Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 12

Imaging Related Abstracts

12 Design and Preliminary Evaluation of Benzoxazolone-Based Agents for Targeting Mitochondrial-Located Translocator Protein

Authors: Nidhi Chadha, A. K. Tiwari, Marilyn D. Milton, Anil K. Mishra


Translocator protein (18 kDa) TSPO is highly expressed during microglia activation in neuroinflammation. Although a number of PET ligands have been developed for the visualization of activated microglia, one of the advantageous approaches is to develop potential optical imaging (OI) probe. Our study involves computational screening, synthesis and evaluation of TSPO ligand through various imaging modalities namely PET/SPECT/Optical. The initial computational screening involves pharmacophore modeling from the library designing having oxo-benzooxazol-3-yl-N-phenyl-acetamide groups and synthesis for visualization of efficacy of these compounds as multimodal imaging probes. Structure modeling of monomer, Ala147Thr mutated, parallel and anti-parallel TSPO dimers was performed and docking analysis was performed for distinct binding sites. Computational analysis showed pattern of variable binding profile of known diagnostic ligands and NBMP via interactions with conserved residues along with TSPO’s natural polymorphism of Ala147→Thr, which showed alteration in the binding affinity due to considerable changes in tertiary structure. Preliminary in vitro binding studies shows binding affinity in the range of 1-5 nm and selectivity was also certified by blocking studies. In summary, this skeleton was found to be potential probe for TSPO imaging due to ease in synthesis, appropriate lipophilicity and reach to specific region of brain.

Keywords: Imaging, Molecular Modeling, docking, TSPO

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11 Evaluation of the Radiolabelled 68GA-DOTATOC Complex in Adenocarcinoma Breast Cancer

Authors: H. Yousefnia, S. Zolghadri, A. R. Jalilian, M. Naderi, A. Ramazani, B. Alirzapour


Nowadays, 68Ga-DOTATOC has been known as a potential agent for the detection of neuroendocrine tumours and it has indicated higher sensitivity compared with the 111In-Octeroetide. The aim of this study was to evaluate the effectiveness of this new agent in the diagnosis of adenocarcinoma breast cancer. 68Ga-DOTATOC was prepared with the radiochemical purity of higher than 98% and by the specific activity of 39.6 TBq/mmol. 37 MBq of the complex was injected intravenously into the BULB/c mice with adenocarcinoma breast cancer. PET/CT images were acquired after 30, 60 and 90 min post injection demonstrated significant accumulation in the tumour sites. Also, considerable activity was observed in the kidney and bladder as the main routs of excretion. Generally, the results showed that 68Ga-DOTATOC can be considered as a suitable complex for diagnosis of the adenocarcinoma breast cancer using PET procedure.

Keywords: Imaging, octreotide, adenocarcinoma breast cancer

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10 Preparation and Quality Control of 68Ga-1,2-Propylene Di-Amino Tetra (Methylenephosphonic Acid)

Authors: H. Yousefnia, S. Zolghadri, A. R. Jalilian, A. Ramazani, N. Tadayon


Bone metastases occur in many patients with solid malignant tumors. Recently, 1,2 propylene di-amino tetra methylenephosphonic acid (PDTMP) has been introduced as a suitable carrier in the development of therapeutic bone-avid radiopharmaceuticals. In this study, due to the desirable characteristics of 68Ga, 68Ga-PDTMP was prepared. 68Ga was obtained from SnO2 based generator. A stock solution of PDTMP was prepared by dissolving in 2 N NaOH. A certain volume of the stock solution was added to the vial containing 68GaCl3 and the pH of the mixture was adjusted to 4 using HEPES. Radiochemical purity of the radiolabelled complex was checked by thin layer chromatography. 68Ga-PDTMP was prepared in only 15 min with radiochemical purity of more than 98%. This new bone-seeking complex can be considered as a good candidate of PET-based radiopharmaceutical for imaging of bone metastases.

Keywords: Imaging, PDTMP, bone metastases, Ga-68

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9 Biodistribution Study of 68GA-PDTMP as a New Bone Pet Imaging Agent

Authors: H. Yousefnia, S. Zolghadri, A. R. Jalilian, A. Ramazani, N. Tadayon


In this study, 68Ga-PDTMP was prepared as a new agent for bone imaging. 68Ga was obtained from SnO2 based generator. A certain volume of the PDTMP solution was added to the vial containing 68GaCl3 and the pH of the mixture was adjusted to 4 using HEPES. Radiochemical purity of the radiolabelled complex was checked by thin layer chromatography. Biodistribution of this new agent was assessed in rats after intravenously injection of the complex. For this purpose, the rats were killed at specified times after injection and the weight and activity of each organ was measured. Injected dose per gram was calculated by dividing the activity of each organ to the total injected activity and the mass of each organ. As expected the most of the activity was accumulated in the bone tissue. The radiolabelled compound was extracted from blood very fast. This new bone-seeking complex can be considered as a good candidate of PET-based radiopharmaceutical for imaging of bone metastases.

