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This review discusses nuclear imaging of inflammation using molecular probes beyond fluoro-d-glucose, is structured by cellular targets, and focuses on those tracers that have been successfully applied clinically.

Somatostatin receptor (SSTR)-based imaging and therapy has emerged as well-established modality in neuroendocrine tumors. However, its role in inflammation imaging is still evolving. We present a 48-year-old male with metastatic neuroendocrine tumor who underwent lutetium-177-based somatostatin receptor-based therapy. The post-therapy scan showed a focal tracer uptake in the left calf muscle in addition to the expected tracer uptake at the primary and metastatic sites. Further, cross-sectional imaging and biochemical investigations revealed peripheral vascular disease (PVD). The incidental tracer uptake in the calf on post-therapy scan potentiates the role of somatostatin receptor scintigraphy in identifying macrophage-specific inflammatory reactions.

The role of nuclear imaging in the characterization of high-risk atherosclerotic plaque is increasing thanks to its high sensitivity to detect radiopharmaceuticals signal in tissues. Currently, 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is the most studied and widely used radiopharmaceutical for the molecular imaging of atherosclerotic plaques with positron emission tomography (PET). [18F]FDG PET is a valuable tool to non-invasively detect, monitor and quantify inflammatory processes occurring in atherosclerotic plaques. The aim of this review is to gather insights provided by [18F]FDG PET to better understand the role of inflammation in the definitions of the vulnerable plaque and the vulnerable patient. Alternatives radiopharmaceuticals targeting inflammation and other potential high-risk plaque related processed are also discussed.

The process of inflammation (with or without infection) forms part of essentially every major debilitating disease. Early detection and accurate distinction of inflammation from infection are important to optimize and individualize therapy. Nuclear medicine is ideally suited for the detection of pathologic changes early on and is able to target a magnitude of role players involved in the aforementioned processes. Hybrid modalities such as PET/CT and PET/MRI offer high spatial resolution that combines morphologic and pathophysiological changes and add various quantification possibilities that are preferable in these settings. It follows then that the development of PET radiopharmaceuticals is imperative to make use of these latest advances. Gallium-68 (Ga-68)-based tracers are exceptionally well suited to these indications, considering the year-round availability from a single generator, the relative cost-effectiveness, and relative ease of labeling. Over the past few years, the development of Ga-68-based tracers has understandably exploded with a recent growing interest in infection and inflammation imaging. This review aims to highlight some of the most important and interesting advances made with Ga-68-based PET/CT in the field of infection and inflammation imaging.

International audience; Background: Inflammation is a share process in atherosclerosis and stroke and is thought to be a key player in the evolution of these diseases. Ten years ago, inflammation imaging with magnetic resonance imaging (MRI) was considered very promising for both pre-clinical and clinical studies of atherosclerosis and stroke. Contribution: We report here contributions to the field of inflammation imaging with USPIO-enhanced MRI. The goal was to investigate the life cycle of USPIOs in the body, and how the MRI signal has been impacted during their bio-interactions and bioprocessing. Those mechanisms were applied to pre-clinical longitudinal studies of inflammation in atherosclerosis and at the acute stage of ischemic stroke thus allowing the monitoring of treatment effects. Conclusion: This review presents the contribution of the collaborative research project under the "TecSan" grant from the French Research Agency (ANR) as well as pre-clinical and clinical perspectives of USPIO's inflammation MRI in atherosclerosis and stroke. (C) 2018 Published by Elsevier Masson SAS on behalf of AGBM.

