In vivo molecular imaging of myocardial angiogenesis using the αvβ3 integrin-targeted tracer 99mTc-RAFT-RGD

Abstract Background Schwann cells (SCs) play a crucial role in the repair of peripheral nerves. This is due to their ability to proliferate, migrate, and provide trophic support to axon regrowth. During peripheral nerve injury, SCs de-differentiate and reprogram to gain the ability to repair nerves. Cysteine-rich 61 (Cyr61/CCN1) is a member of the CCN family of matrix cell proteins and have been reported to be abundant in the secretome of repair mediating SCs. In this study we investigate the function of Cyr61 in SCs. Results We observed Cyr61 was expressed both in vivo and in vitro. The promoting effect of Cyr61 on SC proliferation and migration was through autocrine and paracrine mechanisms. SCs expressed αvβ3 integrin and the effect of Cyr61 on SC proliferation and migration could be blocked via αvβ3 integrin. Cyr61 could influence c-Jun protein expression in cultured SCs. Conclusions In this study, we found that Cyr61 promotes SC proliferation and migration via αvβ3 integrin and regulates c-Jun expression. Our study contributes to the understanding of cellular and molecular mechanisms underlying SC’s function during nerve injury, and thus, may facilitate the regeneration of peripheral nerves after injury.

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Targeting the Extracellular Matrix in Abdominal Aortic Aneurysms Using Molecular Imaging Insights

International Journal of Molecular Sciences ◽

10.3390/ijms22052685 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2685

Author(s):

Lisa Adams ◽

Julia Brangsch ◽

Bernd Hamm ◽

Marcus R. Makowski ◽

Sarah Keller

Keyword(s):

Extracellular Matrix ◽

Molecular Imaging ◽

Molecular Targets ◽

Abdominal Aortic Aneurysms ◽

Aortic Aneurysms ◽

Type I ◽

Target Tissue ◽

Pharmacologic Treatment ◽

Abdominal Aortic

This review outlines recent preclinical and clinical advances in molecular imaging of abdominal aortic aneurysms (AAA) with a focus on molecular magnetic resonance imaging (MRI) of the extracellular matrix (ECM). In addition, developments in pharmacologic treatment of AAA targeting the ECM will be discussed and results from animal studies will be contrasted with clinical trials. Abdominal aortic aneurysm (AAA) is an often fatal disease without non-invasive pharmacologic treatment options. The ECM, with collagen type I and elastin as major components, is the key structural component of the aortic wall and is recognized as a target tissue for both initiation and the progression of AAA. Molecular imaging allows in vivo measurement and characterization of biological processes at the cellular and molecular level and sets forth to visualize molecular abnormalities at an early stage of disease, facilitating novel diagnostic and therapeutic pathways. By providing surrogate criteria for the in vivo evaluation of the effects of pharmacological therapies, molecular imaging techniques targeting the ECM can facilitate pharmacological drug development. In addition, molecular targets can also be used in theranostic approaches that have the potential for timely diagnosis and concurrent medical therapy. Recent successes in preclinical studies suggest future opportunities for clinical translation. However, further clinical studies are needed to validate the most promising molecular targets for human application.

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Multi-Modal Multi-Spectral Intravital Microscopic Imaging of Signaling Dynamics in Real-Time during Tumor–Immune Interactions

Cells ◽

10.3390/cells10030499 ◽

2021 ◽

Vol 10 (3) ◽

pp. 499

Author(s):

Tracy W. Liu ◽

Seth T. Gammon ◽

David Piwnica-Worms

Keyword(s):

Molecular Imaging ◽

Single Cell ◽

Real Time ◽

Bioluminescence Imaging ◽

Emission Spectra ◽

Ccd Camera ◽

Microscopic Imaging ◽

Signaling Dynamics ◽

Window Chamber

Intravital microscopic imaging (IVM) allows for the study of interactions between immune cells and tumor cells in a dynamic, physiologically relevant system in vivo. Current IVM strategies primarily use fluorescence imaging; however, with the advances in bioluminescence imaging and the development of new bioluminescent reporters with expanded emission spectra, the applications for bioluminescence are extending to single cell imaging. Herein, we describe a molecular imaging window chamber platform that uniquely combines both bioluminescent and fluorescent genetically encoded reporters, as well as exogenous reporters, providing a powerful multi-plex strategy to study molecular and cellular processes in real-time in intact living systems at single cell resolution all in one system. We demonstrate that our molecular imaging window chamber platform is capable of imaging signaling dynamics in real-time at cellular resolution during tumor progression. Importantly, we expand the utility of IVM by modifying an off-the-shelf commercial system with the addition of bioluminescence imaging achieved by the addition of a CCD camera and demonstrate high quality imaging within the reaches of any biology laboratory.

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

International Journal of Molecular Sciences ◽

10.3390/ijms22041645 ◽

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.

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