scholarly journals Improved Detection of Molecular Markers of Atherosclerotic Plaques Using Sub-Millimeter PET Imaging

Molecules ◽  
2020 ◽  
Vol 25 (8) ◽  
pp. 1838 ◽  
Author(s):  
Jessica Bridoux ◽  
Sara Neyt ◽  
Pieterjan Debie ◽  
Benedicte Descamps ◽  
Nick Devoogdt ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Ex Vivo ◽  
High Sensitivity ◽  
Radiochemical Yield ◽  
Control Group ◽  
Complexing Agent ◽  
Atherosclerotic Plaques ◽  
Atherosclerotic Lesions ◽  
Pet Ct

Since atherosclerotic plaques are small and sparse, their non-invasive detection via PET imaging requires both highly specific radiotracers as well as imaging systems with high sensitivity and resolution. This study aimed to assess the targeting and biodistribution of a novel fluorine-18 anti-VCAM-1 Nanobody (Nb), and to investigate whether sub-millimetre resolution PET imaging could improve detectability of plaques in mice. The anti-VCAM-1 Nb functionalised with the novel restrained complexing agent (RESCA) chelator was labelled with [18F]AlF with a high radiochemical yield (>75%) and radiochemical purity (>99%). Subsequently, [18F]AlF(RESCA)-cAbVCAM1-5 was injected in ApoE−/− mice, or co-injected with excess of unlabelled Nb (control group). Mice were imaged sequentially using a cross-over design on two different commercially available PET/CT systems and finally sacrificed for ex vivo analysis. Both the PET/CT images and ex vivo data showed specific uptake of [18F]AlF(RESCA)-cAbVCAM1-5 in atherosclerotic lesions. Non-specific bone uptake was also noticeable, most probably due to in vivo defluorination. Image analysis yielded higher target-to-heart and target-to-brain ratios with the β-CUBE (MOLECUBES) PET scanner, demonstrating that preclinical detection of atherosclerotic lesions could be improved using the latest PET technology.

scholarly journals Biodistribution of Nanostructured Lipid Carriers in Mice Atherosclerotic Model

Molecules ◽  
2019 ◽  
Vol 24 (19) ◽  
pp. 3499 ◽  
Author(s):  
Devel ◽  
Almer ◽  
Cabella ◽  
Beau ◽  
Bernes ◽  
...  
Keyword(s):  
Colloidal Stability ◽  
Ex Vivo ◽  
Particle Diameter ◽  
Nanostructured Lipid Carriers ◽  
Atherosclerotic Plaques ◽  
Particle Uptake ◽  
Atherosclerotic Lesions ◽  
Physico Chemical

Atherosclerosis is a major cardiovascular disease worldwide, that could benefit from innovative nanomedicine imaging tools and treatments. In this perspective, we here studied, by fluorescence imaging in ApoE-/- mice, the biodistribution of non-functionalized and RXP470.1-targeted nanostructured lipid carriers (NLC) loaded with DiD dye. RXP470.1 specifically binds to MMP12, a metalloprotease that is over-expressed by macrophages residing in atherosclerotic plaques. Physico-chemical characterizations showed that RXP-NLC (about 105 RXP470.1 moieties/particle) displayed similar features as non-functionalized NLC in terms of particle diameter (about 60-65 nm), surface charge (about −5 — −10 mV), and colloidal stability. In vitro inhibition assays demonstrated that RXP-NLC conserved a selectivity and affinity profile, which favored MMP-12. In vivo data indicated that NLC and RXP-NLC presented prolonged blood circulation and accumulation in atherosclerotic lesions in a few hours. Twenty-four hours after injection, particle uptake in atherosclerotic plaques of the brachiocephalic artery was similar for both nanoparticles, as assessed by ex vivo imaging. This suggests that the RXP470.1 coating did not significantly induce an active targeting of the nanoparticles within the plaques. Overall, NLCs appeared to be very promising nanovectors to efficiently and specifically deliver imaging agents or drugs in atherosclerotic lesions, opening avenues for new nanomedicine strategies for cardiovascular diseases.

scholarly journals A Semi Rigid Novel Hydroxamate AMPED-Based Ligand for 89Zr PET Imaging

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5819
Author(s):  
Lisa Russelli ◽  
Francesco De Rose ◽  
Loredana Leone ◽  
Sybille Reder ◽  
Markus Schwaiger ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Ex Vivo ◽  
Small Animal ◽  
Biologically Active ◽  
Small Animal Pet ◽  
Organ Distribution ◽  
Complexing Agent ◽  
Distribution Studies