We aim to investigate the clinical onset, computed tomography (CT) and magnetic resonance (MR) imaging findings, and follow-up of patients with cerebral amyloid angiopathy (CAA)-related inflammation, an uncommon but clinically striking presentation of CAA. We retrospectively reviewed the clinical manifestations, CT/MR imaging findings, and outcome of ten consecutive patients with CAA-related inflammation. In each patient, a brain CT study was performed at hospital admission, and brain MR imaging was carried out 2 to 4 days later. Clinical and radiologic follow-up findings were evaluated in all patients. The most common clinical onset was rapidly progressive cognitive decline, followed by focal neurological signs. Brain CT/MR showed unenhanced expansive subcortical lesions, corresponding to areas of vasogenic edema, associated with chronic lobar, cortical, or cortical–subcortical micro/macrohemorrhages. Clinical symptoms recovered in a few weeks under treatment in eight patients and spontaneously in the remaining two. MRI follow-up at 2 to 12 months after treatment showed resolution of the lesions. Three patients experienced symptomatic disease recurrence, with new lesions on CT/MR. In the absence of histological data, early recognition of the clinical symptoms and typical radiologic features of CAA-related inflammation is essential to enable timely establishment of proper treatment.

BACKGROUND: There is currently no clinical imaging technique available to assess the degree of inflammation associated with atherosclerotic plaques. This study aims to develop targeted superparamagnetic particles of iron oxide (SPIO) as a magnetic resonance imaging (MRI) probe for detecting inflamed endothelial cells. METHODS: The in vitro study consists of the characterisation and detection of inflammatory markers on activated endothelial cells by immunocytochemistry and MRI using biotinylated anti-P-selectin and anti-VCAM-1 (vascular cell adhesion molecule 1) antibody and streptavidin conjugated SPIO. RESULTS: Established an in vitro cellular model of endothelial inflammation induced with TNF-α (tumor necrosis factor alpha). Inflammation of endothelial cells was confirmed with both immunocytochemistry and MRI. These results revealed both a temporal and dose dependent expression of the inflammatory markers, P-selectin and VCAM-1, on exposure to TNF-α. CONCLUSION: This study has demonstrated the development of an in vitro model to characterise and detect inflamed endothelial cells by immunocytochemistry and MRI. This will allow the future development of contrast agents and protocols for imaging vascular inflammation in atherosclerosis. This work may form the basis for a translational study to provide clinicians with a novel tool for the in vivo assessment of atherosclerosis.

Sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) is a ligand of inflammation-inducible vascular adhesion protein-1 (VAP-1). We compared 68Ga-DOTA- and 18F-fluorodeoxyribose- (FDR-) labeled Siglec-9 motif peptides for PET imaging of inflammation. Methods. Firstly, we examined 68Ga-DOTA-Siglec-9 and 18F-FDR-Siglec-9 in rats with skin/muscle inflammation. We then studied 18F-FDR-Siglec-9 for the detection of inflamed atherosclerotic plaques in mice and compared it with previous 68Ga-DOTA-Siglec-9 results. Lastly, we estimated human radiation dosimetry from the rat data. Results. In rats, 68Ga-DOTA-Siglec-9 (SUV, 0.88±0.087) and 18F-FDR-Siglec-9 (SUV, 0.77±0.22) showed comparable (P=0.29) imaging of inflammation. In atherosclerotic mice, 18F-FDR-Siglec-9 detected inflamed plaques with a target-to-background ratio (1.6±0.078) similar to previously tested 68Ga-DOTA-Siglec-9 (P=0.35). Human effective dose estimates for 68Ga-DOTA-Siglec-9 and 18F-FDR-Siglec-9 were 0.024 and 0.022 mSv/MBq, respectively. Conclusion. Both tracers are suitable for PET imaging of inflammation. The easier production and lower cost of 68Ga-DOTA-Siglec-9 present advantages over 18F-FDR-Siglec-9, indicating it as a primary choice for clinical studies.

Molecular imaging is defined as the in vivo measurement of biological processes at the cellular and molecular levels [1]. The technique visualizes pathophysiologic processes noninvasively in real time, with the potential for serial monitoring, and provides information regarding specific molecular alterations underlying the disease status of individual subjects. By complementing conventional “anatomical or physiological” imaging, molecular imaging enables early detection of disease, staging of disease, and quantitative assessment of therapeutic response. Molecular imaging also contributes to the understanding of stroke pathophysiology in living animals and humans. This chapter describes the principles and methods of molecular imaging techniques, while providing a translational perspective in stroke.

