Beta Cell Imaging as Part of “Imaging on Metabolic Diseases”

Abstract

Currently, radionuclide imaging after injection of radiolabeled tracers seems to be the most promising approach to noninvasively determine the beta cell mass (BCM) in vivo. Despite the limited resolution of positron emission tomography (PET) and single photon emission computed tomography (SPECT), the very high sensitivity of these imaging modalities allows detection of very low radiotracer concentrations. Since the noninvasive imaging modalities that offer the highest spatial resolution, i.e., computed tomography (CT) and magnetic resonance imaging (MRI), which are not able to resolve single islets in vivo, radionuclide imaging would be the method of choice for beta cell imaging. However, noninvasive visualization of the pancreatic beta cells is a highly challenging endeavor. The beta cells are located in the islets of Langerhans in the pancreas. The islets are small (usually between 50 and 400 $μ$m), only account for 1--2 {%} of the total pancreatic mass, and are spread throughout the pancreas (Bonner-Weir 1994; Weir et al. 1990). Targeting of these small structures spread through an organ is highly challenging when compared to tumor imaging, where a focal solid mass containing the target cells is visualized. Moreover, the islets consist of several cell types (beta cells, alpha cells, delta cells, and pp cells) with the beta cells representing around 60--80 {%} of the islet mass, making specific visualization of beta cells even more difficult. Since PET and SPECT cannot resolve single islets, let alone beta cells, a highly beta cell-specific radiotracer is required. Only when the radiotracer specifically accumulates in beta cells and not in other cell types of the endocrine or exocrine pancreas, the accumulation of the radiotracer in the pancreas could be used as a surrogate measure of the beta cell mass. To enable this, a target specifically expressed on beta cells and an optimal respective ligand should be selected for the development of beta cell targeting radiotracers. In contrast to tumor imaging, where several targets are overexpressed, beta cells express endogenous levels of receptors leading to generally lower accumulation of radiotracers when compared to tumor cells. In this book chapter, the challenges regarding tracer development and preclinical and clinical characterization will be discussed in detail.