Pancreatic neuroendocrine tumors (PNET) are rare, are classified as nonfunctional or functional, and have been discussed in detail by Batcher et al. (1). Nonfunctional PNETs usually grow in size and eventually cause a mass effect in the organ, whereas functional tumors secrete one (or more) active hormones and are subclassified on the basis of the hormone secreted by the cells constituting the tumor (e.g., insulinomas (secrete insulin), glucagonomas (secrete glucagon), somatostatinomas (secrete somatostatin), etc.). Insulinomas are the most common PNETs observed in the clinic, and biochemical tests of patients with these tumors show that the individuals have fasting hypoglycemia (below normal glucose levels) along with hyperinsulinemia (elevated levels of insulin) (1). Complete surgical resection of the tumor is considered to be the most suitable treatment and cure for the patient (2). Most insulinomas are small and benign, and they exist as single lesions. Imaging techniques such as computed tomography (CT), magnetic resonance imaging (MRI), and endoscopic ultrasound (EUS) are often used to detect and determine the location of these tumors on the pancreas (3). However, the preoperative detection of these lesions with noninvasive imaging is difficult because the techniques are either unable to distinguish the tumor from the normal parenchymal tissue in the pancreas (e.g., CT), are expensive (e.g., MRI), invasive, and successful detection of the tumor is operator-dependent (e.g., EUS) (3, 4). Investigators have shown that insulinomas characteristically express high levels of glucagon-like peptide 1 (GLP-1) receptors (GLP-1R), and radiolabeled GLP-1 analogs have been developed and evaluated for the detection of the PNETs (5). Although GLP-1 is the natural ligand for the GLP-1R, a major drawback of using this peptide to detect the lesions is that it is rapidly inactivated (half-life, ~2 min) by proteolytic enzymes while in circulation. As a consequence, investigators have used 111In- or 99mTc-labeled exendin-4 or its analogs (exendin is a peptide of 39 amino acids that has a 54% homology with GLP-1, acts as an agonist of the GLP-1R, and is not inactivated by proteolytic enzymes) with single-photon emission computed tomography to detect insulinomas in Rip1Tag2 mice that have spontaneous insulinoma (6, 7) and in humans (4). Investigators have also used positron emission tomography (PET) with structural analogs of exendin-4 conjugated to N-(2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethyl)-4-[18F]-fluorobenzamide ([18F]FBEM) for labeling with 18F (e.g., [18F]FBEM-[Cys0]-exendin-4 and [18F]FBEM-[Cys40]-exendin-4; for structural details of these compounds, see Kiesewetter et al. (5)) to detect xenograft tumors that overexpress GLP-1R in mice (5). In a continued effort to develop GLP-1 analogs that are not degraded by proteolytic enzymes, investigators synthesized EM3106B, an analog of GLP-1 that contains lactam bridges between residues 18–22 and 30–34 of the peptide, has an unnatural amino acid (2-aminoisobutyric acid at position 8 (to prevent proteolytic degradation of the peptide)), and has a cysteine residue on the C-terminus to allow labeling with [18F]-FBEM. The GLP-1 analog was labeled with 18F (by coupling it with [18F]-FBEM), and the final labeled compound ([18F]FBEM-EM3106B) was evaluated for the detection of subcutaneous insulinomas in nude mice (6).