The aim of this overview article is to present the current possibilities of radionuclide scintigraphic small intestine imaging. Nuclear medicine has a few methods—scintigraphy with red blood cells labelled by means ofTc99mfor detection of the source of bleeding in the small intestine, Meckel’s diverticulum scintigraphy for detection of the ectopic gastric mucosa, radionuclide somatostatin receptor imaging for carcinoid, and radionuclide inflammation imaging. Video capsule or deep enteroscopy is the method of choice for detection of most lesions in the small intestine. Small intestine scintigraphies are only a complementary imaging method and can be successful, for example, for the detection of the bleeding site in the small intestine, ectopic gastric mucosa, carcinoid and its metastasis, or inflammation. Radionuclide scintigraphic small intestine imaging is an effective imaging modality in the localisation of small intestine lesions for patients in whom other diagnostic tests have failed to locate any lesions or are not available.

Interleukin-2 (IL2) binds with high affinity to the IL2 receptors overexpressed on activated T lymphocytes in various pathologic conditions. Radiolabeling of IL2 with a positron-emitting isotope could provide a tool for noninvasive PET of activated T cells in immune-mediated diseases. We report the labeling of IL2 with N-succinimidyl 4-F-18-fluorolbenzoate (F-18-SFB) for the synthesis of N-(4-F-18-fluorobenzoyl)interleukin-2 (F-18-FB-IL2) and the in vitro and in vivo evaluation of this novel radiopharmaceutical for the detection of IL2 receptor-positive cells by PET. Methods: F-18-SFB was efficiently prepared using a 3-step radiochemical pathway. Purified F-18-SFB was incubated with IL2 in borate buffer (pH 8.5) and ethanol at 50 degrees C for 10 min. F-18-FB-IL2 was purified by reversed-phase high-performance liquid chromatography. As in vitro quality controls, a biologic binding assay, sodium dodecyl sulfate polyacrylamide gel electrophoresis, mass spectrometry, and 3-chloroacetic acid precipitation stability tests were performed. Biodistribution studies were performed in BALB/c mice to evaluate the distribution of the tracer in healthy animals. PET experiments were performed in severe combined immunodeficiency disease mice inoculated with phytohemoagglutinin-activated human peripheral blood mononuclear cells (hPBMc). Whole-body images were acquired 30 min after injection of 5-15 MBq of F-18-FB-IL2. Results: F-18-SFB was produced with a 34%-38% radiochemical yield. The radiochemical purity after solid-phase extraction purification ranged from 93% to 96%. Conjugation of F-18-SFB to IL2 yielded F-18-FB-IL2 as the major product. The radiochemical yield of F-18-FB-IL2 after high-performance liquid chromatography purification was 25%-35% based on F-18-SFB. F-18-FB-IL2 was stable in plasma at 37 degrees C and capable of stimulating T cells to an extent similar to native IL2. A biodistribution study showed highest tracer uptake in the kidneys and bladder due to rapid renal clearance of the tracer. Small-animal PET images showed binding of F-18-FB-IL2 to activated hPBMc proportional to the number of injected cells. Conclusion: We report the successful labeling of IL2 with F-18 for PET of activated T lymphocytes. F-18-FB-IL2 is stable, is biologically active, and allows in vivo detection of activated T lymphocytes.

