Feasibility of amylin imaging in pancreatic islets with β-amyloid imaging probes

Abstract

Islet amyloid deposition composed of amylin aggregates is regarded as one of the hallmarks of type 2 diabetes mellitus (T2DM). For the diagnosis of T2DM, several nuclear medical imaging probes have been developed. However, there have been no reports regarding the development of imaging probes targeting amylin. In this report, we investigated the feasibility of amylin imaging using [(125)I]IPBF as one of the model compounds of β-amyloid (Aβ) imaging probes. In in vitro experiments, [(125)I]IPBF exhibited high binding affinity for amylin aggregates (Kd = 8.31 nM). Moreover, autoradiographic images showed that [(125)I]IPBF specifically bound to islet amyloid composed of amylin. These results suggest the potential application of Aβ imaging probes to amylin imaging. In addition, [(125)I]IPBF is one of the promising lead compounds for amylin imaging, and further structural optimization based on [(125)I]IPBF may lead to useful tracers for the in vivo imaging of islet amyloids in the pancreas.

Figure 1. Chemical structure of [¹²⁵I]IPBF.

Figure 2. Saturation curve of [¹²⁵I]IPBF for amylin aggregates.

Figure 3. Chemical structure of previously reported Aβ imaging probes.

Figure 4. Chemical structure of pyridylbenzofuran derivatives.

Figure 5. Comparison of autoradiographic images of [¹²⁵I]IPBF with pancreatic tissue sections from a T2DM patient and two healthy controls (A, and D and G, respectively).

The same sections were also stained with thioflavin-S (B, and E and H, respectively). Immunohistochemical staining with antibodies against amylin (C, and F and I, respectively), Aβ_1-42 (J), and Aβ_1-40 (K). Pancreatic tissue sections from a T2DM patient (A, B, C, J, and K) and two different healthy donors (D, E, and F: 71-year-old man; G, H, and I: 28-year-old man).