In vivo MRI detection of atherosclerosis in ApoE-deficient mice by using tenascin-C-targeted USPIO

2018 ◽  
Vol 59 (12) ◽  
pp. 1431-1437 ◽  
Author(s):  
Yan Li ◽  
Jun Liu ◽  
Jun-wen Huang ◽  
Jia-cheng Song ◽  
Zhan-long Ma ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Cerebrovascular Diseases ◽  
Control Group ◽  
Atherosclerotic Plaques ◽  
Relative Signal Intensity ◽  
Tenascin C ◽  
Imaging Tool ◽  
Life Threatening ◽  
Magnetic Resonance Imaging Mri

Background Atherosclerosis is the main cause of cardiovascular and cerebrovascular diseases. Non-invasive molecular imaging to detect and characterize the plaques is essential for reducing life-threatening cardiovascular events. Purpose To investigate the possibility of the anti-tenascin-C-USPIO specific probe as a molecular marker of atherosclerotic plaques detected by 7.0-T magnetic resonance imaging (MRI). Material and Methods Twenty ApoE-/- mice fed with a high fat diet were used for detecting the aorta arch atherosclerotic plaques by 7.0-T MRI at 16 and 24 weeks. Ten mice in the targeted group were injected with anti-tenascin-C-USPIO and another ten in the control group were injected with pure USPIO (n = 5 each time point in each group). Histopathologic examination was used to evaluate the plaques and immunohistochemistry analysis was used to compare tenascin-C expression. Results The relative signal intensity (rSI) changes of the targeted group decreased more than those of the control group (16 weeks: −15.65 ± 0.78% vs. −3.43 ± 2.57%; 24 weeks: −26.38 ± 1.54% vs. −11.12 ± 1.60%, respectively; P < 0.05). Histopathological analyses demonstrated visible atherosclerotic plaques formation and development over time from 16 weeks to 24 weeks. Tenascin-C expression of the plaques at 24 weeks was higher than that at 16 weeks (0.22 ± 0.04 vs. 0.13 ± 0.02, P < 0.05). The MR images correlated well with the progression of atherosclerotic plaques. Conclusion Tenascin-C expression increased with the progression of atherosclerosis. Anti-tenascin-C-USPIO could provide a useful molecular imaging tool for detecting and monitoring atherosclerotic plaques by MRI.

scholarly journals Preclinical Evaluation of [18F]FACH in Healthy Mice and Piglets: An 18F-Labeled Ligand for Imaging of Monocarboxylate Transporters with PET

2021 ◽  
Vol 22 (4) ◽  
pp. 1645
Author(s):  
Daniel Gündel ◽  
Masoud Sadeghzadeh ◽  
Winnie Deuther-Conrad ◽  
Barbara Wenzel ◽  
Paul Cumming ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Ex Vivo ◽  
Specific Binding ◽  
Monocarboxylate Transporters ◽  
Binding Potential ◽  
Kidney Cortex ◽  
Binding Studies ◽  
Imaging Tool ◽  
Pre Treatment

The expression of monocarboxylate transporters (MCTs) is linked to pathophysiological changes in diseases, including cancer, such that MCTs could potentially serve as diagnostic markers or therapeutic targets. We recently developed [18F]FACH as a radiotracer for non-invasive molecular imaging of MCTs by positron emission tomography (PET). The aim of this study was to evaluate further the specificity, metabolic stability, and pharmacokinetics of [18F]FACH in healthy mice and piglets. We measured the [18F]FACH plasma protein binding fractions in mice and piglets and the specific binding in cryosections of murine kidney and lung. The biodistribution of [18F]FACH was evaluated by tissue sampling ex vivo and by dynamic PET/MRI in vivo, with and without pre-treatment by the MCT inhibitor α-CCA-Na or the reference compound, FACH-Na. Additionally, we performed compartmental modelling of the PET signal in kidney cortex and liver. Saturation binding studies in kidney cortex cryosections indicated a KD of 118 ± 12 nM and Bmax of 6.0 pmol/mg wet weight. The specificity of [18F]FACH uptake in the kidney cortex was confirmed in vivo by reductions in AUC0–60min after pre-treatment with α-CCA-Na in mice (−47%) and in piglets (−66%). [18F]FACH was metabolically stable in mouse, but polar radio-metabolites were present in plasma and tissues of piglets. The [18F]FACH binding potential (BPND) in the kidney cortex was approximately 1.3 in mice. The MCT1 specificity of [18F]FACH uptake was confirmed by displacement studies in 4T1 cells. [18F]FACH has suitable properties for the detection of the MCTs in kidney, and thus has potential as a molecular imaging tool for MCT-related pathologies, which should next be assessed in relevant disease models.