This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s12574-010-0051-z., Background: Reports on ultrasound inflammation imaging with non-specific targeted microbubbles in the heart have been scarce. We investigated whether inflammation induced by myocardial ischemia-reperfusion in rats could be evaluated by ultrasound inflammation imaging with non-specific targeted microbubbles. Methods: Six rats subjected to 30 min of occlusion of the left anterior descending artery (LAD) followed by 4 h of reperfusion (ischemia group) and 4 rats subjected to the sham operation (sham group) were used. Ultrasound inflammation imaging was performed 4 h after reperfusion, and non-circulating signal intensity (SI), which reflects the signal derived from microbubbles phagocytosed by neutrophils in inflamed tissue, was calculated by the SI difference between the initial and subsequent imaging both in the LAD and non-LAD areas. The accumulation of neutrophils was confirmed by myeloperoxidase (MPO) staining. Results: Non-circulating SI in the LAD area was significantly greater for the ischemia group than the sham group [5.19 ± 2.19 (ischemia) vs. 0.31 ± 0.13 (sham) dB, p < 0.01]. Non-circulating SI in the LAD area was significantly higher than that in the non-LAD area when compared in the same rat of the ischemia group [5.19 ± 2.19 (LAD) vs. 0.18 ± 0.64 (non-LAD) dB, p < 0.01]. MPO-positive cells were confirmed in the LAD area of the ischemia group. Conclusion: Inflammation induced by myocardial ischemia-reperfusion in rats could be quantitatively assessed by ultrasound inflammation imaging with non-specific targeted microbubbles.

Inflammation is important at many stages of atherosclerotic plaque development. We highlight several imaging modalities that can quantify the degree of plaque inflammation noninvasively. Imaging of this type might allow testing of novel antiatherosclerosis drugs, identification of patients at risk of plaque rupture, and deeper insight into the biology of the disease. The imaging modalities are discussed in relation to their potential use in these areas.

Small synthetic receptor-binding peptides are the agents of choice for diagnostic imaging and radiotherapy of cancers due to their favorable pharmacokinetics. Molecular modification techniques permit the synthesis of a variety of bioactive peptides with chelating groups, without compromising biological properties. Various techniques have been developed that allow efficient and site-specific labeling of peptides with clinically useful radionuclides such as (99m)Tc, (123)I, (111)In, and (18)F. Among them, (99m)Tc is the radionuclide of choice because of its excellent chemical and imaging characteristics. Recently, many (99m)Tc-labeled peptides have proven to be useful imaging agents. Beside (99m)Tc-labeled peptides, several peptides radiolabeled with (111)In and (123)I have been prepared and characterized. In addition, (18)F-labeled peptides hold clinical potential due to their ability to quantitatively detect and characterize a variety of human diseases using positron-emission tomography. The availability of this wide range of peptides labeled with different radionuclides offers multiple diagnostic and therapeutic applications. Various receptors are over-expressed in particular tumor types and peptides binding to these receptors can be used to visualize tumor lesions scintigraphically. Thus, radiolabeled peptides have potential use as carriers for the delivery of radionuclides to tumors, infarcts, and infected tissues for diagnostic imaging and radiotherapy. Many radiolabeled peptides are currently under investigation to determine their potential as imaging agents. These peptides are designed mainly for thrombus, tumor, and infection/inflammation imaging. This article presents recent developments in small synthetic peptides for imaging of thrombosis, tumors, and infection/inflammation.

While depiction and definition of morphological and architectural characteristics of CNS vascular disorders remains the first step of an MR analysis, emerging imaging techniques offer new functional information that might help to characterize rupture risk of CNS vascular disorders. Two main orientations are suggested by recent studies: inflammation of the vessel wall and analysis of physical constraints of blood flow using 4D flow imaging (shear parietal). This paper will focus on radiological application of 4D flow imaging and inflammation imaging, in the characterization of potential prognostic markers of CNS vascular disorders. We will review the basic technical considerations of 4D flow MRA, inflammation imaging and discuss their applications in CNS vascular disorders: aneurysms, arteriovenous malformation, dural arteriovenous fistulas. We will illustrate their potential in the development of individual rupture risk criteria in brain vascular disorders.