In this work, we designed, developed, characterized, and investigated a new chelator and its bifunctional derivative for 89Zr labeling and PET-imaging. In a preliminary study, we synthesized two hexadentate chelators named AAZTHAS and AAZTHAG, based on the seven-membered heterocycle AMPED (6-amino-6-methylperhydro-1,4-diazepine) with the aim to increase the rigidity of the 89Zr complex by using N-methyl-N-(hydroxy)succinamide or N-methyl-N-(hydroxy)glutaramide pendant arms attached to the cyclic structure. N-methylhydroxamate groups are the donor groups chosen to efficiently coordinate 89Zr. After in vitro stability tests, we selected the chelator with longer arms, AAZTHAG, as the best complexing agent for 89Zr presenting a stability of 86.4 ± 5.5% in human serum (HS) for at least 72 h. Small animal PET/CT static scans acquired at different time points (up to 24 h) and ex vivo organ distribution studies were then carried out in healthy nude mice (n = 3) to investigate the stability and biodistribution in vivo of this new 89Zr-based complex. High stability in vivo, with low accumulation of free 89Zr in bones and kidneys, was measured. Furthermore, an activated ester functionalized version of AAZTHAG was synthesized to allow the conjugation with biomolecules such as antibodies. The bifunctional chelator was then conjugated to the human anti-HER2 monoclonal antibody Trastuzumab (Tz) as a proof of principle test of conjugation to biologically active molecules. The final 89Zr labeled compound was characterized via radio-HPLC and SDS-PAGE followed by autoradiography, and its stability in different solutions was assessed for at least 4 days.

scholarly journals Amyloid-Targeting PET Tracer [18F]Flutemetamol Accumulates in Atherosclerotic Plaques

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1072 ◽  
Author(s):  
Sanna Hellberg ◽  
Johanna Silvola ◽  
Heidi Liljenbäck ◽  
Max Kiugel ◽  
Olli Eskola ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Mouse Strains ◽  
Aortic Tissue ◽  
Atherosclerotic Plaques ◽  
Carotid Artery Plaque ◽  
Pet Tracer ◽  
Pet Ct ◽  
Human Carotid

Atherosclerosis is characterized by the accumulation of oxidized lipids in the artery wall, which triggers an inflammatory response. Oxidized low-density lipoprotein (ox-LDL) presents amyloid-like structural properties, and different amyloid species have recently been recognized in atherosclerotic plaques. Therefore, we studied the uptake of the amyloid imaging agent [18F]Flutemetamol in atherosclerotic plaques. The binding of [18F]Flutemetamol to human carotid artery plaque was studied in vitro. In vivo uptake of the tracer was studied in hypercholesterolemic IGF-II/LDLR−/−ApoB100/100 mice and C57BL/6N controls. Tracer biodistribution was studied in vivo with PET/CT, and ex vivo by gamma counter and digital ex vivo autoradiography. The presence of amyloid, ox-LDL, and macrophages in the plaques was examined by immunohistochemistry. [18F]Flutemetamol showed specific accumulation in human carotid plaque, especially in areas positive for amyloid beta. The aortas of IGF-II/LDLR−/−ApoB100/100 mice showed large thioflavin-S-positive atherosclerotic plaques containing ox-LDL and macrophages. Autoradiography revealed 1.7-fold higher uptake in the plaques than in a lesion-free vessel wall, but no difference in aortic tissue uptake between mouse strains were observed in the in vivo PET/CT. In conclusion, [18F]Flutemetamol binds to amyloid-positive areas in human atherosclerotic plaques. Further studies are warranted to clarify the uptake mechanisms, and the potential of the tracer for in vivo imaging of atherosclerosis in patients.

Abstract 15108: Imaging Coronary Atherosclerosis Using [18F]FDG PET-CT: Validation Study in Pigs

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Miikka Tarkia ◽  
Antti Saraste ◽  
Christoffer Stark ◽  
Tommi Vähäsilta ◽  
Timo Savunen ◽  
...  
Keyword(s):  
Coronary Arteries ◽  
Coronary Atherosclerosis ◽  
Vessel Wall ◽  
Ex Vivo ◽  
Intimal Thickening ◽  
Fdg Uptake ◽  
Atherosclerotic Lesions ◽  
Pet Ct ◽  
18F Fdg

