Small-animal SPECT/CT imaging of cancer xenografts and pulmonary fibrosis using a 99mTc-labeled integrin αvβ6-targeting cyclic peptide with improved in vivo stability

Photon-counting detector (PCD) can identify absorption features in the multiple ranges of photon energies, which has a great potential in material discrimination. In this paper, we focused on in vivo dual-energy CT imaging to characterize different biomedical compositions. The precision of material decomposition in post-reconstruction space depends on the quality of reconstructed CT images; we used the locally linear embedding (LLE) based online geometric calibration method and GPU-based reconstruction toolbox to reconstruct high-quality CT images. Then, we performed the real experiment and studied materials decomposition with basis material model to discriminate soft tissue and cortical bone of small animal. Finally, the experimental results demonstrated that the proposed method could reconstruct small animal CT images with more slim structures and details, and improve the precision of materials decomposition in dual-energy CT imaging.

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Preclinical Evaluation of [99mTc]Tc-Labeled Anti-EpCAM Nanobody for EpCAM Receptor Expression Imaging By Immuno-SPECT/CT

10.21203/rs.3.rs-951513/v1 ◽

2021 ◽

Author(s):

Tianyu Liu ◽

Yue Wu ◽

Linqing Shi ◽

Liqiang Li ◽

Biao Hu ◽

...

Keyword(s):

Small Animal ◽

Ct Imaging ◽

Receptor Expression ◽

Epcam Expression ◽

Potential Applications ◽

Metastasis Model ◽

Almost All ◽

Ht 29

Abstract Purpose Overexpression of epithelial cell adhesion molecule (EpCAM) plays essential roles in tumorigenesis and tumor progression in almost all epithelium-derived cancer. Monitoring EpCAM expression in tumors can be used for the diagnosis, staging and prognosis of cancer patients, as well as guiding the individualized treatment of EpCAM-targeted drugs. In this study, we described the synthesis and evaluation of a site-specifically [99mTc]Tc-labeled EpCAM-targeted nanobody for the SPECT/CT imaging of EpCAM expression. Methods We first prepared the [99mTc]Tc-HYNIC-G4K, then it was site-specifically connected to EpCAM-targeted nanobody NB4. The in vitro characteristics of [99mTc]Tc-NB4 were investigated in HT-29 (EpCAM-positive) and HL-60 (EpCAM-negative) cells, while the in vivo studies were performed using small-animal SPECT/CT in the subcutaneous tumor models and the lymph node metastasis model to verify the specific targeting capacity as well as the potential applications of [99mTc]Tc-NB4. Results [99mTc]Tc-NB4 displayed a high EpCAM specificity both in vitro and in vivo. SPECT/CT imaging revealed that [99mTc]Tc-NB4 was cleared rapidly from the blood and normal organs except for the kidneys, and HT-29 tumors were clearly visualized in contrast with HL-60 tumors. The uptake value of [99mTc]Tc-NB4 in HT-29 tumors was increased continuously from 3.77 ± 0.39 %ID/g at 0.5 h to 5.53 ± 0.82 %ID/g at 12 h after injection. Moreover, the [99mTc]Tc-NB4 SPECT/CT could clearly image tumor-infiltrating lymph nodes. Conclusion [99mTc]Tc-NB4 is a broad-spectrum, specific and sensitive SPECT radiotracer for the noninvasive imaging of EpCAM expression in the epithelium-derived cancer, and revealed a great potential for the clinical translation.

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In Vivo Respiratory-Gated Micro-CT Imaging in Small-Animal Oncology Models

Molecular Imaging ◽

10.1162/153535004773861723 ◽

2004 ◽

Vol 3 (1) ◽

pp. 55-62 ◽

Cited By ~ 119

Author(s):

Dawn Cavanaugh ◽

Evan Johnson ◽

Roger E. Price ◽

Jonathan Kurie ◽

Elizabeth L. Travis ◽

...

