Molecular Imaging of Inflammation in Aortic Aneurysmal Disease

The high mortality rate of diseases of the aorta has its foundation in imaging methods that define anatomy and disease burden but less so upon the diagnosis of asymptomatic conditions, rate of aneurysm expansion, or prediction of rupture. However, anatomical features can now be co-localized with molecular and physiological activity. The advancement of nanoparticles based upon iron oxide will also serve to bring a trio of magnetic, radionuclide, and optical imaging modalities together. The combinations of these technologies are still at the preclinical refinement stage but already enzyme-activatable probes have b

F-19-nanoparticles: platform for in vivo delivery of fluorinated biomaterials for F-19-MRI

Fluorine-19 (F-19) magnetic resonance imaging (MRI) features one of the most investigated and innovative techniques for quantitative and unambiguous cell tracking, providing information for both localization and number of cells. Because of the relative insensitivity of the MRI technique, a high number of magnetically equivalent fluorine atoms are required to gain detectable signals. However, an increased amount of F-19 nuclei induces low solubility in aqueous solutions, making fluorine-based probes not suitable for in vivo imaging applications. In this context, nanoparticle-based platforms play a crucial role, since nanoparticles may carry a high payload of F-19-based contrast agents into the relevant cells or tissues, increase the imaging agents biocompatibility, and provide a highly versatile platform. In this review, we present an overview of the F-19-based nanoprobes for sensitive F-19-MRI, focusing on the main nanotechnologies employed to date, such as fluorine and theranostic nanovectors, including their design and applications.Cardiovascular Aspects of Radiolog

Optimized Longitudinal Monitoring of Stem Cell Grafts in Mouse Brain Using a Novel Bioluminescent/Near Infrared Fluorescent Fusion Reporter

Biodistribution and fate of transplanted stem cells via longitudinal monitoring has been successfully achieved in the last decade using optical imaging

Identification of receptor-type protein tyrosine phosphatase μ as a new marker for osteocytes

Osteocytes are the predominant cells in bone, where they form a cellular network and display important functions in bone homeostasis, phosphate metabolism and mechanical transduction. Several proteins strongly expressed by osteocytes are involved in these processes, e.g., sclerostin, DMP-1, PHEX, FGF23 and MEPE, while others are upregulated during differentiation of osteoblasts into osteocytes, e.g., osteocalcin and E11. The receptor-type protein tyrosine phosphatase µ (RPTPμ) has been described to be expressed in cells which display a cellular network, e.g., endothelial and neuronal cells, and is implied in mechanotransduction. In a capillary outgrowth assay using metatarsals derived from RPTPμ-knock-out/LacZ knock-in mice, we observed that the capillary structures grown out of the metatarsals were stained blue, as expected. Surprisingly, cells within the metatarsal bone tissue were positive for LacZ activity as well, indicating that RPTPμ is also expressed by osteocytes. Subsequent histochemical analysis showed that within bone, RPTPμ is expressed exclusively in early-stage osteocytes. Analysis of bone marrow cell cultures revealed that osteocytes are present in the nodules and an enzymatic assay enabled the quantification of the amount of osteocytes. No apparent bone phenotype was observed when tibiae of RPTPμ-knock-out/LacZ knock-in mice were analyzed by μCT at several time points during aging, although a significant reduction in cortical bone was observed in RPTPμ-knock-out/LacZ knock-in mice at 20 weeks. Changes in trabecular bon

Pre-clinical Evaluation of a Cyanine-Based SPECT Probe for Multimodal Tumor Necrosis Imaging

Purpose: Recently we showed that a number of carboxylated near-infrared fluorescent (NIRF) cyanine dyes possess strong necrosis avid properties in vitro as well as in different mouse models of spontaneous and therapy-induced tumor necrosis, indicating their potential use for cancer diagnostic- and prognostic purposes. In the previous study, the detection of the cyanines was achieved by whole body optical imaging, a technique that, due to the limited penetration of near-infrared light, is not suitable for investigations deeper than 1 cm within the human body. Therefore, in order to facilitate clinical translation, the purpose of the present study was to generate a necrosis avid cyanine-based NIRF probe that could also be used for single photon emission computed tomography (SPECT). For this, the necrosis avid NIRF cyanine HQ4 was radiolabeled with 111indium, via the chelate diethylene triamine pentaacetic acid (DTPA). Procedures: The necrosis avid properties of the radiotracer [111In]DTPA-HQ4 were examined in vitro and in vivo in different breast tumor models in mice using SPECT and optical imaging. Moreover, biodistribution studies were performed to examine the pharmacokinetics of the probe in vivo. Results: Using optical imaging and radioactivity measurements, in vitro, we showed selective accumulation of [111In]DTPA-HQ4 in dead cells. Using SPECT and in biodistribution studies, the necrosis avidity of the radiotracer was confirmed in a 4T1 mouse breast cancer model of spontaneous tumor necrosis and in a MCF-7 human breast cancer model of chemotherapy-induced tumor necrosis. Conclusions: The radiotracer [111In]DTPA-HQ4 possessed strong and selective necrosis avidity in vitro and in various mouse models of tumor necrosis in vivo, indicating its potential to be clinically applied for diagnostic purposes and to monitor anti-cancer treatment efficacy

A novel luciferase fusion protein for highly sensitive optical imaging: from single-cell analysis to in vivo whole-body bioluminescence imaging

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Optical advances in skeletal imaging applied to bone metastases

Optical Imaging has evolved into one of the standard molecular imaging modalities used in pre-clinical cancer research. Bone research however, strongly depends on other imaging modalities such as SPECT, PET, x-ray and μCT. Each imaging modality has its own specific strengths and weaknesses concerning spatial resolution, sensitivity and the possibility to quantify the signal. An increasing number of bone specific optical imaging models and probes have been developed over the past years. This review gives an overview of optical imaging modalities, models and probes that can be used to study skeletal complications of cancer in small laboratory animals.Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Multi-modality imaging and quantification of the effect of microtubule disrupting agent 2ME2-1198 on breast cancer progression in bone and subsequent osteolysis in a bioluminescent mouse model of metastatic bone disease

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

2-Methoxyestradiol Analogue ENMD-1198 Reduces Breast Cancer-Induced Osteolysis and Tumor Burden Both In Vitro and In Vivo

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

A method to follow tumor growth and tumor induced bone loss simultaneously over time, in vivo, using whole body bioluminescence fluorescence imaging

Bone and mineral researc