Introduction: Positron emission tomography (PET) with 18F-fluorodeoxyglucose ([18F]FDG) can be used to detect atherosclerotic plaque inflammation. The degree of [18F]FDG uptake in different stages of coronary atherosclerosis remains largely unknown. Thus, we studied the amount of [18F]FDG uptake and feasibility of its in vivo quantification by combination of PET and computed tomography angiography (CTA) in a pig model of atherosclerosis. Methods: In order to induce coronary atherosclerosis, diabetes was caused by streptozotocin injections in farm pigs (n=10). After 6 months on high-fat diet, pigs underwent dual gated cardiac PET and CTA to measure [18F]FDG uptake in the proximal segments of coronary arteries as maximal target to background ratio (TBR = [18F]FDG uptake normalized to blood pool). Proximal coronary segments (n=33) were harvested for ex vivo measurement of radioactivity and for histology and measurement of tracer uptake into the vessel wall by autoradiography (ARG). Results: The pigs were hyperglycemic (12.3±4.7 mmol/L) and hypercholesterolemic (12.7±5.1 mmol/L) at the end of the study. The coronary arteries showed intimal thickening (n=16 segments) and atheroma (n=10 segments). Compared with the normal vessel wall, ARG showed 1.7±0.7 times higher accumulation of [18F]FDG in intimal thickening and 4.1±2.3 in atheroma (p=0.004 and p=0.003, respectively). Ex vivo mean vessel to blood ratio of segments with atheroma was higher than non-atherosclerotic segments (2.6±1.2 vs. 1.3±0.7, p=0.04). In vivo PET imaging showed the highest TBR of 2.7. However, maximal TBR was not significantly different in segments without atherosclerosis (1.1±0.5) and either intimal thickening (1.2±0.4, p=1.0) or atheroma (1.6±0.6, p=0.4) and no correlation was seen between the segmental TBR measured by in vivo PET-CT and [18F]FDG uptake measured by either biodistribution or autoradiography. Conclusions: We found increased [18F]FDG uptake in atherosclerotic lesions. However, quantification of [18F]FDG uptake in these relatively small and early stage atherosclerotic lesions by dual gated PET and CTA was not feasible. Further studies are needed to clarify feasibility of this approach in more advanced and highly inflamed atherosclerotic coronary plaques.

scholarly journals Synthesis of a novel 89Zr labeled HER2 affibody and its application study in tumor PET imaging

2020 ◽  
Author(s):  
Yuping Xu ◽  
Lizhen Wang ◽  
Donghui Pan ◽  
Junjie Yan ◽  
Xinyu Wang ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Radiochemical Purity ◽  
Ex Vivo ◽  
Radiochemical Yield ◽  
Immunohistochemical Analysis ◽  
In Vivo Studies ◽  
Potential Candidate ◽  
Synthesis Time ◽  
Normal Tissues

Abstract Background: Human epidermal growth factor receptor-2 (HER2) is an essential biomarker for tumor treatment. Affibody is an ideal vector for preparing HER2 specific probes because of high affinity and rapid clearance from normal tissues etc. Zirconium-89 is a PET imaging isotope with a long half-life and suitable for monitoring biological processes for more extended periods. In this study, a novel 89 Zr-labeled HER2 affibody, [ 89 Zr]Zr-DFO-MAL-Cys-MZHER2, was synthesized, and its imaging characters were also assessed. Results: The precursor, DFO-MAL-Cys-MZHER2, was obtained with a yield of nearly 50%. The radiochemical yield of [ 89 Zr]Zr -DFO-MAL-Cys-MZHER2 was 90.2±1.9% , and the radiochemical purity was higher than 95%. The total synthesis time was only 30 minutes. The probe was stable in PBS and serum. The tracer accumulated in HER2 overexpressing human ovarian cancer SKOV-3 cells. In vivo studies in mice bearing tumors showed that the probe highly retained in SKOV-3 xenografts even for 48 hours. The tumors were visualized with good contrast to normal tissues. ROI analysis revealed that the average uptake values in the tumor were greater than 5%IA/g during 48 hours postinjection. On the contrary, the counterparts of MCF-7 tumors kept low levels（~1%IA/g）. The outcome was consistent with the immunohistochemical analysis and ex vivo autoradiography. The probe quickly cleared from the normal organs except kidneys and mainly excreted through the urinary system. Conclusion: The novel HER2 affibody for PET imaging was easily prepared with satisfactory labeling yield and radiochemical purity. [ 89 Zr]Zr-DFO-MAL-Cys-MZHER2 is a potential candidate for detecting HER2 expression. It may play specific roles in clinical cancer theranostics.

