Standard Radio-Iodine Labeling Protocols Impaired the Functional Integrity of Mesenchymal Stem/Stromal Cell Exosomes.

Mesenchymal stem/stromal cells (MSCs) are an extensively studied cell type in clinical trials due to their easy availability, substantial ex vivo proliferative capacity, and therapeutic efficacy in numerous pre-clinical animal models of disease. The prevailing understanding suggests that their therapeutic impact is mediated by the secretion of exosomes. Notably, MSC exosomes present several advantages over MSCs as therapeutic agents, due to their non-living nature and smaller size.

Radiolabeled Liposomes for Nuclear Imaging Probes.

Quantitative nuclear imaging techniques are in high demand for various disease diagnostics and cancer theranostics. The non-invasive imaging modality requires radiotracing through the radioactive decay emission of the radionuclide. Current preclinical and clinical radiotracers, so-called nuclear imaging probes, are radioisotope-labeled small molecules.

Radiochemical Feasibility of Mixing of Tc-MAA and Y-Microspheres with Omnipaque Contrast.

Yttrium-90 (Y) microspheres are widely used for the treatment of liver-dominant malignant tumors. They are infused via catheter into the hepatic artery branches supplying the tumor under fluoroscopic guidance based on pre-therapy angiography and Technetium-99m macroaggregated albumin (Tc-MAA) planning. However, at present, these microspheres are suspended in radiolucent media such as dextrose 5% (D5) solution.

Nanomaterial Probes for Nuclear Imaging.

Nuclear imaging is a powerful non-invasive imaging technique that is rapidly developing in medical theranostics. Nuclear imaging requires radiolabeling isotopes for non-invasive imaging through the radioactive decay emission of the radionuclide. Nuclear imaging probes, commonly known as radiotracers, are radioisotope-labeled small molecules.

Positron emission tomographic imaging in drug discovery.

Positron emission tomography (PET) is an extensively used nuclear functional imaging technique, especially for central nervous system (CNS) and oncological disorders. Currently, drug development is a lengthy and costly pursuit. Imaging with PET radiotracers could be an effective way to hasten drug discovery and advancement, because it facilitates the monitoring of key facets, such as receptor occupancy quantification, drug biodistribution, pharmacokinetic (PK) analyses, validation of target engagement, treatment monitoring, and measurement of neurotransmitter concentrations.

An In Vivo Study of a Rat Fluid-Percussion-Induced Traumatic Brain Injury Model with [C]PBR28 and [F]flumazenil PET Imaging.

Traumatic brain injury (TBI) modelled by lateral fluid percussion-induction (LFPI) in rats is a widely used experimental rodent model to explore and understand the underlying cellular and molecular alterations in the brain caused by TBI in humans. Current improvements in imaging with positron emission tomography (PET) have made it possible to map certain features of TBI-induced cellular and molecular changes equally in humans and animals. The PET imaging technique is an apt supplement to nanotheranostic-based treatment alternatives that are emerging to tackle TBI.

Dealing with PET radiometabolites.

Positron emission tomography (PET) offers the study of biochemical, physiological, and pharmacological functions at a cellular and molecular level. The performance of a PET study mostly depends on the used radiotracer of interest. However, the development of a novel PET tracer is very difficult, as it is required to fulfill a lot of important criteria.

Gadolinium-based bimodal probes to enhance T1-Weighted magnetic resonance/optical imaging.

Gd-based contrast agents have been extensively used for signal enhancement of T-weighted magnetic resonance imaging (MRI) due to the large magnetic moment and long electron spin relaxation time of the paramagnetic Gd ion. The key requisites for the development of Gd-based contrast agents are their relaxivities and stabilities which can be achieved by chemical modifications. These modifications include coordinating Gd with a chelator such as diethylenetriamine pentaacetic acid (DTPA) or 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), encapsulating Gd in nanoparticles, conjugation to biomacromolecules such as polymer micelles and liposomes, or non-covalent binding to plasma proteins.

Activatable Cell-Penetrating Peptide Conjugated Polymeric Nanoparticles with Gd-Chelation and Aggregation-Induced Emission for Bimodal MR and Fluorescence Imaging of Tumors.

Activatable cell-penetrating peptide (ACPP) conjugated polymeric nanoparticles containing gadolinium (Gd)-chelates and aggregation-induced emission fluorogens (AIEgens) have been synthesized and applied as a magnetic resonance imaging (MRI) and fluorescence imaging (FI) bimodal imaging probe with active tumor targeting. The polymeric nanoparticles have been generated by dissolving presynthesized linear block copolymers into water directly. With AIEgens, N-BP5-Gd-ACPPs showed tumor cell penetration, which can be characterized by FI.

PET-MR and SPECT-MR multimodality probes: Development and challenges.

Positron emission tomography (PET)-magnetic resonance (MR) or single photon emission computed tomography (SPECT)-MR hybrid imaging is being used in daily clinical practice. Due to its advantages over stand-alone PET, SPECT or MR imaging, in many areas such as oncology, the demand for hybrid imaging techniques is increasing dramatically. The use of multimodal imaging probes or biomarkers in a single molecule or particle to characterize the imaging subjects such as disease tissues certainly provides us with more accurate diagnosis and promotes therapeutic accuracy.

