Applications in Diagnostics

Lowering costs and the burden

The attachment of a chemical moiety that emits a quantifiable signal (a fluorescent, enzymatic or luminiscent moiety) to our peptides can lead to an alternative diagnostic method to antibody and antibody fragments with the added benefit of the relative low cost of production and modification of small peptides. This cost reduction may help to spread this diagnostic tool to the markets of the developing world, where fungal infections have the largest mortality rates and were health care is largely affected by economic constraints. Moreover, if the peptides prove to have a high species-specificity, the diagnosis based on them may give more information for a proper therapy choice, potentially reducing the toxicity risks associated with the use of broad spectrum antimycotics.

In vivo diagnosis and the potential of artificial selection

Short peptides are currently being used as diagnostic tools for certain kind of cancers. These peptides are naturally produced by humans and have their natural binding proteins in the surface of cells; however, they have been optimized to increase their half-life and their affinity towards their natural target, and they also have been modified with radionuclides that make it possible to detect the location of tumors -cells were their binding proteins are overrepresented- with PET or SECT imaging.

The most common isotopically labelled peptide used for diagnosisis a ¹¹¹In-labelled somatostatin analogue, known as OctreoScan^TM, which is used to diagnose a variety of tumors. Other peptides under develompent are cholecystokinin/gastrin analogues, glucagon-like peptide-1, bombesin, chemokine receptor CXCR4 targeting peptides, RGD peptides, exendin, Substance P, LHRH, neurotensin, α-M2, α-M2H and VIP.

Following the same rationale, our artificially selected peptides can be modified and optimized to increase their binding affinity and their half-life. The peptides can then be tagged with radionuclides to enable the diagnosis by imaging techniques. The results of such a diagnostic method will give more information about the localization and spread of the fungal infection inside the patient's body than any of the currently available diagnostic methods.

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References

• 1. Fani, M., et al., (2012), Radiolabeled peptides: valuable tools for the detection and treatment of cancer, Theranostics, 2(5).


• 2. Laverman, P., (2012), Radiolabelled peptides for oncological diagnosis, Eur J Nucl Med Mol Imaging, 39 (Suppl I).