scholarly journals Synthesis of a novel 89Zr labeled HER2 affibody and its application study in tumor PET imaging

2020 ◽  
Author(s):  
Yuping Xu ◽  
Lizhen Wang ◽  
Donghui Pan ◽  
Junjie Yan ◽  
Xinyu Wang ◽  
...  
Keyword(s):  
Pet Imaging ◽  
Radiochemical Purity ◽  
Ex Vivo ◽  
Radiochemical Yield ◽  
Immunohistochemical Analysis ◽  
In Vivo Studies ◽  
Potential Candidate ◽  
Synthesis Time ◽  
Normal Tissues

Abstract Background: Human epidermal growth factor receptor-2 (HER2) is an essential biomarker for tumor treatment. Affibody is an ideal vector for preparing HER2 specific probes because of high affinity and rapid clearance from normal tissues etc. Zirconium-89 is a PET imaging isotope with a long half-life and suitable for monitoring biological processes for more extended periods. In this study, a novel 89Zr-labeled HER2 affibody, [89Zr]Zr-DFO-MAL-Cys-MZHER2, was synthesized, and its imaging characters were also assessed. Results: The precursor, DFO-MAL-Cys-MZHER2, was obtained with a yield of nearly 50%. The radiochemical yield of [89Zr]Zr -DFO-MAL-Cys-MZHER2 was 90.2±1.9% , and the radiochemical purity was higher than 95%. The total synthesis time was only 30 minutes. The probe was stable in PBS and serum. The tracer accumulated in HER2 overexpressing human ovarian cancer SKOV-3 cells. In vivo studies in mice bearing tumors showed that the probe highly retained in SKOV-3 xenografts even for 48 hours. The tumors were visualized with good contrast to normal tissues. ROI analysis revealed that the average uptake values in the tumor were greater than 5%IA/g during 48 hours postinjection. On the contrary, the counterparts of MCF-7 tumors kept low levels（~1%IA/g）. The outcome was consistent with the immunohistochemical analysis and ex vivo autoradiography. The probe quickly cleared from the normal organs except kidneys and mainly excreted through the urinary system. Conclusion: The novel HER2 affibody for PET imaging was easily prepared with satisfactory labeling yield and radiochemical purity. [89Zr]Zr-DFO-MAL-Cys-MZHER2 is a potential candidate for detecting HER2 expression. It may play specific roles in clinical cancer theranostics.

Abstract 5788: VCAM-1 Targeted PET-CT Detects Inflammatory Atherosclerotic Plaques

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Matthias Nahrendorf ◽  
Edmund Keliher ◽  
Peter Panizzi ◽  
Hanwen Zhang ◽  
Sheena Hembrador ◽  
...  
Keyword(s):  
Dynamic Range ◽  
Atherosclerotic Lesion ◽  
Vascular Anatomy ◽  
High Sensitivity ◽  
Ct Imaging ◽  
Atherosclerotic Plaques ◽  
Mrna Levels ◽  
Pet Ct

Hybrid PET-CT imaging of VCAM-1 expression and vascular anatomy may facilitate simultaneous assessment of atherosclerotic lesion biology and morphology, and enhance risk assessment in individual patients. We used combined in vitro/in vivo screening of candidate affinity ligands and developed a PET reporter for imaging VCAM-1 expression with high sensitivity, specificity and translational potential. Three different phage display-derived VCAM-1 affinity peptides were tested using immobilized VCAM-1, VCAM-1 expressing cells and apoE−/− mice. A compound with a linear peptide and arborising tetrameric design showed high affinity (86.6 nM) and specificity for VCAM-1 (97% inhibition with soluble VCAM-1). This lead compound was derivatized with 18Fluorine to synthesize the clinically viable PET agent 18F-4V. In vivo PET-CT imaging showed robust uptake of 18F-4V in plaque laden arterial sections from 8 apoE−/− mice, significantly higher than in 4 wild type mice and attenuated by atorvastatin treatment (p<0.05). 18F-4V uptake was confirmed in excised aortas, colocalized with atherosclerotic plaques delineated by Oil Red O staining and correlated with mRNA levels of VCAM-1 measured by quantitative RT-PCR (R2=0.62, p=0.03). 18F-4V allows noninvasive PET-CT imaging of VCAM-1 in atheromata, has sufficient dynamic range to quantify treatment effects, and correlates with inflammatory gene expression. This approach lends itself to seamless translation to human PET-CT imaging.