Keyword(s):

Small Animal ◽

Ct Imaging ◽

Micro Ct

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High Throughput PET/CT Imaging Using a Multiple Mouse Imaging System

10.1101/602391 ◽

2019 ◽

Author(s):

Hannah E. Greenwood ◽

Zoltan Nyitrai ◽

Gabor Mocsai ◽

Sandor Hobor ◽

Timothy H. Witney

Keyword(s):

Image Quality ◽

Fdg Pet ◽

Imaging System ◽

Small Animal ◽

Ct Imaging ◽

Small Animal Pet ◽

Pet Ct ◽

Fdg Pet Ct ◽

The Cost

AbstractA considerable limitation of current small animal positron emission tomography/computed tomography (PET/CT) imaging is the low throughput of image acquisitions. Subsequently, to design sufficiently-powered studies, high costs accumulate. Together with Mediso Medical Imaging Systems, a four-bed mouse ‘hotel’ was developed to simultaneously image up to four mice, thereby reducing the cost and maximising radiotracer usage when compared to scans performed with a single mouse bed.MethodsFor physiological evaluation of the four-bed mouse hotel, temperature and anaesthesia were tested for uniformity, followed by [18F]fluorodeoxyglucose (FDG) PET/CT imaging of ‘mini’ image quality (IQ) phantoms specifically designed to fit the new imaging system. Post-reconstruction, National Electrical Manufacturers Association (NEMA) NU-4 tests examined uniformity, recovery coefficients (RCs) and spill-over ratios (SORs). To evaluate the bed under standard in vivo imaging conditions, four mice were simultaneously scanned by dynamic [18F]FDG PET/CT over 60 minutes using the four-bed mouse hotel, with quantified images compared to those acquired using a single mouse bed.ResultsThe bed maintained a constant temperature of 36.8°C ± 0.4°C (n = 4), with anaesthesia distributed evenly to each nose cone (2.9 ± 0.1 L/min, n = 4). The NEMA tests performed on reconstructed mini IQ phantom images acquired using the four-bed mouse hotel revealed values within the tolerable limits for uniformity, RC values in >2mm rods, and SORs in the non-radioactive water- and air-filled chambers. There was low variability in radiotracer uptake in all major organs of mice scanned using the four-animal bed versus those imaged using a single bed imaging platform.ConclusionAnalysis of images acquired using the four-bed mouse hotel confirmed its utility to increase the throughput of small animal PET imaging without considerable loss of image quality and quantitative precision. In comparison to a single mouse bed, the cost and time associated with each scan were substantially reduced.

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In vivo micro-CT imaging of liver lesions in small animal models

Methods ◽

10.1016/j.ymeth.2009.05.016 ◽

2010 ◽

Vol 50 (1) ◽

pp. 20-25 ◽

Cited By ~ 32

Author(s):

Lucia Martiniova ◽

Daniel Schimel ◽

Edwin W. Lai ◽

Andrea Limpuangthip ◽

Richard Kvetnansky ◽

...

Keyword(s):

Animal Models ◽

Small Animal ◽

Ct Imaging ◽

Liver Lesions ◽

Micro Ct ◽

Small Animal Models

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microRNA-186 in extracellular vesicles from bone marrow mesenchymal stem cells alleviates idiopathic pulmonary fibrosis via interaction with SOX4 and DKK1

Stem Cell Research & Therapy ◽

10.1186/s13287-020-02083-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Jing Zhou ◽

Yang Lin ◽

Xiuhua Kang ◽

Zhicheng Liu ◽

Wei Zhang ◽

...

Keyword(s):

