123Iodine-labelled anti-VCAM-1 antibody scintigraphy in the assessment of experimental colitis

Sans, Miquel; Fuster, David; Vazquez, A Lopez; Setoain, Francisco Javier; Piera, Carlos; Piqué, Josep M.; Panés, Julián

doi:10.1097/00042737-200101000-00006

Cited by 18 publications

(17 citation statements)

References 29 publications

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“…The strict temporal and spatial regulation of VCAM-1 in the development and progression of atherosclerosis [5][6][7][8][9] makes it a prime candidate for development of the next generation of targeted diagnostics and therapeutics. Several approaches have been described previously using radiolabeled Abs to detect VCAM-1 expression; 12,13 however, this approach has resulted in very modest target-tobackground ratios, limiting its use for in vivo cardiovascular imaging. To overcome these limitations, we commenced development of an agent that not only decorated the endothelial surface but was internalized by endothelial cells ("biological amplification through intracellular trapping").…”

Section: Discussionmentioning

confidence: 99%

“…9 Comparable to mouse atherosclerosis, VCAM-1 expression is induced early in human atheroma and is an important element in the inflammatory component of atherosclerosis, contributing to monocyte and lymphocyte recruitment from adventitial vessels and the arterial lumen. 3,10,11 Although several approaches have been described to image VCAM-1 expression using radiolabeled antibodies (Abs), 12,13 these agents usually result in modest target-to-background ratios, limiting their use for in vivo cardiovascular imaging.…”

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confidence: 99%

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Detection of Vascular Adhesion Molecule-1 Expression Using a Novel Multimodal Nanoparticle

Kelly

Allport

Tsourkas

et al. 2005

Circulation Research

413

360

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Abstract-Endothelial vascular adhesion molecule-1 (VCAM-1) is a critical component of the leukocyte-endothelial adhesion cascade, and its strict temporal and spatial regulation make it an ideal target for imaging and therapy. The goal of this study was to develop novel VCAM-1-targeted imaging agents detectable by MRI and fluorescence imaging using phage display-derived peptide sequences and multimodal nanoparticles (NPs). We hypothesized that VCAM-1-mediated cell internalization of phage display-selected peptides could be harnessed as an amplification strategy to chaperone and trap imaging agents inside VCAM-1-expressing cells, thus improving target-to-background ratios. To accomplish our goal, iterative phage display was performed on murine endothelium under physiological flow conditions to identify a family of VCAM-1-mediated cell-internalizing peptides. One specific sequence, containing the VHSPNKK motif that has homology to the ␣-chain of very late antigen (a known ligand for VCAM-1), was shown to bind VCAM-1 and block leukocyte-endothelial interactions. Compared with VCAM-1 monoclonal antibody, the peptide showed 12-fold higher target-to-background ratios. A VHSPNKK-modified magnetofluorescent NP (VNP) showed high affinity for endothelial cells expressing VCAM-1 but surprisingly low affinity for macrophages. In contrast, a control NP without VCAM-1-targeting sequences showed no affinity for endothelial cells. In vivo, VNP successfully identified VCAM-1-expressing endothelial cells in a murine tumor necrosis factor-␣-induced inflammatory model and colocalized with VCAM-1-expressing cells in atherosclerotic lesions present in cholesterol-fed apolipoprotein E apoE Ϫ/Ϫ mice. These results indicate that: (1) small peptide sequences can significantly alter targeting of NPs, (2) the used amplification strategy of internalization results in high target-to-background ratios, and (3)

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Detection of Vascular Adhesion Molecule-1 Expression Using a Novel Multimodal Nanoparticle

Kelly

Allport

Tsourkas

et al. 2005

Circulation Research

413

360

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“…A possible strategy is represented by the complexation of our imaging probe with radioisotopes, followed by their implementation in nuclear medicine, which has a superior sensitivity when compared to MRI. Regarding the former imaging approach, Sans et al 18 and Broisat et al 46 have reported VCAM-1 detection with 123 I-labeled monoclonal antibody in experimental colitis 18 and with 123 I-and 99m Tc-labeled molecular fragment of the major histocompatibility complex-1 in Watanabe heritable hyperlipidaemic rabbits. 46 The drawback represented by the low anatomical resolution mainly in the case of atherosclerotic pathology could be surmounted by a multimodal imaging approach such as PET/CT and PET/MRI imaging systems.…”

