[(131)I]N-(6-amino-2,2,4-trimethylhexyl)-2-[(5-iodo(3-pyridyl))carbonylamino]-3-(2-napthyl)propanamide.
An autoimmune process and other environmental factors that destroy pancreatic β cells in the pancreatic islet cells are known to promote the development of insulin-dependent diabetes mellitus (type 1 diabetes) in individuals genetically predisposed to the disease (1). As a consequence of the β cell destruction, the net mass of these cells in the islet cells is reduced and, due to reduced insulin production, maintenance of blood glucose to a proper physiological level is impaired. The most common type of diabetes, type 2, is primarily caused by insulin resistance as a result of low insulin secretion by the β cells. Type 2 diabetes can often be corrected with exercise, diet control, and, if necessary, medication (2). On diagnosis of diabetes, knowledge of the β cell mass (BCM) or volume is an important factor to devise a successful treatment for the condition (3). Changes in the BCM during the onset of diabetes is poorly understood, and only an indirect method that measures the amount of simulated insulin secretion by the pancreas is used to quantify the BCM in humans (4). However, the β cells appear to have a reserved capacity to produce insulin, thereby limiting the use of insulin secretion as a determinant of BCM (4). As an alternative to determine insulin secretion to quantify BCM, investigators evaluated a non-invasive positron emission tomography (PET) imaging technique to determine the BCM in rats with the use of <sup>11</sup>C- or <sup>18</sup>F-labeled dihydrotetrabenazine, which targets the vesicular monoamine transporter type 2 (VMAT2) in the pancreas (5-7). Although the VMAT2 has been used extensively for PET imaging of the brain in individuals suffering from Parkinson’s disease (8), its utilization for β cell imaging is still under investigation because the control of VMAT2 expression and function in these cells is not completely understood (4). The somatostatins (SST) and their receptors (SSTR) have not only been shown to be important for pancreatic development but are also implicated in diabetes mellitus and pancreatic cancer (9). Among the various SSTRs, SSTR1 and SSTR5 are considered to be biomarkers for the pancreatic β cells because they regulate insulin secretion and are found only in these cells (9, 10). Although several SST synthetic peptide analogs have been used to investigate the SSTRs (11), some non-peptide compounds have also been designed that show receptor specificity to the SSTRs, such as the SSTR1 (12). In an effort to develop an imaging compound for the measurement of BCM in the pancreas, a napthylalanine derivative, <sup>131</sup>I-labeled <i>N</i>-{6-[(tert-butoxy)carbonylamino]-2,2,4-trimethylhexyl}-2-{[5-(1,1-dimethyl-1-stannaethyl)(3-pyridyl)]carbonylamino}-3-(2-napthyl)propanamide) ([<sup>131</sup>I]IPC-β-AL3), with a binding specificity for the SSTR1, was synthesized, radioiodinated with <sup>131</sup>I, and studied for its biodistribution in normal and non-obese diabetic (NOD) mice by Amartey and colleagues (13, 14).