Keywords: Imaging, biodistribution, PDTMP, Ga-68

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8 Application of MRI in Radioembolization Imaging and Dosimetry

Authors: Salehi Zahabi Saleh, Rajabi Hosaien, Rasaneh Samira


Yttrium-90 (90Y) radioembolisation(RE) is increasingly used for the treatment of patients with unresectable primary or metastatic liver tumours. Image-based approaches to assess microsphere distribution after RE have gained interest but are mostly hampered by the limited imaging possibilities of the Isotope 90Y. Quantitative 90Y-SPECT imaging has limited spatial resolution because it is based on 90Y Bremsstrahlung whereas 90Y-PET has better spatial resolution but low sensitivity. As a consequence, new alternative methods of visualizing the microspheres have been investigated, such as MR imaging of iron-labelled microspheres. It was also shown that MRI combines high sensitivity with high spatial and temporal resolution and with superior soft tissue contrast and thus can be used to cover a broad range of clinically interesting imaging parameters.The aim of the study in this article was to investigate the capability of MRI to measure the intrahepatic microsphere distribution in order to quantify the absorbed radiation dose in RE.

Keywords: Dosimetry, Imaging, MRI, radioembolisation

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7 Enhancing of Laser Imaging by Using Ultrasound Effect

Authors: Hayder Raad Hafuze, Munqith Saleem Dawood, Jamal Abdul Jabbar


The effect of using both ultrasounds with laser in medical imaging of the biological tissue has been studied in this paper. Different wave lengths of incident laser light (405 nm, 532 nm, 650 nm, 808 nm and 1064 nm) were used with different ultrasound frequencies (1MHz and 3.3MHz). The results showed that, the change of acoustic intensity enhance the laser penetration of the tissue for different thickness. The existence of the ideal Raman-Nath diffraction pattern were investigated in terms of phase delay and incident angle.

Keywords: laser, Imaging, tissue, Ultrasound, effect

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6 Foslip Loaded and CEA-Affimer Functionalised Silica Nanoparticles for Fluorescent Imaging of Colorectal Cancer Cells

Authors: Thomas Hughes, Paul Millner, Yazan S. Khaled, Shazana Shamsuddin, Jim Tiernan, Mike McPherson, David G. Jayne


Introduction: There is a need for real-time imaging of colorectal cancer (CRC) to allow tailored surgery to the disease stage. Fluorescence guided laparoscopic imaging of primary colorectal cancer and the draining lymphatics would potentially bring stratified surgery into clinical practice and realign future CRC management to the needs of patients. Fluorescent nanoparticles can offer many advantages in terms of intra-operative imaging and therapy (theranostic) in comparison with traditional soluble reagents. Nanoparticles can be functionalised with diverse reagents and then targeted to the correct tissue using an antibody or Affimer (artificial binding protein). We aimed to develop and test fluorescent silica nanoparticles and targeted against CRC using an anti-carcinoembryonic antigen (CEA) Affimer (Aff). Methods: Anti-CEA and control Myoglobin Affimer binders were subcloned into the expressing vector pET11 followed by transformation into BL21 Star™ (DE3) E.coli. The expression of Affimer binders was induced using 0.1 mM isopropyl β-D-1-thiogalactopyranoside (IPTG). Cells were harvested, lysed and purified using nickle chelating affinity chromatography. The photosensitiser Foslip (soluble analogue of 5,10,15,20-Tetra(m-hydroxyphenyl) chlorin) was incorporated into the core of silica nanoparticles using water-in-oil microemulsion technique. Anti-CEA or control Affs were conjugated to silica nanoparticles surface using sulfosuccinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (sulfo SMCC) chemical linker. Binding of CEA-Aff or control nanoparticles to colorectal cancer cells (LoVo, LS174T and HC116) was quantified in vitro using confocal microscopy. Results: The molecular weights of the obtained band of Affimers were ~12.5KDa while the diameter of functionalised silica nanoparticles was ~80nm. CEA-Affimer targeted nanoparticles demonstrated 9.4, 5.8 and 2.5 fold greater fluorescence than control in, LoVo, LS174T and HCT116 cells respectively (p < 0.002) for the single slice analysis. A similar pattern of successful CEA-targeted fluorescence was observed in the maximum image projection analysis, with CEA-targeted nanoparticles demonstrating 4.1, 2.9 and 2.4 fold greater fluorescence than control particles in LoVo, LS174T, and HCT116 cells respectively (p < 0.0002). There was no significant difference in fluorescence for CEA-Affimer vs. CEA-Antibody targeted nanoparticles. Conclusion: We are the first to demonstrate that Foslip-doped silica nanoparticles conjugated to anti-CEA Affimers via SMCC allowed tumour cell-specific fluorescent targeting in vitro, and had shown sufficient promise to justify testing in an animal model of colorectal cancer. CEA-Affimer appears to be a suitable targeting molecule to replace CEA-Antibody. Targeted silica nanoparticles loaded with Foslip photosensitiser is now being optimised to drive photodynamic killing, via reactive oxygen generation.