To evaluate the use of a recently developed fast-clearing ultrasmall superparamagnetic iron oxide (USPIO) for detection of vascular inflammation in atherosclerotic plaque.The study protocol was approved by the animal experimentation ethics committee. A recently introduced USPIO, P904, and a reference-standard USPIO, ferumoxtran-10, were tested in a rabbit model of induced aortic atherosclerosis. In vivo magnetic resonance (MR) angiography and T2*-weighted plaque MR imaging were performed at baseline and after administration of P904 and ferumoxtran-10 (administered dose for both, 1000 micromol of iron per kilogram of body weight) in 26 hyperlipidemic New Zealand white rabbits. The variation in vessel wall area over time was evaluated with nonparametric testing. Ex vivo MR imaging findings were compared with iron content at linear regression analysis.With in vivo MR imaging, plaque analysis was possible as early as 24 hours after P904 injection. The authors observed a 27.75% increase in vessel wall area due to susceptibility artifacts on day 2 (P = .04) and a 38.81% increase on day 3 (P = .04) after P904 administration compared with a 44.5% increase in vessel wall area on day 7 (P = .04) and a 34.8% increase on day 10 (P = .22) after ferumoxtran-10 administration. These susceptibility artifacts were correlated with intraplaque iron uptake in the corresponding histologic slices. The number of pixels with signal loss on the ex vivo MR images was linearly correlated with the logarithm of the iron concentration (P = .0001; R(2) = 0.93).Plaque inflammation in rabbits can be detected earlier with P904 than with ferumoxtran-10 owing to the faster blood pharmacokinetics and the early uptake of P904 in the reticuloendothelial system.http://radiology.rsnajnls.org/cgi/content/full/252/2/401/DC1.

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine that may play a role in the pathogenesis of inflammation. Radiolabeled anti-MIF McAb can be used to detect in vivo inflammatory changes. The objective of this study was to investigate in vivo biology of radioiodinated anti-MIF McAb using the inflammation model mice. Anti-MIF McAb was radioiodinated with Na125I by Iodogen method. Animal models were induced in the mice by intramuscular injection ofS. aureus,E. coli, and turpentine oil. The biodistribution studies with radioiodinated anti-MIF McAb were performed on inflammation mice. The relationship between inflammatory lesions and anti-MIF McAb binding was investigated using the percent of injected dose per gram tissue (% ID/g) of tissue samples and whole-body autoradiography. The radioactivity of125I-anti-MIF McAb in the inflammatory tissue increased gradually for three inflammation models. The highest uptake was found inS. aureusgroup and the lowest was inE. coligroup. The uptake in turpentine oil group was average. Whole-body autoradiography showed that all inflammation foci could be visualized clearly from 24 hours after injection, but 48 hours images were much clearer in accordance with the high T/NT ratio. These results demonstrate the ability of radioiodinated anti-MIF McAb to measure in vivo inflammatory events represented by high expression of MIF and suggests that radiolabeled anti-MIF McAb warrants further investigation as a potential inflammation-seeking agent for imaging to detect inflammatory disorders.

Barium concretions are a rare complication of barium administration resulting from prolonged retention of the barium within the bowel. Indium-111 white blood cell localization studies are a sensitive and specific indicator of inflammation. Indium-111 white blood cell localization was noted

Series Editor: Zahi Fayad Molecular Imaging of Cardiovascular Disease ATVB In Focus Articles in this series: •Choudhury RP, Fisher EA. Molecular imaging in atherosclerosis, thrombosis, and vascular inflammation. Arterioscler Thromb Vasc Biol . 2009;29:983–991. •Cormode DP, Skajaa T, Fayad ZA, Mulder WJM. Nanotechnology in medical imaging: probe design and applications. Arterioscler Thromb Vasc Biol . 2009;29:992–1000. •Tang TY, Muller KH, Graves MJ, Li ZY, Walsh SR, Young V, Sadat U, Howarth SPS, Gillard JH. Iron oxide particles for atheroma imaging. Arterioscler Thromb Vasc Biol . 2009;29:1001–1008. •Rudd JHF, Hyafil F, Fayad ZA. Inflammation imaging in atherosclerosis. Arterioscler Thromb Vasc Biol . 2009;29:1009–1016. •Jaffer FA, Libby P, Weissleder R. Optical and multimodality molecular imaging: insights into atherosclerosis. Arterioscler Thromb Vasc Biol. 2009;29:1017–1024. •Kraitchman DL, Bulte JWM. In vivo imaging of stem cells and beta cells using direct cell labeling and reporter gene methods. Arterioscler Thromb Vasc Biol . 2009;29:1025–1030. •Laufer EM, Winkens MHM, Narula J, Hofstra L. Imaging of cell death in atherosclerosis. Arterioscler Thromb Vasc Biol . 2009;29:1031–1038. Molecular imaging is defined today as the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems, and molecular imaging agents are probes …

