Quantitative GLP-1 receptor imaging correlated to ex vivo distribution of In-111-exendin

In order to fully characterize the highly promising innovative tracer
In-111-DTPA-[K40]-Exendin 4 (In-111-exendin) in humans, we aim to correlate
quantitative SPECT imaging with ex vivo tracer distribution in patients
undergoing pancreatectomy for pancreatic cancer or chronic pancreatitis. We
propose to combine in vivo imaging with post-pancreatectomy
(micro)autoradiography, measurement of In-111-DTPA-[K40]-Exendin 4
concentrations in the pancreas using a gamma counter and morphometric
determination of the actual beta cell mass. By this means, we will establish
the relation between tracer uptake and beta cell mass in non-diabetic patients
and T2D patients. These highly relevant data will allow us to improve the
interpretation of clinical quantitative SPECT data in subsequent studies in
patients with T1D and T2D. In addition, high uptake has been observed in the
duodenum/pyloric area in patients in an ongoing study. At this point in time,
it remains unclear which cells are responsible for this uptake. It would be of
great interest to identify the GLP-1R positive cells in order to better
understand the physiological actions of GLP-1 agonists.

The primary objective is to correlate ex vivo 111In-exendin tracer accumulation
in the pancreas of patients undergoing pancreatectomy for pancreatic cancer or
chronic pancreatitis to establish the relation between tracer uptake and beta
cell mass in non-diabetic patients and patients with diabetes.
These highly relevant data will improve the interpretation of clinical
quantitative SPECT data in subsequent studies.

After recruitment of the participating individuals, all patients will undergo
an enrollment check at the Department of Nuclear Medicine consisting of a
medical interview and a physical examination performed by a qualified physician
(in case this is not done during intake and surgical evaluation for
pancreatectomy). Recent blood samples for standard laboratory checks (blood
counts, electrolytes, liver enzymes, inflammation parameters) that have been
taken prior to pancreatectomy, will be analyzed. Another visit is needed for an
oral glucose tolerance test and an glucose-dependent arginine-stimulation test.
One day prior to pancreatectomy, In-111-exendin will be administered to all
patients. We aim to include 50 patients into this study with a first interim
analysis that will be accomplished after participation of the first 15
patients.
After pancreatectomy, samples for histology and autoradiography will be taken
from the pancreatic head, body and tail and duodenum/pylorus if resected.
Tissue samples will be fixed in formalin and autoradiography will be performed
to correlate pancreatic uptake with the In-111-exendin tracer distribution ex
vivo. In case patients appear to have impaired glucose tolerance without being
diagnosed for diabetes earlier, patients will undergo a second oral glucose
tolerance test and (in case of improved glucose tolerance) an In-111-Exendin
scan after pancreatectomy.

The risk of serious side effects of the study medication is very low. Bruising
may occur after venous puncture. Measures like local pressure will be taken to
minimize the risk. The risk of sampling the pancreas is very low because the
biopsy is taken from resected pancreatic tissue
In conclusion, the risk of adverse events during this study is very low. On the
other hand, there is a very high (and increasing) incidence of diabetes
mellitus (especially type 2), which can lead to serious complications including
death. This study aims to establish an innovative imaging technology for the
non-invasive in vivo determination of the beta cell mass. Such a technology
would be an asset on our way to better understand the mechanisms involved in
the development of diabetes mellitus and can lead to the development of new
treatment options.
The subjects will not benefit directly from participating in this study.