scholarly journals Preclinical and Exploratory Clinical Studies of Novel 68Ga-labeled ᴅ-Peptide Antagonist for PET Imaging of TIGIT Expression in Cancers

2021 ◽  
Author(s):  
Xiaobo Wang ◽  
Ming Zhou ◽  
Bei Chen ◽  
Huanhuan Liu ◽  
Jianyang Fang ◽  
...  
Keyword(s):  
Pilot Study ◽  
Pet Imaging ◽  
Ex Vivo ◽  
Ct Imaging ◽  
Whole Body ◽  
Binding Assays ◽  
Pet Ct ◽  
Peptide Antagonist

Abstract Purpose While TIGIT has been propelled under the spotlight as a next-generation target in cancer immunotherapy, anti-TIGIT therapy seems to be promising for a fraction of patients in clinical trials. Therefore, patient stratification is critical for this therapy, which could benefit from a whole-body, non-invasive and quantitative evaluation of TIGIT expression in cancers. In this study, a 68Ga-labeled ᴅ-peptide antagonist, 68Ga-GP12, was developed and validated for PET imaging of TIGIT expression in vitro, in vivo, and first-in-human pilot study. Methods The ᴅ-enantiomer peptide antagonists were modified and radiolabeled with 68Ga. In vitro binding assays were performed in human peripheral blood mononuclear cells (PBMCs) to assess their affinity and specificity. The imaging capacity, biodistribution, pharmacokinetics, and radiation dosimetry were investigated in vivo. Flow cytometry, autoradiography, and immunohistochemical staining were used to confirm the expression of TIGIT ex vivo. The safety and potential of 68Ga-GP12 for PET/CT imaging of TIGIT expression were further evaluated in a first-in-human pilot study with advanced NSCLC. Results 68Ga-labeled ᴅ-peptides were conveniently produced with high radiochemical yields,radiochemical purity and molar activities. In vitro binding assays demonstrated 68Ga-GP12 has favorable affinity and specificity for TIGIT with a KD of 37.28 nM. In vivo and ex vivo studies demonstrated the favorable pharmacokinetics of 68Ga-GP12 for PET imaging of TIGIT expression with high tumor uptake of 4.22 ± 0.68 %ID/g and the tumor-to-muscle ratio of 12.94 ± 2.64 at 60 min post-injection. The primary and metastatic lesions found in the first-in-human studies of 68Ga-GP12 PET/CT imaging were comparable to that in 18F-FDG PET/CT imaging. Moreover, the inhomogenous intra-and-inter-tumoral uptake of 68Ga-GP12 was presented, reflecting the heterogeneity of TIGIT expression levels. Conclusion 68Ga-GP12 is a promising radiotracer for PET imaging of TIGIT expression in cancers, indicating its potential as a potential companion diagnostic for anti-TIGIT therapies.

Abstract 18873: Al 18 F-NOTA-folate Accumulates in Atherosclerotic Plaques and Can be Detected by PET/CT

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Johanna M Silvola ◽  
Xiang-Guo Li ◽  
Jenni Virta ◽  
Guru Prasad Padmasola ◽  
Päivi Marjamäki ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Folate Receptor ◽  
Specific Radioactivity ◽  
Experimental Models ◽  
Atherosclerotic Plaques ◽  
Pet Tracer ◽  
Contrast Enhanced Ct ◽  
Pet Ct ◽  
Atheromatous Plaques

