⁹⁹ᵐTc SPECT imaging agent based on cFLFLFK for the detection of FPR1 in inflammation

Stasiuk, Graeme J.; Holloway, Paul M.; Rivas, Charlotte; Trigg, William; Luthra, Sajinder Kaur; Morrison Iveson, Veronique; Gavins, Felicity N.E.; Long, Nicholas J.

Abstract

Non-invasive imaging of the inflammatory process can provide a great deal of insight into a wide variety of diseases states, aiding diagnosis, evaluation and effective targeted treatment. During inflammation, blood borne leukocytes are recruited, through a series of activation and adhesion steps, to the site of injury or infection where they migrate across the blood vessel wall into the tissue. Thus, tracking leukocyte recruitment and accumulation provides a dynamic and localised read out of inflammatory events. Current leukocyte imaging techniques require ex vivo labelling of patient blood, involving laborious processing and potential risks to both patient and laboratory staff. Utilising high affinity ligands for leukocyte specific receptors may allow for injectable tracers that label leukocytes in situ, omitting potentially hazardous ex vivo handling. Formyl peptide receptors (FPRs) are a group of G-protein coupled receptors involved in the chemotaxis and inflammatory functioning of leukocytes. Highly expressed on leukocytes, and up regulated during inflammation, these receptors provide a potential target for imaging inflammatory events. Herein we present the synthesis and initial in vitro testing of a potential Single Photon Emission Computed Tomography (SPECT) leukocyte tracer. The FPR1 antagonist cFLFLFK-NH₂, which displays high affinity with little physiological effect, has been linked via a PEG motif to a ⁹⁹ᵐTc chelate. This tracer shows in vitro binding to human embryonic kidney cells expressing the FPR1 receptor, and functional in vitro tests reveal cFLFLFK-NH₂ compounds to have no effect on inflammatory cell functioning. Overall, these data show that ⁹⁹ᵐTc.cFLFLFK-NH₂ may be a useful tool for non-invasive imaging of leukocyte accumulation in inflammatory disease states.

Citation

Stasiuk, G. J., Holloway, P. M., Rivas, C., Trigg, W., Luthra, S. K., Morrison Iveson, V., Gavins, F. N., & Long, N. J. (2015). ⁹⁹ᵐTc SPECT imaging agent based on cFLFLFK for the detection of FPR1 in inflammation. Dalton Transactions : an international journal of inorganic chemistry, 44(11), 4986-4993. https://doi.org/10.1039/c4dt02980a

• Journal Article Type: Article
• Acceptance Date: Jan 7, 2015
• Online Publication Date: Jan 7, 2015
• Publication Date: Jan 1, 2015
• Deposit Date: Feb 23, 2016
• Publicly Available Date: Feb 23, 2016
• Journal: Dalton transactions
• Print ISSN: 1477-9226
• Electronic ISSN: 1477-9234
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 44
• Issue: 11
• Pages: 4986-4993
• DOI: https://doi.org/10.1039/c4dt02980a
• Keywords: ⁹⁹ᵐTc SPECT imaging; Inflammation
• Public URL: https://hull-repository.worktribe.com/output/411133
• Publisher URL: http://pubs.rsc.org/en/Content/ArticleLanding/2015/DT/c4dt02980a#!divAbstract
• Additional Information: This is the authors accepted manuscript of an article published in Dalton transactions, 2015, v.44 issue 11.
• Contract Date: Feb 23, 2016