Single Photon Emission Computed Tomography Imaging Agents for Formyl Peptide Receptors 1 and 2

Abstract

Formyl Peptide Receptors (FPR) 1 and 2 are key in the signalling pathway of inflammation, and are found on leucocytes in particular neutrophils. Inflammation is a major marker of many disease states in particular Ischaemia-reperfusion injury and atherosclerosis.1 Identifying cells with high expression of FPR1 and FPR2 is important in the diagnosis and therapy of these diseases. Single Photon Emission Computed Tomography (SPECT) is an incredibly sensitive imaging modality and ideal for imaging receptors on the surface of cells as they are only present in extremely low concentrations. Two peptides have been identified as targets for FPR1 and FPR2, cFLFLFK2 and WKYMVm3 respectively. cFLFLFK is a hexapeptide with cinnamoyl group at the c-terminus, which acts as an antagonist for FPR1. WKYMVm has been shown to have agonistic effect on FPR2. These two peptides have been modified with 99mTc chelates to give SPECT imaging agents for FPR1 and FPR2. The biological properties of the agents have been investigated so that they maintain specific binding to the FPR. The results obtain demonstrate that the FPRs (in particular FPR1 and FPR2) provide potential targets for visualising inflammation in disease. The research has been supported by the BBSRC and GE Healthcare.