Keywords: Imaging, Antibodies, colorectal cancer, silica nanoparticles, Affimers

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5 Automatic Vehicle Detection Using Circular Synthetic Aperture Radar Image

Authors: Leping Chen, Daoxiang An, Xiaotao Huang


Automatic vehicle detection using synthetic aperture radar (SAR) image has been widely researched, as well as using optical remote sensing images. However, most researches treat the detection as an independent problem, failing to make full use of SAR data information. In circular SAR (CSAR), the two long borders of vehicle will shrink if the imaging surface is set higher than the reference one. Based on above variance, an automatic vehicle detection using CSAR image is proposed to enhance detection ability under complex environment, such as vehicles’ closely packing, which confuses the detector. The detection method uses the multiple images generated by different height plane to obtain an energy-concentrated image for detecting and then uses the maximally stable extremal regions method (MSER) to detect vehicles. A result of vehicles’ detection is given to verify the effectiveness and correctness of proposed method.

Keywords: Imaging, Vehicle Detection, automatic, circular SAR

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4 Modified Acetamidobenzoxazolone Based Biomarker for Translocator Protein Mapping during Neuroinflammation

Authors: Neelam Kumari, Anjani Kumar Tiwari, Anil Mishra


The 18-kDa translocator protein (TSPO) previously called as peripheral benzodiazepine receptor, is proven biomarker for variety of neuroinflammation. TSPO is tryptophane rich five transmembranal protein found on outer mitochondrial membrane of steroid synthesising and immunomodulatory cells. In case of neuronal damage or inflammation the expression level of TSPO get upregulated as an immunomodulatory response. By utilizing Benzoxazolone as a basic scaffold, series of TSPO ligands have been designed followed by their screening through in silico studies. Synthesis has been planned by employing convergent methodology in six high yielding steps. For the synthesized ligands the ‘in vitro’ assay was performed to determine the binding affinity in term of Ki. On ischemic rat brain, autoradiography studies were also carried to check the specificity and affinity of the designed radiolabelled ligand for TSPO.Screening was performed on the basis of GScore of CADD based schrodinger software. All the modified and better prospective compound were successfully carried out and characterized by spectroscopic techniques (FTIR, NMR and HRMS). In vitro binding assay showed best binding affinity Ki = 6.1+ 0.3 for TSPO over central benzodiazepine receptor (CBR) Ki > 200. ARG studies indicated higher uptake of two analogues on the lesion side compared with that on the non-lesion side of ischemic rat brains. Displacement experiments with unlabelled ligand had minimized the difference in uptake between the two sides which indicates the specificity of the ligand towards TSPO receptor.

Keywords: Imaging, PET, TSPO, Acetamidobenzoxazolone

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3 Procedure to Use Quantitative Bone-Specific SPECT/CT in North Karelia Central Hospital

Authors: L. Korpinen, P. Taskinen, P. Rautio


This study aimed to describe procedures that we developed to use in the quantitative, bone-specific SPECT/CT at our hospital. Our procedures included the following questions for choosing imaging protocols, which were based on a clinical doctor's referral: (1) Is she/he a cancer patient or not? (2) Are there any indications of inflammatory rheumatoid arthritis? We performed about 1,106 skeletal scintigraphies over two years. About 394 patients were studied with quantitative bone-specific single-photon emission computed tomography/computerized tomography (SPECT/CT) (i.e., about 36% of all bone scintigraphies). Approximately 64% of the patients were studied using the conventional Anterior-Posterior/Posterior-Anterior imaging. Our procedure has improved efficiency and decreased cycle times.

