Gd<sup>3+</sup>cFLFLFK conjugate for MRI: a targeted contrast agent for FPR1 in inflammation

Stasiuk, Graeme J.; Smith, Helen K.; Wylezinska-Arridge, Marzena; Tremoleda, Jordi L.; Trigg, William; Luthra, Sajinder K.; Iveson, Veronique Morisson; Gavins, Felicity N. E.; Long, Nicholas J.

doi:10.1039/c2cc37460a

Cited by 38 publications

(30 citation statements)

References 21 publications

(15 reference statements)

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“…In the past decade, FPR1 has demonstrated high specificity and affinity to a synthetic hexapeptide, cinnamoyl‐F‐(D)L‐F‐(D)L‐F (cFLFLF), which was utilized to deliver various payloads to different septic and sterile inflammatory loci for imaging purposes by us and others . For example, we have reported the application of a near infrared fluorescent (NIRF) probe, cFLFLF‐poly(ethylene glycol) ‐cyanine 7 (cFLFLF‐PEG‐Cy7) and a positron emission tomography (PET) probe, cFLFLF‐PEG‐ 64 Cu for non‐invasive imaging of inflammation with different animal models.…”

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confidence: 99%

Targeting formyl peptide receptor 1 of activated macrophages to monitor inflammation of experimental osteoarthritis in rat

Yang

Chordia

et al. 2016

Journal Orthopaedic Research

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Macrophages play a crucial role in the pathogenesis of osteoarthritis (OA). In this study, the feasibility of a formyl peptide receptor 1 (Fpr1)-targeting peptide probe cFLFLF-PEG- 64Cu via positron emission tomography (PET) imaging was investigated for detection of macrophage activity during development of OA. Monoiodoacetate (MIA) was intraarticularly injected into the knee joint of Sprague-Dawley rats to induce OA. Five days later, cFLFLF-PEG-64 Cu ($7,400 kBq/rat) was injected into the tail vein and microPET/CT imaging was performed to assess the OA inflammation by detecting infiltration of macrophages by Fpr1 expression. In addition, a murine macrophage cell line RAW264.7 and two fluorescent probes cFLFLF-PEG-cyanine 7 (cFLFLF-PEG-Cy7) and cFLFLF-PEG-cyanine 5 (cFLFLF-PEG-Cy5) were used to define the binding specificity of the peptide to macrophages. It was found with the MIA model that the maximal standard uptake values (SUV max ) for right (MIA treated) and left (control) knees were 17.96 AE 5.45 and 3.00 AE 1.40, respectively. Histological evaluation of cryomicrotome sections showed that Fpr1 expression, cFLFLF-PEG-Cy5 binding, and tartrate-resistant acid phosphatase activity were elevated in the injured synovial membranes. The in vitro experiments demonstrated that both fluorescent peptide probes could bind specifically to RAW264.7 cells, which was blocked by cFLFLF but not by the scramble peptide. The findings highlighted the use of cFLFLF-PEG- 64Cu/PET as an effective method potentially applied for detection and treatment evaluation of OA. ß

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Targeting formyl peptide receptor 1 of activated macrophages to monitor inflammation of experimental osteoarthritis in rat

Yang

Chordia

et al. 2016

Journal Orthopaedic Research

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“…[26] However, the 13 C chemical shift has not been thoroughly investigated because of the low sensitivity of the 13 C signal, which leads to the line broadening effect of the paramagnetic element. For thermometric application, we report the synthesis of 13 C-labeled TmDOTA ( were chemically synthesized from a commercially available compound (details are presented in the Supporting Information [27][28][29] ). [1][2][3][4][5][6][7][8][9][10][11][12][13] C]bromoacetate and [1][2][3][4][5][6][7][8][9][10][11][12][13] C] stearic acid were purchased from Cambridge Isotope Laboratory Inc. 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) was obtained from Avanti Polar Lipid.…”

Section: ] 119mentioning

confidence: 99%

¹³C‐TmDOTA as versatile thermometer compound for solid‐state NMR of hydrated lipid bilayer membranes