Section: Discussionmentioning

confidence: 99%

“…The imaging of VCAM-1 expression has thus been approached with antibodies or peptides conjugated to nuclear, 18 magnetooptical, 19,20 or ultrasound probes. 21 However, the size of most atherosclerotic lesions is below the spatial resolution of nuclear or ultrasound imaging systems.…”

Section: Introductionmentioning

confidence: 99%

Magnetic Resonance Molecular Imaging of Vascular Cell Adhesion Molecule-1 Expression in Inflammatory Lesions Using a Peptide-Vectorized Paramagnetic Imaging Probe

et al. 2009

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The vascular cell adhesion molecule-1 (VCAM-1) has distinct roles in inflammatory cell recruitment to the damaged vessel wall. In the present work, a cyclic heptapeptide phage displayed library was screened in vitro during four rounds of biopanning. On the basis of Kd and IC50 values, a peptide (encoded as R832) was selected for in vitro and in vivo validation. After conjugation to Gd-DOTA, VCAM-1 imaging was assessed by MRI on a model of T cell mediated hepatitis, induced in mice by concanavalin A. On histological samples, the location of biotinylated R832 (R832-Bt) around liver veins in hepatitis resembles the pattern of MRI enhancement. Gd-DOTA-R832 was then assessed on ApoE(-/-) mice and produced an important signal enhancement of the aortic wall, while R832-Bt interacted with morphologic structures comparable to those marked by anti-VCAM-1 antibody. In conclusion, the in vitro and in vivo evaluation of peptide R832 suggests a specific interaction with the targeted biomolecule. Its conjugation to imaging reporters could assist the diagnosis of inflammatory diseases.

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“…This "cellular trapping" strategy aimed at amplifying tracer signal and optimizing signal-to-noise was adopted primarily to improve upon prior in vivo imaging studies that had demonstrated limited utility of radiolabeled anti-VCAM-1 antibodies as molecular imaging probes [19,20]. After successive rounds of selection, the cyclic peptide CVHSPNKKC (termed VHS), homologous to the α-chain of VLA-4, a ligand of VCAM-1 expressed on circulating hematopoietic cells, was identified.…”

Section: Multimodal Nanoparticlesmentioning

confidence: 99%

Molecular Imaging of Vascular Inflammation with Nanoparticles

Thukkani

Glaus

Welch

2010

curr cardiovasc imaging rep

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Innovation in molecular imaging is poised to fundamentally advance the field of diagnostic medical imaging related to atherosclerosis. By detecting molecular signatures and cellular processes in vivo, advanced molecular imaging techniques offer a highly sensitive means to diagnose disease perhaps at preclinical stages. In conjunction with advances in imaging capability, materials science, and synthetic chemistry, nanoparticles have emerged as molecular imaging platforms possessing several salient advantages over traditional molecular imaging probes. Nanoparticle-based imaging platforms may be loaded with therapeutic agents, thereby not only improving detection of pathophysiologic changes in vivo but also limiting off-target toxicity associated with conventional medical therapies through targeted drug delivery. Accordingly, this review details the various advantages associated with nanoparticles in general, as well as highlights recent studies with a diverse collection of multimodal and nuclear nanoparticle imaging agents designed to detect atherosclerotic vascular inflammation in vivo.

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123Iodine-labelled anti-VCAM-1 antibody scintigraphy in the assessment of experimental colitis

Abstract: 123I-labelled anti-VCAM-1 MAb scintigraphy allows an accurate evaluation of colonic inflammatory damage in trinitrobenzenesulphonic acid-induced colitis, suggesting a potential role for this imaging technique in the assessment of human IBD.

Cited by 18 publications

References 29 publications

Detection of Vascular Adhesion Molecule-1 Expression Using a Novel Multimodal Nanoparticle

Detection of Vascular Adhesion Molecule-1 Expression Using a Novel Multimodal Nanoparticle

Magnetic Resonance Molecular Imaging of Vascular Cell Adhesion Molecule-1 Expression in Inflammatory Lesions Using a Peptide-Vectorized Paramagnetic Imaging Probe

Molecular Imaging of Vascular Inflammation with Nanoparticles

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