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 Near-Infrared Molecular Imaging of Glioblastoma by Miltuximab®-IRDye800CW as a Potential Tool for Fluorescence-Guided Surgery

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 984 ◽  
Author(s):  
Dmitry M. Polikarpov ◽  
Douglas H. Campbell ◽  
Lucinda S. McRobb ◽  
Jiehua Wu ◽  
Maria E. Lund ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Near Infrared ◽  
Ex Vivo ◽  
Extent Of Resection ◽  
Fluorescent Imaging ◽  
Control Group ◽  
Guided Surgery ◽  
Fluorescence Guided Surgery ◽  
Specific Accumulation

Glioblastoma (GBM) is one of the most aggressive tumors and its 5-year survival is approximately 5%. Fluorescence-guided surgery (FGS) improves the extent of resection and leads to better prognosis. Molecular near-infrared (NIR) imaging appears to outperform conventional FGS, however, novel molecular targets need to be identified in GBM. Proteoglycan glypican-1 (GPC-1) is believed to be such a target as it is highly expressed in GBM and is associated with poor prognosis. We hypothesize that an anti-GPC-1 antibody, Miltuximab®, conjugated with the NIR dye, IRDye800CW (IR800), can specifically accumulate in a GBM xenograft and provide high-contrast in vivo fluorescent imaging in rodents following systemic administration. Miltuximab® was conjugated with IR800 and intravenously administered to BALB/c nude mice bearing a subcutaneous U-87 GBM hind leg xenograft. Specific accumulation of Miltuximab®-IR800 in subcutaneous xenograft tumor was detected 24 h later using an in vivo fluorescence imager. The conjugate did not cause any adverse events in mice and caused strong fluorescence of the tumor with tumor-to-background ratio (TBR) reaching 10.1 ± 2.8. The average TBR over the 10-day period was 5.8 ± 0.6 in mice injected with Miltuximab®-IR800 versus 2.4 ± 0.1 for the control group injected with IgG-IR800 (p = 0.001). Ex vivo assessment of Miltuximab®-IR800 biodistribution confirmed its highly specific accumulation in the tumor. The results of this study confirm that Miltuximab®-IR800 holds promise for intraoperative fluorescence molecular imaging of GBM and warrants further studies.

scholarly journals PDTM-04. EARLY DETECTION BY MRI OF MOUSE MODELS WITH DIFFUSE INTRINSIC PONTINE GLIOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi187-vi187
Author(s):  
Lincy Thomas ◽  
Rheal Towner ◽  
Rafal Gulej ◽  
Nataliya Smith ◽  
Michelle Zalles ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Mouse Models ◽  
Treatment Options ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Control Group ◽  
Pontine Glioma ◽  
Dismal Prognosis ◽  
Magnetic Resonance Imaging Mri ◽  
Tumor In Childhood

Abstract Diffuse intrinsic pontine glioma (DIPG) is the most common brainstem tumor in childhood with a very devastating prognosis and no curative treatment options as of yet. Approximately 300 children in the U.S. are diagnosed with DIPG each year. Our project hopes to assess the effectiveness of OKlahoma Nitrone-007 (OKN-007) as a therapeutic agent for DIPG. This agent has shown promise in prior studies involving pediatric glioma mouse models by decreasing growth of blood vessels, which is essential for any tumor progression, and by decreasing temozolomide (TMZ) resistance when used as adjunct therapy in adult GBM. We have successfully created an in vivo DIPG model using post-mortem patient-derived neurospheres, harboring the H3 K27M mutation, injected into the pontine region of immunocompromised mouse (SCID) brainstems via a stereotaxic device. After surgical implantation, mice are imaged every week using a 7.0 Tesla 30-cm bore Bruker Biospec Magnetic Resonance Imaging (MRI) system to assess tumor growth and progression of disease. We describe to you the first pre-clinical DIPG mouse model that shows evidence of tumor growth as early as 42 days, as detected on T2-weighted MR images. Another characteristic feature is that the blood-brain barrier (BBB) is intact in this DIPG model, as assessed by contrast-enhanced MRI. Additional MRI methods, including diffusion-weighted imaging (DWI), and perfusion imaging (arterial spin labeling) are also evaluated. Prior pre-clinical DIPG mouse models only had tumor detection by MRI 78 days after implantation. Once the tumors are large enough for treatment (clinically relevant), we separate the mice into a control group (no treatment), OKN-007 treatment alone, as well as combination therapy with OKN-007 and TMZ. With the dismal prognosis and limited effective chemotherapy available for DIPG, there is significant room for continued research studies to help clinicians better understand and treat pediatric DIPG patients.