Umegawa

Tanaka

Matsumori

et al. 2015

Magnetic Reson in Chemistry

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Recent advances in solid-state nuclear magnetic resonance (NMR) techniques, such as magic angle spinning and high-power decoupling, have dramatically increased the sensitivity and resolution of NMR. However, these NMR techniques generate extra heat, causing a temperature difference between the sample in the rotor and the variable temperature gas. This extra heating is a particularly crucial problem for hydrated lipid membrane samples. Thus, to develop an NMR thermometer that is suitable for hydrated lipid samples, thulium-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate (TmDOTA) was synthesized and labeled with (13) C (i.e., (13) C-TmDOTA) to increase the NMR sensitivity. The complex was mixed with a hydrated lipid membrane, and the system was subjected to solid-state NMR and differential scanning calorimetric analyses. The physical properties of the lipid bilayer and the quality of the NMR spectra of the membrane were negligibly affected by the presence of (13) C-TmDOTA, and the (13) C chemical shift of the complex exhibited a large-temperature dependence. The results demonstrated that (13) C-TmDOTA could be successfully used as a thermometer to accurately monitor temperature changes induced by (1) H decoupling pulses and/or by magic angle spinning and the temperature distribution of the sample inside the rotor. Thus, (13) C-TmDOTA was shown to be a versatile thermometer for hydrated lipid assemblies. Copyright © 2015 John Wiley & Sons, Ltd.

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“…Using FPR-specific ligand cFLFLFK, neutrophil infiltration in the inflammatory foci could be visualized with various imaging modalities, including MRI 79, optical imaging 80, SPECT 81 and PET 82, 83. PET, using cFLFLFK-PEG- 64 Cu, could visualize inflammatory foci within the lung in an animal model of lung inflammation induced by Klebsiella pneumonia 82.…”

Section: Biomarkers For Inflammation Imagingmentioning

confidence: 99%

PET Imaging of Inflammation Biomarkers

Wu¹,

Li²,

Niu³

et al. 2013

Theranostics

161

114

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Inflammation plays a significant role in many disease processes. Development in molecular imaging in recent years provides new insight into the diagnosis and treatment evaluation of various inflammatory diseases and diseases involving inflammatory process. Positron emission tomography using 18F-FDG has been successfully applied in clinical oncology and neurology and in the inflammation realm. In addition to glucose metabolism, a variety of targets for inflammation imaging are being discovered and utilized, some of which are considered superior to FDG for imaging inflammation. This review summarizes the potential inflammation imaging targets and corresponding PET tracers, and the applications of PET in major inflammatory diseases and tumor associated inflammation. Also, the current attempt in differentiating inflammation from tumor using PET is also discussed.

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Gd³⁺cFLFLFK conjugate for MRI: a targeted contrast agent for FPR1 in inflammation

Cited by 38 publications

References 21 publications

Targeting formyl peptide receptor 1 of activated macrophages to monitor inflammation of experimental osteoarthritis in rat

Targeting formyl peptide receptor 1 of activated macrophages to monitor inflammation of experimental osteoarthritis in rat

¹³C‐TmDOTA as versatile thermometer compound for solid‐state NMR of hydrated lipid bilayer membranes

PET Imaging of Inflammation Biomarkers

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Gd3+cFLFLFK conjugate for MRI: a targeted contrast agent for FPR1 in inflammation

Cited by 38 publications

References 21 publications

Targeting formyl peptide receptor 1 of activated macrophages to monitor inflammation of experimental osteoarthritis in rat

Targeting formyl peptide receptor 1 of activated macrophages to monitor inflammation of experimental osteoarthritis in rat

13C‐TmDOTA as versatile thermometer compound for solid‐state NMR of hydrated lipid bilayer membranes

PET Imaging of Inflammation Biomarkers

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Product

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Gd³⁺cFLFLFK conjugate for MRI: a targeted contrast agent for FPR1 in inflammation

¹³C‐TmDOTA as versatile thermometer compound for solid‐state NMR of hydrated lipid bilayer membranes