Effect of Gelofusine on 111In-DTPA-AHX-Lys40-Exendin 4 uptake in the kidney

We hypothesize that Gelofusine will reduce the kidney uptake of 111In-labeled
exendin in humans by enhancing the excretion of 111In-labeled exendin.This has
already been shown in rodents for this tracer and for other tracers
(e.g.111In-Octreotide) in humans.

Primary Objective:

The primary objective is to determine whether the administration of Gelofusine
will reduce the kidney uptake of 111In-labeled exendin in humans by enhancing
the excretion of 111In-labeled exendin.

These highly relevant data can potentially improve the interpretation of
clinical quantitative SPECT and can have important implications for imaging of
pancreatic beta cell mass in diabetes patients as well as therapeutic decision
making for patients with insulinomas or congenital hyperinsulinism.



Secondary Objective(s):
Determine whether the administration of Gelofusine affects pancreatic uptake of
111In-labeled exendin based on quantitative analysis of SPECT images.

Cross-over study to prove that the administration of Gelofusine reduces the
kidney uptake of 111In-labeled exendin in healthy, adult volunteers.

All individuals will undergo physical examination and blood sampling for
standard laboratory parameters (first visit). Prior to SPECT acquisition,
participants will be injected with111In-DTPA-[K40]-Exendin 4. Patients will
undergo two acquisitions: one time in combination with saline (control) and the
second time in combination with Gelofusine.Injection of the radiopharmaceutical
may theoretically result in nausea and headache as has been reported for (much
higher doses of) Byetta® in therapeutic studies. In addition, single cases of
low blood pressure and low blood glucose levels have been described after
accidental heavy overdosing of Byetta®. However, in another study (CPOP-EX), we
did not observe any side or adverse effects after 111In-DTPA-[K40]-Exendin 4
injection in 20 patients. The expected radiation exposure will not exceed 10
mSv and is therefore considered minimal to little. Bruising may occur after
venous puncture. In conclusion, the risk of adverse events during this study is
very low and, therefore, the additional risk for volunteers participating to
this study is considered to be moderate.
Gelofusine is a registered medicinal product. Although not frequently reported,
side effects are allergy reactions like skin reactions and anaphylaxis, fever
and chills. Therefore, participants will be closely monitored.
If we are able to reduce the kidney/pancreas uptake ratio, these data will have
an important impact on the interpretation of clinical quantitative SPECT, which
in turn will have important implications for our understanding of the course of
diabetes as well as therapeutic decision making for patients with insulinomas
or congenital hyperinsulinism.