scholarly journals Imaging Collagen in Intact Viable Healthy and Atherosclerotic Arteries Using Fluorescently Labeled CNA35 and Two-Photon Laser Scanning Microscopy

2007 ◽  
Vol 6 (4) ◽  
pp. 7290.2007.00021 ◽  
Author(s):  
Remco T.A. Megens ◽  
Mirjam G.A. oude Egbrink ◽  
Jack P.M. Cleutjens ◽  
Marijke J.E. Kuijpers ◽  
Paul H.M. Schiffers ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Apolipoprotein E ◽  
Carotid Arteries ◽  
Ex Vivo ◽  
Atherosclerotic Plaques ◽  
Type I ◽  
Two Photon ◽  
Tunica Adventitia ◽  
Molecular Imaging Agent

We evaluated CNA35 as a collagen marker in healthy and atherosclerotic arteries of mice after both ex vivo and in vivo administration and as a molecular imaging agent for the detection of atherosclerosis. CNA35 conjugated with fluorescent Oregon Green 488 (CNA35/OG488) was administered ex vivo to mounted viable muscular (uterine), elastic (carotid), and atherosclerotic (carotid) arteries and fresh arterial rings. Two-photon microscopy was used for imaging. CNA35/OG488 labeling in healthy elastic arteries was compared with collagen type I, III, and IV antibody labeling in histologic sections. For in vivo labeling experiments, CNA35/OG488 was injected intravenously in C57BL6/J and apolipoprotein E−/− mice. Ex vivo CNA35/OG488 strongly labeled collagen in the tunica adventitia, media, and intima of muscular arteries. In healthy elastic arteries, tunica adventitia was strongly labeled, but labeling in tunica media and intima was prevented by endothelium and elastic laminae. Histology confirmed the affinity of CNA35 for type I, III, and IV collagen in arteries. Strong CNA35/OG488 labeling was found in atherosclerotic plaques. In vivo applied CNA35/OG488 minimally labeled the tunica intima of healthy carotid arteries. Atherosclerotic plaques in apolipoprotein E−/− mice exhibited large uptake. CNA35/OG488 imaging in organs revealed endothelium as a limiting barrier for in vivo uptake. CNA35/OG488 is a good molecular imaging agent for atherosclerosis.

scholarly journals Multimodality Molecular Imaging of Stem Cells Therapy for Stroke

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Fangfang Chao ◽  
Yehua Shen ◽  
Hong Zhang ◽  
Mei Tian
Keyword(s):  
Stem Cells ◽  
Molecular Imaging ◽  
Multimodality Imaging ◽  
Imaging Techniques ◽  
Potential Method ◽  
Nuclear Medicine Imaging ◽  
Therapeutic Benefits ◽  
Stem Cells Therapy ◽  
Magnetic Resonance Imaging Mri

Stem cells have been proposed as a promising therapy for treating stroke. While several studies have demonstrated the therapeutic benefits of stem cells, the exact mechanism remains elusive. Molecular imaging provides the possibility of the visual representation of biological processes at the cellular and molecular level. In order to facilitate research efforts to understand the stem cells therapeutic mechanisms, we need to further develop means of monitoring these cells noninvasively, longitudinally and repeatedly. Because of tissue depth and the blood-brain barrier (BBB), in vivo imaging of stem cells therapy for stroke has unique challenges. In this review, we describe existing methods of tracking transplanted stem cells in vivo, including magnetic resonance imaging (MRI), nuclear medicine imaging, and optical imaging (OI). Each of the imaging techniques has advantages and drawbacks. Finally, we describe multimodality imaging strategies as a more comprehensive and potential method to monitor transplanted stem cells for stroke.

