Imaging of insulitis and beta cell mass in type 1 diabetes mellitus

PhD ceremony: Ms. V. di Gialleonardo, 11.00 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Imaging of insulitis and beta cell mass in type 1 diabetes mellitus

Promotor(s): prof. A. Signore, prof. R.A.J.O. Dierckx

Faculty: Medical Sciences

Insulitis (inflammation in the pancreas) and destruction of the insulin-producing beta cells in the islets of Langerhans, are important hallmarks of type 1 diabetes mellitus. This thesis describes the development of new tools using Positron Emission Tomography (PET) for the detection of functionality of beta cells, and infiltration of activated immune cells in the pancreas. To measure insulitis, the PET tracer[¹⁸F]FB-interleukin-2 was developed and validated in rodents. [¹⁸F]FB-Interleukin-2 is a small protein, which binds to the interleukin-2 receptor (CD25) on activated immune cells. PET imaging studies with [¹⁸F]FB-interleukin-2 in rodents gave excellent results in terms of sensitivity and pharmacokinetics. In diabetes-prone rats, the infiltration of activated immune cells into the pancreas could be easily detected and the imaging signal correlated well with the severity of the insulitis. For imaging of beta cell mass, the radio labeled serotonin precursor [¹¹C]HTP was investigated as a potential PET tracer. We demonstrated that uptake and the metabolism of [¹¹C]HTP in beta cells proceed via the serotonin pathway. In contrast, the serotonin pathway is not active in the exocrine pancreas. This difference was exploited to improve the contrast between islets of Langerhans and the surrounding exocrine tissue. Both non-invasive methods to visualize insulitis and pancreatic beta-cells mass may have important applications in diabetes research, leading to better understanding of the disease. In the clinic, these imaging probes may allow early diagnosis and monitoring of disease progression and treatment efficacy.