Bone Marrow ◽

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Extracellular Vesicles ◽

Luciferase Assay ◽

Therapeutic Effects ◽

Loss Of Function ◽

Fibroblast Activation ◽

Promising Therapeutic Approach

Abstract Background Previous reports have identified that human bone marrow mesenchymal stem cell-derived extracellular vesicles (BMSC-EVs) with their cargo microRNAs (miRNAs) are a promising therapeutic approach for the treatment of idiopathic pulmonary fibrosis (IPF). Therefore, we explored whether delivery of microRNA-186 (miR-186), a downregulated miRNA in IPF, by BMSC EVs could interfere with the progression of IPF in a murine model. Methods In a co-culture system, we assessed whether BMSC-EVs modulated the activation of fibroblasts. We established a mouse model of PF to evaluate the in vivo therapeutic effects of BMSC-EVs and determined miR-186 expression in BMSC-EVs by polymerase chain reaction. Using a loss-of-function approach, we examined how miR-186 delivered by BMSC-EVs affected fibroblasts. The putative relationship between miR-186 and SRY-related HMG box transcription factor 4 (SOX4) was tested using luciferase assay. Next, we investigated whether EV-miR-186 affected fibroblast activation and PF by targeting SOX4 and its downstream gene, Dickkopf-1 (DKK1). Results BMSC-EVs suppressed lung fibroblast activation and delayed IPF progression in mice. miR-186 was downregulated in IPF but enriched in the BMSC-EVs. miR-186 delivered by BMSC-EVs could suppress fibroblast activation. Furthermore, miR-186 reduced the expression of SOX4, a target gene of miR-186, and hence suppressed the expression of DKK1. Finally, EV-delivered miR-186 impaired fibroblast activation and alleviated PF via downregulation of SOX4 and DKK1. Conclusion In conclusion, miR-186 delivered by BMSC-EVs suppressed SOX4 and DKK1 expression, thereby blocking fibroblast activation and ameliorating IPF, thus presenting a novel therapeutic target for IPF.

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Regorafenib-Attenuated, Bleomycin-Induced Pulmonary Fibrosis by Inhibiting the TGF-β1 Signaling Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms22041985 ◽

2021 ◽

Vol 22 (4) ◽

pp. 1985

Author(s):

Xiaohe Li ◽

Ling Ma ◽

Kai Huang ◽

Yuli Wei ◽

Shida Long ◽

...

Keyword(s):

Pulmonary Fibrosis ◽

Signaling Pathway ◽

Transforming Growth Factor ◽

Kinase Inhibitor ◽

In Vivo Experiments ◽

Age Related ◽

And Migration ◽

Tgf Β1

Idiopathic pulmonary fibrosis (IPF) is a fatal and age-related pulmonary disease. Nintedanib is a receptor tyrosine kinase inhibitor, and one of the only two listed drugs against IPF. Regorafenib is a novel, orally active, multi-kinase inhibitor that has similar targets to nintedanib and is applied to treat colorectal cancer and gastrointestinal stromal tumors in patients. In this study, we first identified that regorafenib could alleviate bleomycin-induced pulmonary fibrosis in mice. The in vivo experiments indicated that regorafenib suppresses collagen accumulation and myofibroblast activation. Further in vitro mechanism studies showed that regorafenib inhibits the activation and migration of myofibroblasts and extracellular matrix production, mainly through suppressing the transforming growth factor (TGF)-β1/Smad and non-Smad signaling pathways. In vitro studies have also indicated that regorafenib could augment autophagy in myofibroblasts by suppressing TGF-β1/mTOR (mechanistic target of rapamycin) signaling, and could promote apoptosis in myofibroblasts. In conclusion, regorafenib attenuates bleomycin-induced pulmonary fibrosis by suppressing the TGF-β1 signaling pathway.

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Role of interleukins in the pathogenesis of pulmonary fibrosis

Cell Death Discovery ◽

10.1038/s41420-021-00437-9 ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Yi Xin She ◽

Qing Yang Yu ◽

Xiao Xiao Tang

Keyword(s):

Pulmonary Fibrosis ◽

Therapeutic Strategy ◽

Future Directions ◽

Regulation Mechanisms ◽

Underlying Mechanisms ◽

Multiple Cells ◽

The Relationship

AbstractInterleukins, a group of cytokines participating in inflammation and immune response, are proved to be involved in the formation and development of pulmonary fibrosis. In this article, we reviewed the relationship between interleukins and pulmonary fibrosis from the clinical, animal, as well as cellular levels, and discussed the underlying mechanisms in vivo and in vitro. Despite the effects of interleukin-targeted treatment on experimental pulmonary fibrosis, clinical applications are lacking and unsatisfactory. We conclude that intervening in one type of interleukins with similar functions in IPF may not be enough to stop the development of fibrosis as it involves a complex network of regulation mechanisms. Intervening interleukins combined with other existing therapy or targeting interleukins affecting multiple cells/with different functions at the same time may be one of the future directions. Furthermore, the intervention time is critical as some interleukins play different roles at different stages. Further elucidation on these aspects would provide new perspectives on both the pathogenesis mechanism, as well as the therapeutic strategy and drug development.

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