Molecular Imaging of Vulnerable Atherosclerotic Plaques in Vivo with Osteopontin-Specific Upconversion Nanoprobes

ACS Nano ◽  
2017 ◽  
Vol 11 (2) ◽  
pp. 1816-1825 ◽  
Author(s):  
Ruirui Qiao ◽  
Hongyu Qiao ◽  
Yan Zhang ◽  
Yabin Wang ◽  
Chongwei Chi ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Atherosclerotic Plaques

scholarly journals Histotripsy Clot Liquefaction in a Porcine Intracerebral Hemorrhage Model

Neurosurgery ◽  
2019 ◽  
Vol 86 (3) ◽  
pp. 429-436 ◽  
Author(s):  
Tyler Gerhardson ◽  
Jonathan R Sukovich ◽  
Neeraj Chaudhary ◽  
Thomas L Chenevert ◽  
Kim Ives ◽  
...  
Keyword(s):  
Intracerebral Hemorrhage ◽  
Focused Ultrasound ◽  
Neurological Dysfunction ◽  
Control Group ◽  
Average Volume ◽  
Ultrasound Technique ◽  
Significant Disability ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain

Abstract BACKGROUND Intracerebral hemorrhage (ICH) is characterized by a 30-d mortality rate of 40% and significant disability for those who survive. OBJECTIVE To investigate the initial safety concerns of histotripsy mediated clot liquefaction and aspiration in a porcine ICH model. Histotripsy is a noninvasive, focused ultrasound technique that generates cavitation to mechanically fractionate tissue. Histotripsy has the potential to liquefy clot in the brain and facilitate minimally invasive aspiration. METHODS About 1.75-mL clots were formed in the frontal lobe of the brain (n = 18; n = 6/group). The centers of the clots were liquefied with histotripsy 48 h after formation, and the content was either evacuated or left within the brain. A control group was left untreated. Pigs underwent magnetic resonance imaging (MRI) 7 to 8 d after clot formation and were subsequently euthanized. Neurological behavior was assessed throughout. Histological analysis was performed on harvested brains. A subset of pigs underwent acute analysis (≤6 h). RESULTS Histotripsy was able to liquefy the center of clots without direct damage to the perihematomal brain tissue. An average volume of 0.9 ± 0.5 mL was drained after histotripsy treatment. All groups showed mild ischemia and gliosis in the perihematomal region; however, there were no deaths or signs of neurological dysfunction in any groups. CONCLUSION This study presents the first analysis of histotripsy-based liquefaction of ICH in vivo. Histotripsy safely liquefies clots without significant additional damage to the perihematomal region. The liquefied content of the clot can be easily evacuated, and the undrained clot has no effect on pig survival or neurological behavior.

scholarly journals Molecular Imaging of Inflammatory Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 152
Author(s):  
Meredith A. Jones ◽  
William M. MacCuaig ◽  
Alex N. Frickenstein ◽  
Seda Camalan ◽  
Metin N. Gurcan ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Contrast Agents ◽  
Inflammatory Diseases ◽  
Chronic Obstructive ◽  
Preclinical Research ◽  
Irreversible Damage ◽  
Obstructive Pulmonary Disease ◽  
Inflammatory State ◽  
Magnetic Resonance Imaging Mri

Inflammatory diseases include a wide variety of highly prevalent conditions with high mortality rates in severe cases ranging from cardiovascular disease, to rheumatoid arthritis, to chronic obstructive pulmonary disease, to graft vs. host disease, to a number of gastrointestinal disorders. Many diseases that are not considered inflammatory per se are associated with varying levels of inflammation. Imaging of the immune system and inflammatory response is of interest as it can give insight into disease progression and severity. Clinical imaging technologies such as computed tomography (CT) and magnetic resonance imaging (MRI) are traditionally limited to the visualization of anatomical information; then, the presence or absence of an inflammatory state must be inferred from the structural abnormalities. Improvement in available contrast agents has made it possible to obtain functional information as well as anatomical. In vivo imaging of inflammation ultimately facilitates an improved accuracy of diagnostics and monitoring of patients to allow for better patient care. Highly specific molecular imaging of inflammatory biomarkers allows for earlier diagnosis to prevent irreversible damage. Advancements in imaging instruments, targeted tracers, and contrast agents represent a rapidly growing area of preclinical research with the hopes of quick translation to the clinic.

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