Introduction:Macrophages are a major cell type in inflamed atherosclerotic plaques. Since folate receptor β (FR-β) is highly expressed in activated macrophages, we hypothesized that it might serve as a new marker for inflamed atherosclerotic plaques. Hypothesis: We aimed at evaluating a FR-β targeted PET tracer, Al 18 F NOTA-Folate, for the detection of inflamed atherosclerotic plaques. Methods:Atherosclerotic mice deficient for low density lipoprotein receptor (LDLR -/- ApoB 100/100 , n=12), C57BL control mice (n=9), and Watanabe rabbits (n=4) with endothelial denudation-induced atherosclerosis in the aorta were used. Biodistribution of Al 18 F-NOTA-Folate (specific radioactivity 130 GMq/μmol) was investigated in vivo by PET/contrast enhanced CT and ex vivo by gamma counting and autoradiography of aortic sections. In addition, prior to Al 18 F-NOTA-Folate study, the Watanabe rabbits were PET/CT imaged with 18 F-FDG. Results:Atherosclerotic mice demonstrated large and macrophage-rich atheromatous plaques in the aorta. The in vivo PET/CT revealed significantly higher uptake of Al 18 F-NOTA-Folate in the aortic arch of atherosclerotic mice compared to controls (aorta-to-blood ratio 1.5±0.3 vs. 0.7±0.2, P <0.0001), which were verified by ex vivo measurements. Autoradiography confirmed focally increased uptake of Al 18 F-NOTA-Folate in the atherosclerotic plaques (plaque-to-normal vessel wall ratio 2.6±0.7, P <0.0001). Competitive study with excess of unlabelled folate reduced Al 18 F-NOTA-Folate uptake in the aorta by app. 80% and thus verified the specificity of its binding. In the rabbit aorta, the PET/CT showed a strong focal in vivo uptake of Al 18 F-NOTA-Folate co-localizing with an atherosclerotic abdominal aorta with highest aorta-to-blood ratio of 6.0. For comparison, with 18 F-FDG the ratio was 2.4 in the same area. Conclusions: Al 18 F-NOTA-Folate, targeting FR-β, accumulates in macrophage-rich atherosclerotic plaques, which can be detected in vivo by PET/CT in experimental models of atherosclerosis. Further development of the tracer for imaging of patients with atherosclerosis is warranted.

scholarly journals 18F-ASEM Imaging for Evaluating Atherosclerotic Plaques Linked to α7-Nicotinic Acetylcholine Receptor

2021 ◽  
Vol 9 ◽  
Author(s):  
Tao Yang ◽  
Dawei Wang ◽  
Xiangyi Chen ◽  
Yingkui Liang ◽  
Feng Guo ◽  
...  
Keyword(s):  
Acetylcholine Receptor ◽  
Nicotinic Acetylcholine Receptor ◽  
Abdominal Aorta ◽  
Ct Imaging ◽  
Control Group ◽  
Atherosclerotic Plaques ◽  
Α7 Nicotinic Acetylcholine Receptor ◽  
Nicotinic Acetylcholine ◽  
Pet Ct

BackgroundAtherosclerosis is a chronic vascular inflammatory procedure alongside with lipid efflux disorder and foam cell formation. α7-Nicotinic acetylcholine receptor (α7nAChR) is a gated-calcium transmembrane channel widely expressed in neuron and non-neuron cells, such as monocytes and macrophages, activated T cells, dendritic cells, and mast cells. 18F-ASEM is an inhibitor targeted to α7nAChR that had been successfully applied in nervous system diseases. Previous studies had highlighted that α7nAChR was related to the emergency of vulnerable atherosclerotic plaques with excess inflammation cells. Thus, 18F-ASEM could be a complementary diagnostic approach to atherosclerotic plaques.Materials and MethodsThe synthesis of ASEM precursor and 18F-labeling had been performed successfully. We had established the ApoE–/– mice atherosclerotic plaques model (fed with western diet) and New Zealand rabbits atherosclerotic models (balloon-sprained experiment and western diet). After damage of endothelial cells and primary plaque formation, 18F-ASEM imaging of atherosclerotic plaques linked to α7nAChR had been conducted. In vivo micro-PET/CT imaging of ApoE–/– mice and the control group was performed 1 h after injection of 18F-ASEM (100–150 μCi); PET/CT imaging for rabbits with atherosclerotic plaques and control ones was also performed. Meanwhile, we also conducted CT scan on the abdominal aorta of these rabbits. After that, the animals were sacrificed, and the carotid and abdominal aorta were separately taken out for circular sections. The paraffin-embedded specimens were sectioned with 5 μm thickness and stained with hematoxylin–eosin (H&amp;E) and oil red.ResultsIn vivo vessel binding of 18F-ASEM and α7nAChR expression in the model group with atherosclerosis plaques was significantly higher than that in the control group. PET/CT imaging successfully identified the atherosclerotic plaques in ApoE–/– mice and model rabbits, whereas no obvious signals were detected in normal mice or rabbits. Compared with 18F-FDG, 18F-ASEM had more significant effect on the early monitoring of inflammation in carotid atherosclerotic plaques of ApoE–/– mice and model rabbits. 18F-ASEM had relatively more palpable effect on the imaging of abdominal aorta with atherosclerosis in rabbits. H&amp;E and oil red staining identified the formation of atherosclerotic plaques in model animals, which provided pathological basis for the evaluation of imaging effects.ConclusionWe first confirmed 18F-ASEM as radiotracer with good imaging properties for precise identification of atherosclerotic diseases.

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