Protein aggregation and folding as target for molecular imaging and radionuclide therapy

Amyloid-like aggregation of proteins is induced by short amyloidogenic Aggregation Prone Regions (APRs) within a protein sequence. These APRs can be used to develop synthetic amyloidogenic peptides called Pept-ins that target APRs via specific β-sheet aggregation interactions. Recently we identified radiolabelled Pept-ins for PET imaging of cancer and infection, targeting VEGFR2 and E. coli respectively. We want to investigate the broad potential of Pept-ins as a platform for molecular imaging and radionuclide therapy. Cells employ a complex cellular machinery consisting of ”chaperones” such as heat shock proteins (HSPs), for folding of proteins to their active conformation. Using microPET studies with a radiolabelled high-affinity HSP-90 inhibitor we recently found that tumour expression of HSP-90 is upregulated in various mouse tumour models. We want to further investigate the role of HSP90 in development and spreading of tumours as well as in neurodegenerative diseases using small molecule and peptide (including Pept-Ins) based vectors. In addition we will investigate the potential of HSP90 targeted radionuclide therapy for cancer.

Keywords:radionuclide therapy, Peptide Interferor (Pept-in), HSP90, positron emission tomography

Disciplines:Protein diagnostics, Proteins, Medical imaging and therapy not elsewhere classified, Radiopharmacy