Determination of the localization of acute, subacute and chronic infectious foci may have important implications for the management of patients. Imaging techniques like ultrasound, CT-scanning or MRI are in most cases unable to discriminate active processes from scar tissue due to a cured infection or after surgery. In contrast, scintigraphic images are not determined morphologically, they are based on physiochemical processes in tissues. In clinical practice not only the presence of an active inflammatory process, but also the localization and the number of foci needs to be determined; scintigraphic imaging is an excellent noninvasive method of whole-body scanning. In clinical practice several radiopharmaceuticals are used to image foci of infection and inflammation. In this chapter the development and the potential of a liposome-based radiopharmaceutical for infection and inflammation imaging is described and compared with conventional radiopharmaceuticals.

A new agent originally introduced for localizing inflammatory lesions is Tc-99m human immunoglobulin G (HIG). Recently, focal uptake of this agent was seen in malignant lesions in a limited number of patients during inflammation imaging studies. In this prospective clinical study, the authors aimed to evaluate the uptake of Tc-99m HIG in malignant lesions. Nineteen patients with histopathologically proven malignant tumors were studied (seven had distant metastases, the primary tumor was surgically removed in two). There was no evidence of inflammation or infection in any patient. The authors imaged patients at 1, 4, and 24 hours after injection. The dose was 15-20 mCi (555-740 MBq). Focal uptake was detected in the primary tumor in six patients and in the metastases in five patients, raising some question about the specificity of Tc-99m HIG imaging for the detection of inflammation and infection.

Tc-99m dextran has been shown to have inflammation imaging capability. Two cases are presented: one with Meckel's diverticulum and another with osteomyelitis. In both, the agent correctly identified the abnormal sites. It appeared to be better than Tc-99m pertechnetate and Tc-99m MDP in these conditions. Its nonprotein nature, easy and stable tagging, and good target-to-nontarget ratio make it a practical inflammation imaging radiotracer.

Leukocytes labeled with technetium-99m hexamethylpropyleneamine oxime (HMPAO) were used in 100 patients: 32 with suspected inflammatory bowel disease, 17 with fever of unknown origin, 21 with suspected abdominal sepsis, 20 with suspected bone sepsis, seven with bronchiectasis, and three with recent myocardial infarction. The distribution of activity in patients subsequently shown not to have inflammatory bowel disease was similar to that previously described for indium-111-labeled leukocytes. However, in this study, activity was also seen in the kidneys and bladder and occasionally the gallbladder on both early (1-3 hours) and late (24 hours) views, and in the colon in late views. Migration of Tc-99m-labeled granulocytes was seen in inflammatory disease as early as 30 minutes after injection, while normal bowel activity was not seen before 4 hours. The sensitivity of Tc99m-labeled leukocytes in the detection of inflammation was 100%, the specificity was 95%.

Item does not contain fulltext Scintigraphic imaging of infection and inflammation is a powerful diagnostic tool in the management of patients with infectious or inflammatory diseases. Most infectious and inflammatory foci can be visualized accurately with radiolabeled autologous leukocytes. However, preparation of this radiopharmaceutical is laborious and requires the handling of potentially contaminated blood. Nowadays, a few radiopharmaceuticals are available that could replace radiolabeled leukocytes, such as: 67Ga-citrate, 99mTc-IgG and 99mTc-labeled antigranulocyte antibody preparations. Furthermore, various agents labeled with 99mTc are currently developed for this application: chemotactic peptides, cytokines and liposomes. Here, the characteristics and the diagnostic potential of established and experimental radiopharmaceuticals for infection and inflammation imaging are reviewed.

