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

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

doi:10.1039/c4dt02980a

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

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

^*Corresponding author for this work

Imaging Chemistry & Biology

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

Abstract

Non-invasive imaging of the inflammatory process can provide great insight into a wide variety of disease 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. This journal is

Original language	English
Pages (from-to)	4986-4993
Number of pages	8
Journal	Dalton Transactions
Volume	44
Issue number	11
DOIs	https://doi.org/10.1039/c4dt02980a
Publication status	Published - 2015

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title = "99mTc SPECT imaging agent based on cFLFLFK for the detection of FPR1 in inflammation",

abstract = "Non-invasive imaging of the inflammatory process can provide great insight into a wide variety of disease 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. This journal is",

author = "Stasiuk, {Graeme J.} and Holloway, {Paul M.} and Charlotte Rivas and William Trigg and Luthra, {Sajinder Kaur} and {Morisson Iveson}, Veronique and Gavins, {Felicity N.E.} and Long, {Nicholas J.}",

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AU - Stasiuk, Graeme J.

AU - Holloway, Paul M.

AU - Rivas, Charlotte

AU - Trigg, William

AU - Luthra, Sajinder Kaur

AU - Morisson Iveson, Veronique

AU - Gavins, Felicity N.E.

AU - Long, Nicholas J.

PY - 2015

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N2 - Non-invasive imaging of the inflammatory process can provide great insight into a wide variety of disease 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. This journal is

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

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