oa Editorial [Hot topic:Beta Cell Imaging - Why we need it and what has been Achieved (Executive Editor: Martin Gotthardt)]

When I was first confronted with the idea of in vivo imaging of beta cells, I was not sure whether this was meant seriously. For a nuclear medicine physician or a radiologist, imaging of tumors is part of the daily routine. Diabetes imaging seems far from the scope of clinically relevant imaging. If diabetes is diagnosed, it is usually done based on clinical findings such as pathological oral glucose tolerance. So, what would you need imaging for? Interestingly, since nearly two decades, a small group of people has been trying to find a way to measure the pancreatic beta cell mass or to follow the fate of transplanted islets in vivo. The National Institutes of Health have organized the first workshop on imaging of pancreatic beta cells in 1999, and 3 others have followed in 2003, 2006, and 2009 [1, 2]. In the past years, there have also been specific calls in the field of beta cell imaging from the National Institutes of Health, the Juvenile Diabetes Research Foundation, the European Union and several other grant-giving institutions. So, obviously there is a need for in vivo imaging of beta cells although it is not necessarily obvious to nondiabetologists. According to the WHO, there are currently 180 million people suffering from diabetes mellitus world wide (mostly type 2 diabetes (T2D)) with an expected doubling of this number until 2030 [3]. The WHO predicts that in upper- and middle-income countries the number of diabetes-related deaths will increase by 80% between 2006 and 2015. Despite these impressive numbers and although risk factors for the development of diabetes are well-known, the precise molecular mechanisms leading to the decrease in beta-cell mass responsible for the development of impaired glucose tolerance and diabetes still remain to be elucidated. Specifically, we do not know the natural history of betacell mass loss in human diabetes, nor do we have convincing evidence on beta-cell neogenesis and the preserved actual beta-cell mass in patients with impaired glucose tolerance - we are only able to determine the functional beta cell mass by glucose clamping, a rather invasive method. With the advent of innovative treatment regimens in T2D claiming to preserve or even increase the beta cell mass, it becomes clear that we are in need of reliable, sensitive, specific, and non-invasive methods for detection of living pancreatic beta-cells in vivo to validate these claims. Furthermore, such imaging technology might help to enhance our understanding of the pathophysiology of T2D as well as T1D. Apart from direct determination of beta-cell mass, such imaging techniques may also be useful for imaging of the response of beta-cells to conditions leading to beta-cell dysfunction and eventually apoptosis. In his article, Burkhard Goke from the University of Munich, Germany, summarizes the current challenges in diabetes research that could more efficiently be addressed with in vivo imaging methods [4]. Although the search for imaging technology to detect vital islets of Langerhans in vivo has begun early in the 1990ies, no imaging method is in clinical or research routine use to date. Paty et al. have summarized the results of the 2003 NIH workshop on beta cell imaging. Their final statement was that “Early efforts are underway to develop such means (i.e. technology for beta cell imaging) using a variety of techniques including MRI, PET, and optical imaging.”[5]. Obviously, clinical application of the available imaging methods for in vivo detection of beta cells were considered to still be premature. So, has there been progress in the field in the past years? Indeed, excellent imaging methods for in vivo imaging of insulinomas, beta-cell derived tumours, have currently become available. Kauhanen and colleagues give a concise overview over the current state-of-the-art in imaging of insulinomas and beta-cell hyperplasia and they focus on the impressive results that have been obtained with 18F-DOPA PET imaging [6]. However, imaging of tumours (or focal beta cell hyperplasia) is less challenging than imaging of physiological tissue that is not over-expressing the target that is binding the radiolabeled specific ligand.Even worse, in the case of the pancreatic beta cells, the target tissue is spread all over the organ in the tiny islets of Langerhans, contributing to not more than 1-2% of the total pancreatic mass-conditions that are far from optimal for in vivo imaging. In their overview, Brom et al. focus on the technical aspects and challenges of the development of radiotracers for beta cell imaging and give a concise summary of the most important steps that have been taken so far [7]. Although some approaches they describe may hold great promise to reach the ultimate goals of successful in vivo imaging of beta cells, most of the tracers they describe have failed in respect to reaching this aim....