Keywords: Imaging, procedure, skeletal scintigraphy, SPECT/CT

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2 Coherent Optical Tomography Imaging of Epidermal Hyperplasia in Vivo in a Mouse Model of Oxazolone Induced Atopic Dermatitis

Authors: Eric Lacoste


Laboratory animals are currently widely used as a model of human pathologies in dermatology such as atopic dermatitis (AD). These models provide a better understanding of the pathophysiology of this complex and multifactorial disease, the discovery of potential new therapeutic targets and the testing of the efficacy of new therapeutics. However, confirmation of the correct development of AD is mainly based on histology from skin biopsies requiring invasive surgery or euthanasia of the animals, plus slicing and staining protocols. However, there are currently accessible imaging technologies such as Optical Coherence Tomography (OCT), which allows non-invasive visualization of the main histological structures of the skin (like stratum corneum, epidermis, and dermis) and assessment of the dynamics of the pathology or efficacy of new treatments. Briefly, female immunocompetent hairless mice (SKH1 strain) were sensitized and challenged topically on back and ears for about 4 weeks. Back skin and ears thickness were measured using calliper at 3 occasions per week in complement to a macroscopic evaluation of atopic dermatitis lesions on back: erythema, scaling and excoriations scoring. In addition, OCT was performed on the back and ears of animals. OCT allows a virtual in-depth section (tomography) of the imaged organ to be made using a laser, a camera and image processing software allowing fast, non-contact and non-denaturing acquisitions of the explored tissues. To perform the imaging sessions, the animals were anesthetized with isoflurane, placed on a support under the OCT for a total examination time of 5 to 10 minutes. The results show a good correlation of the OCT technique with classical HES histology for skin lesions structures such as hyperkeratosis, epidermal hyperplasia, and dermis thickness. This OCT imaging technique can, therefore, be used in live animals at different times for longitudinal evaluation by repeated measurements of lesions in the same animals, in addition to the classical histological evaluation. Furthermore, this original imaging technique speeds up research protocols, reduces the number of animals and refines the use of the laboratory animal.

Keywords: Imaging, Atopic dermatitis, Histology, mouse model, oxzolone model

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1 Computational Approaches to Study Lineage Plasticity in Human Pancreatic Ductal Adenocarcinoma

Authors: Almudena Espin Perez, Tyler Risom, Carl Pelz, Isabel English, Robert M. Angelo, Rosalie Sears, Andrew J. Gentles


Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly malignancies. The role of the tumor microenvironment (TME) is gaining significant attention in cancer research. Despite ongoing efforts, the nature of the interactions between tumors, immune cells, and stromal cells remains poorly understood. The cell-intrinsic properties that govern cell lineage plasticity in PDAC and extrinsic influences of immune populations require technically challenging approaches due to the inherently heterogeneous nature of PDAC. Understanding the cell lineage plasticity of PDAC will improve the development of novel strategies that could be translated to the clinic. Members of the team have demonstrated that the acquisition of ductal to neuroendocrine lineage plasticity in PDAC confers therapeutic resistance and is a biomarker of poor outcomes in patients. Our approach combines computational methods for deconvolving bulk transcriptomic cancer data using CIBERSORTx and high-throughput single-cell imaging using Multiplexed Ion Beam Imaging (MIBI) to study lineage plasticity in PDAC and its relationship to the infiltrating immune system. The CIBERSORTx algorithm uses signature matrices from immune cells and stroma from sorted and single-cell data in order to 1) infer the fractions of different immune cell types and stromal cells in bulked gene expression data and 2) impute a representative transcriptome profile for each cell type. We studied a unique set of 300 genomically well-characterized primary PDAC samples with rich clinical annotation. We deconvolved the PDAC transcriptome profiles using CIBERSORTx, leveraging publicly available single-cell RNA-seq data from normal pancreatic tissue and PDAC to estimate cell type proportions in PDAC, and digitally reconstruct cell-specific transcriptional profiles from our study dataset. We built signature matrices and optimized by simulations and comparison to ground truth data. We identified cell-type-specific transcriptional programs that contribute to cancer cell lineage plasticity, especially in the ductal compartment. We also studied cell differentiation hierarchies using CytoTRACE and predict cell lineage trajectories for acinar and ductal cells that we believe are pinpointing relevant information on PDAC progression. Collaborators (Angelo lab, Stanford University) has led the development of the Multiplexed Ion Beam Imaging (MIBI) platform for spatial proteomics. We will use in the very near future MIBI from tissue microarray of 40 PDAC samples to understand the spatial relationship between cancer cell lineage plasticity and stromal cells focused on infiltrating immune cells, using the relevant markers of PDAC plasticity identified from the RNA-seq analysis.

Keywords: Imaging, Microenvironment, deconvolution, PDAC

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