Atherosclerosis is an inflammatory disease of large and medium-sized arteries, characterized by the growth of atherosclerotic lesions (plaques). These plaques often develop at inner curvatures of arteries, branchpoints, and bifurcations, where the endothelial wall shear stress is low and oscillatory. In conjunction with other processes such as lipid deposition, biomechanical factors lead to local vascular inflammation and plaque growth. There is also evidence that low and oscillatory shear stress contribute to arterial remodeling, entailing a loss in arterial elasticity and, therefore, an increased pulse-wave velocity. Although altered shear stress profiles, elasticity and inflammation are closely intertwined and critical for plaque growth, preclinical and clinical investigations for atherosclerosis mostly focus on the investigation of one of these parameters only due to the experimental limitations. However, cardiovascular magnetic resonance imaging (MRI) has been demonstrated to be a potent tool which can be used to provide insights into a large range of biological parameters in one experimental session. It enables the evaluation of the dynamic process of atherosclerotic lesion formation without the need for harmful radiation. Flow-sensitive MRI provides the assessment of hemodynamic parameters such as wall shear stress and pulse wave velocity which may replace invasive and radiation-based techniques for imaging of the vascular function and the characterization of early plaque development. In combination with inflammation imaging, the analyses and correlations of these parameters could not only significantly advance basic preclinical investigations of atherosclerotic lesion formation and progression, but also the diagnostic clinical evaluation for early identification of high-risk plaques, which are prone to rupture. In this review, we summarize the key applications of magnetic resonance imaging for the evaluation of plaque characteristics through flow sensitive and morphological measurements. The simultaneous measurements of functional and structural parameters will further preclinical research on atherosclerosis and has the potential to fundamentally improve the detection of inflammation and vulnerable plaques in patients.

Background Vascular adhesion protein-1 (VAP-1) is an adhesion molecule that plays a key role in recruiting leucocytes into sites of inflammation. We have previously shown that 68Gallium-labelled VAP-1-targeting peptide (68Ga-DOTAVAP-P1) is a positron emission tomography (PET) imaging agent, capable of visualising inflammation in rats, but disadvantaged by its short metabolic half-life and rapid clearance. We hypothesised that prolonging the metabolic half-life of 68Ga-DOTAVAP-P1 could further improve its imaging characteristics. In this study, we evaluated a new analogue of 68Ga-DOTAVAP-P1 modified with a mini-polyethylene glycol (PEG) spacer (68Ga-DOTAVAP-PEG-P1) for in vivo imaging of inflammation. Methods Whole-body distribution kinetics and visualisation of inflammation in a rat model by the peptides 68Ga-DOTAVAP-P1 and 68Ga-DOTAVAP-PEG-P1 were evaluated in vivo by dynamic PET imaging and ex vivo by measuring the radioactivity of excised tissues. In addition, plasma samples were analysed by radio-HPLC for the in vivo stability of the peptides. Results The peptide with the mini-PEG spacer showed slower renal excretion but similar liver uptake as the original peptide. At 60 min after injection, the standardised uptake value of the inflammation site was 0.33 ± 0.07 for 68Ga-DOTAVAP-P1 and 0.53 ± 0.01 for 68Ga-DOTAVAP-PEG-P1 by PET. In addition, inflammation-to-muscle ratios were 6.7 ± 1.3 and 7.3 ± 2.1 for 68Ga-DOTAVAP-P1 and 68Ga-DOTAVAP-PEG-P1, respectively. The proportion of unchanged peptide in circulation at 60 min after injection was significantly higher for 68Ga-DOTAVAP-PEG-P1 (76%) than for 68Ga-DOTAVAP-P1 (19%). Conclusion The eight-carbon mini-PEG spacer prolonged the metabolic half-life of the 68Ga-DOTAVAP-P1 peptide, leading to higher target-to-background ratios and improved in vivo PET imaging of inflammation.