9 January 2017
A collaboration between Pfizer and the Washington University School of Medicine offers a possibility for improved treatment of diabetes. Radiologist Suzanne Lapi and colleagues have succeeded in developing an imaging technique that allows them to “see” the mass of insulin-producing beta cells present in the pancreas. This development could lead to more tailored treatment plans for diabetes patients, based on the progression of the disease.
In diabetics, the body doesn’t use insulin effectively, leading to increased insulin production and a gradual decrease in the mass of pancreatic beta cells. Until recently, the only way to quantify beta cell mass was by autopsy.
Lapi and her team were able to visualize beta cell mass using a PET scan, an imaging technique that uses the body’s metabolism of radioactive compounds to map organs and tissues. They separately tagged exendin-4, a synthetic peptide that selectively binds to pancreatic beta cells, with the radioactive isotopes copper-64 and gallium-68, to visualize beta cell mass in rats.
“We have a long history of radio-labelling peptides, mostly in cancer,” says Lapi. “The idea of using molecular imaging to look at the biology of cancer and drug delivery is a much more mature field that we've looked at for a long time. With our collaborators we started discussing whether we could use this for other things—such as imaging beta cells.”
The team also assessed how well the isotopes bound to exendin-4 by means of two different metal chelators (molecules that bind metal ions). “The subtle variations in the structure of the peptide changes its metabolism, and also the affinity to the receptor. Tiny changes can have a big impact when you’re designing these agents, just like when you're designing a drug,” says Lapi.
By detecting the radioactivity of the bound radioisotopes with a PET scanner, researchers and clinicians can chart the state of an animal’s, or patient’s, insulin-producing capability. The study may prove beneficial for drug development by highlighting compounds that bind and enter the beta cells. “It's a two-pronged approach. We can use these tools to see what's going on in the body, but we can also label new compounds to assess their suitability for drug development.”
References
- Bandara, N., Zheleznyak, A., Cherukuri, K., Griffith, D. A., Limberakis, C. et al. Evaluation of Cu-64 and Ga-68 Radiolabeled Glucagon-Like Peptide-1 Receptor Agonists as PET Tracers for Pancreatic β cell Imaging. Molecular Imaging and Biology. (2015). | article
