although various radiolabeled GLP-1R agonist exendin-4-based probes with chemical modifications for PET imaging have been investigated, an optimal candidate probe and its scanning protocol remain a necessity. Thus, we investigated the utility of a novel exendin-4-based probe conjugated with polyethylene glycol (PEG) for [18F]FB(ePEG12)12-exendin-4 PET imaging for insulinoma detection. We utilized [18F]FB(ePEG12)12-exendin-4 PET/CT to visualize mouse tumor models, which were generated using rat insulinoma cell xenografts. The probe demonstrated high uptake value on the tumor as 37.1 ± 0.4%ID/g, with rapid kidney clearance. Additionally, we used Pdx1-Cre;Trp53R172H;Rbf/f mice, which developed endogenous insulinoma and glucagonoma, since they enabled differential imaging evaluation of our probe in functional pancreatic neuroendocrine neoplasms. In this model, our [18F]FB(ePEG12)12-exendin-4 PET/CT yielded favorable sensitivity and specificity for insulinoma detection. Sensitivity: 30-min post-injection 66.7%, 60-min post-injection 83.3%, combined 100% and specificity: 30-min post-injection 100%, 60-min post-injection 100%, combined 100%, which was corroborated by the results of in vitro time-based analysis of internalized probe accumulation. Accordingly, [18F]FB(ePEG12)12-exendin-4 is a promising PET imaging probe for visualizing insulinoma.
Highlights
Insulinoma is a rare pancreatic neuroendocrine neoplasm (PanNEN) and causes hypoglycemia owing to insulin oversecretion[1]
This study investigated the utility of a novel PEGylated exendin-4-based probe for positron emission tomography (PET) imaging, [18F] FB(ePEG12)12-exendin-4, for insulinoma detection using Pdx1-Cre;Trp53R172H;Rbf/f mice and conventional model mice bearing insulinoma xenografts
In the male BALB/c slc-nu/nu mice bearing INS-1 xenografts in the right thigh (n = 5), INS-1 tumors were properly visible on the [18F]FB(ePEG12)12-exendin-4 PET/computed tomography (CT) images (Fig. 1A)
Summary
Insulinoma is a rare pancreatic neuroendocrine neoplasm (PanNEN) and causes hypoglycemia owing to insulin oversecretion[1]. Somatostatin receptor (SSTR)-targeted imaging approaches have demonstrated improved sensitivities, but are highlighted by limitations because insulinomas, especially benign ones, lack reasonable expression levels of SSTR subtype 2 and 5 8,9. They do not reflect endocrine functions of the tumors, thereby making it impossible to differentiate insulinoma from other panNENs in cases with multiple panNENs. Glucagon-like peptide-1 receptor (GLP-1R) is highly expressed on insulinomas[8,10]. This study investigated the utility of a novel PEGylated exendin-4-based probe for PET imaging, [18F] FB(ePEG12)12-exendin-4, for insulinoma detection using Pdx1-Cre;Trp53R172H;Rbf/f mice and conventional model mice bearing insulinoma xenografts
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