Effect of Gelofusine on GLP1-receptor Imaging
Condition: Diabetes Mellitus, Non-Insulin-Dependent; Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The highly promising and innovative tracer on 111In-DTPA-AHX-Lys40-Exendin 4 has been applied
      to determine beta cell mass in healthy volunteers and patients with type 1 diabetes. However,
      the high retention of the tracer in the kidneys was leading to a kidney/pancreas uptake ratio
      of 41±23. This high renal uptake is complicating absolute BCM quantification by SPECT
      imaging. In order to reduce the kidney/pancreas uptake ratio, investigators propose a
      co-infusion with the plasma expander Gelofusine since it has been shown in several
      pre-clinical and clinical studies that Gelofusine can reduce the renal retention of several
      other, closely related tracers. When investigators are able to reduce the kidney/pancreas
      uptake ratio, these findings will improve the interpretation of clinical quantitative SPECT,
      having important implications for therapeutic decision making for patients with diabetes,
      insulinomas or congenital hyperinsulinism, and may also have a major impact on our
      understanding of the pathophysiology of these diseases.
    

Detailed description: 
      Beta-cell imaging in vivo

      Reliable, sensitive and specific non-invasive methods for comprehensive structural and
      functional characterization of living pancreatic beta-cells in vivo (and in vitro) would not
      only enhance our understanding of the pathophysiology of various diseases, but also enable
      longitudinal in vivo assessment of beta cell mass (BCM) and distribution in patients with
      e.g. diabetes (including patients who received beta cell replacement therapy). Additionally,
      it can help in diagnosing insulinomas and congenital hyperinsulinism and when coupled to
      other biomarkers it could aid patient stratification and enable patient-specific optimized
      treatment strategies.

      Inhibiting the reabsorption of radiolabelled peptides

      It has been shown, both in vitro and in vivo, that the kidney uptake of radiolabelled
      peptides can be reduced by co-infusion of agents that inhibit the reabsorption of these
      peptides. One of these agents is succinylated gelatin (Gelofusine), a plasma expander that
      consists of a mixture of collagen-derived peptides. Previous clinical observations have shown
      that Gelofusine infusion results in tubular proteinuria of both albumin and β2-microglobulin.
      Although the exact mechanism for this proteinuria is not completely understood, the megalin
      receptor system is most likely involved. Based on pre-clinical studies in mice and rats, it
      has been known that kidney uptake is significantly reduced for various tracers when
      co-infused with Gelofusine, like 111In-Octreotide 111In-Minigastrin, 68Ga-exendin-4 and
      111In-DTPA-AHX-Lys40-Exendin 4. Additionally, it was shown that Gelofusine also reduces the
      renal retention of 111In- Octreotide by 45% in humans. In the current study, investigators
      will determine whether Gelofusine has also an effect on kidney retention of
      111In-DTPA-AHX-Lys40-Exendin 4 in humans.
    

Intervention name(s): Gelofusine; 111In-exendin 4 SPECT/CT; Placebo
Intervention type(s): Drug; Radiation; Drug
Intervention description(s): Infusion of gelofusine; 111In-exendin 4 SPECT/CT
Intervention MeSH terms: Exenatide; Polygeline
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: SPECT; radiopeptides; gelofusine; Beta cell