Imaging and treatment of CHI: The BetaCure Project

BetaCure is a large research project to develop novel technologies for imaging and treatment of diseases in which too much insulin is produced, namely CHI (congenital hyperinsulinism) and AHH (adult hyperinsulinemic hypoglycaemia). The BetaCure project is sponsored by the European Union. 17 different industrial partners and university hospitals from 8 European countries participate. All these partners combine their expertise to search for a solution for these two rare diseases.

The project is in fact centered around one molecule: exendin. This molecule was first discovered in the saliva of a gilamonster, a lizard living in the South West of the United States and northern Mexico. When exendin from the gilamonster is injected into a human, it will specifically bind to beta cells in the pancreas. This is a very interesting property of exendin, because it’s the beta cells that cause insulin overproduction  in CHI.

The beta cells in CHI do not function as they should. They produce inappropriate amounts of insulin and this can result in life-threatening low blood glucose levels. To treat this disease, a surgeon will often remove part of the pancreas containing the diseased beta cells, or even the whole pancreas. A great disadvantage of this treatment is the risk of developing diabetes mellitus and digestion problems. If surgery is not possible, the patient will stay on lifelong medication and is thus not cured.

In the BetaCure project, the exendin molecule is used for imaging and treatment of CHI. For these purposes, the exendin is provided with a tag. This can be a radioactive or a fluorescent tag. In this way the exendin gives a signal that can be detected with special equipment.

If a radioactive tag is used, a PET (Positron Emission Tomography) scan of the whole body can be made, showing the exact location of the beta cells. Such a scan indicates whether the CHI has a focal or a diffuse form and can help a medical doctor to take decisions on the treatment with surgery or medicines. BetaCure aims to show that a scan with exendin is more specific than the currently used scan to visualize CHI (18F-DOPA).

If a fluorescent tag is used, a surgeon can see exactly which cells are the beta cells during the surgery, enabling him to specifically remove the parts of the pancreas containing the diseased cells without having to remove the whole pancreas. This way the risk of developing diabetes is expected to be much lower. This technique is called ‘image guided surgery’. In addition, a new microscope will be developed that the surgeon can use in the operating theater to check the tissue that was just removed during surgery.

Moreover, exendin can be labeled with a quite extraordinary tag, a so called photodynamic tag. If this tag is irradiated with laser light, it will form radicals that kill the beta cells. Then surgery is not necessary anymore, because the beta cells are destroyed by this ‘photo dynamic therapy’. This technique and the necessary irradiation equipment will be developed during the BetaCure project and tested in patients with AHH and CHI.

The combination of these new imaging and therapy techniques is expected to greatly improve diagnostics and treatment for people suffering from CHI.


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