Targeting integrin αvβ6 with gallium-68 tris (hydroxypyridinone) based PET probes

Abstract

Expression of the cellular transmembrane receptor αvβ6 integrin is mostly restricted to malignant epithelial cells in a wide variety of carcinomas, including pancreatic and others derived from epithelial tissues. Thus, this protein is considered an attractive target for tumour imaging and therapy. Two different ⁶⁸Ga hexadentate tris (3,4-hydroxypyridinone) (THP) chelators were produced in this study and coupled to the αvβ6 integrin-selective peptide <i>cyclo</i>(FRGDLAFp(NMe)K) <i>via</i> NHS chemistry. Radiolabelling experiments confirmed a high radiochemical yield of the two PET probes. In addition, cellular binding studies showed high binding affinities in the nanomolar range. The two integrin αvβ6-peptide-THP synthesized and radiolabeled in this study will facilitate <i>in vivo</i> monitoring of transmembrane receptor αvβ6 integrin by using the advantage of THP chemistry for rapid, efficient and stable gallium chelation.