Imaging the Beta-Cell Mass: Why and How

Diabetes is a disorder characterized by beta-cell loss or exhaustion
and insulin deficiency. At present, knowledge is
lacking on the underlying causes and for the therapeutic recovery
of the beta-cell mass. A better understanding of diabetes
pathogenesis could be obtained through exact monitoring
of the fate of beta-cells under disease and therapy
conditions. This could pave the way for a new era of intervention
by islet replacement and regeneration regimens.
Monitoring the beta-cell mass requires a reliable method for
noninvasive in vivo imaging. Such a method is not available at
present due to the lack of a beta-cell-specific contrast agent.
The only existing method to monitor islet cells in vivo consists
of labeling islet transplants with iron nanoparticles prior
to transplantation and visualization of the transplanted islets
by magnetic resonance imaging (MRI). Therefore, accurate
assessment of the native beta-cell mass is still limited to autopsy
studies. Endeavors to find a biological structure specific
for beta-cells led to the discovery of potential candidates
that have been tested for noninvasive imaging. Among
them are the ligand to the vesicular monoamine transporter
type 2 (VMAT-2), which is called dihydrotetrabenazine
(DTBZ), antibodies to zinc transporter (ZnT-8) and the
monoclonal antibody IC2. While DTBZ and antibodies to
ZnT-8 showed binding activities to more than beta-cells, the
anti-IC2 monoclonal antibody showed binding properties
exclusively to insulin-producing beta-cells. This effect was
demonstrated in many previous investigations, and has been
further substantiated more recently. Thus, at present, IC2
seems to be the only useful marker for noninvasive functional
imaging of native beta-cells. Experiments with a radioisotope-
chelated IC2 structure on pancreas ex vivo
showed that the tracer specifically bound to the beta-cell
surface and could be detected by nuclear imaging. In the
near future, these promising findings may offer a new way
to monitor the beta-cell mass in vivo under disease and therapy
conditions so that we can learn more about diabetes
pathogenesis and options for disease prevention.
Keywords: diabetes · beta-cell · noninvasive imaging ·
IC2 · islet transplantation · MRI · PET · photoacoustic