Simplified estimation of binding parameters based on image-derived reference tissue models for dopamine transporter bindings in non-human primates using [F]FE-PE2I and PET.

The aim of this study on dopamine transporter binding by [F]FE-PE2I and PET was to describe an image-derived approach using reference tissue models: the Logan DVR approach and simplified reference tissue model (SRTM), the features of which were simple to operate and precise in the measurements. Using the approach, the authors sought to obtain binding images and parameters. [F]FE-PE2I and dynamic PET as well as an MRI was performed on three rhesus monkeys, and metabolite corrected arterial plasma inputs were obtained.

Synthesis and in vivo magnetic resonance imaging evaluation of biocompatible branched copolymer nanocontrast agents.

Branched copolymer nanoparticles (D(h) =20-35 nm) possessing 1,4,7, 10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid macrocycles within their cores have been synthesized and applied as magnetic resonance imaging (MRI) nanosized contrast agents in vivo. These nanoparticles have been generated from novel functional monomers via reversible addition-fragmentation chain transfer polymerization. The process is very robust and synthetically straightforward.

Pharmacokinetics of Gd(DO3A-Lys) and MR imaging studies in an orthotopic U87MG glioma tumor model.

Pharmacokinetics of Gd(DO3A-Lys), a macrocyclic gadolinium-based magnetic resonance imaging (MRI) contrast agent functionalized with a lysine derivative, was studied in Wistar rats. Kinetic data were fitted using a two-compartment model and revealed Gd(DO3A-Lys) to have a distribution half-life, t1/2 (α), of 1.3 min, an elimination half-life, t1/2 (β), of 24.

Negative contrast Cerenkov luminescence imaging of blood vessels in a tumor mouse model using [68Ga]gallium chloride.

Background: Cerenkov luminescence imaging (CLI) is an emerging imaging technique where visible light emitted from injected beta-emitting radionuclides is detected with an optical imaging device. CLI research has mostly been focused on positive contrast imaging for ascertaining the distribution of the radiotracer in a way similar to other nuclear medicine techniques. Rather than using the conventional technique of measuring radiotracer distribution, we present a new approach of negative contrast imaging, where blood vessel attenuation of Cerenkov light emitted by [68Ga]GaCl3 is used to image vasculature.

Manipulating the surface coating of ultra-small Gd2O3 nanoparticles for improved T1-weighted MR imaging.

In this report, monodispersed ultra-small Gd2O3 nanoparticles capped with hydrophobic oleic acid (OA) were synthesized with average particle size of 2.9 nm. Two methods were introduced to modify the surface coating to hydrophilic for bio-applications.

An intravascular MRI contrast agent based on Gd(DO3A-Lys) for tumor angiography.

An intravascular MRI contrast agent Gd(DO3A-Lys), Gadolinium(III) (2,2',2″-(10-(3-(5-benzamido-6-methoxy-6-oxohexylamino)-3-oxopropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triyl)triacetate), has been studied for tumor angiography based on its high relaxivity and long blood half-life. The preparation procedures of the contrast agent have been modified in order to achieve higher yield and improve the synthetic reproducibility. High relaxivity of Gd(DO3A-Lys) has been confirmed by measurements at 3 T, 7 T and 9.

Gadolinium-functionalized aggregation-induced emission dots as dual-modality probes for cancer metastasis study.

Understanding the localization and engraftment of tumor cells at postintravasation stage of metastasis is of high importance in cancer diagnosis and treatment. Advanced fluorescent probes and facile methodologies for cell tracing play a key role in metastasis studies. In this work, we design and synthesize a dual-modality imaging dots with both optical and magnetic contrast through integration of a magnetic resonance imaging reagent, gadolinium(III), into a novel long-term cell tracing probe with aggregation-induced emission (AIE) in far-red/near-infrared region.

Gadolinium chelate with DO3A conjugated 2-(diphenylphosphoryl)-ethyldiphenylphosphonium cation as potential tumor-selective MRI contrast agent.

A series of organic cations, such as triphenylphosphonium (TPP), 2-(diphenylphosphoryl)-ethyldiphenylphosphonium (TPEP), represent molecular probes for imaging tumors. These organic cations have been labeled with ⁶⁴Cu radioisotope for imaging tumors by positron emission tomograghy (PET). Among these organic cation ligands, TPEP was selected for extensive evaluation using magnetic resonance imaging (MRI) based on its higher tumor uptake and better Tumor/Background (T/B) ratios.

Synthesis of manganese ferrite/graphene oxide nanocomposites for biomedical applications.

In this study, MnFe(2)O(4) nanoparticle (MFNP)-decorated graphene oxide nanocomposites (MGONCs) are prepared through a simple mini-emulsion and solvent evaporation process. It is demonstrated that the loading of magnetic nanocrystals can be tuned by varying the ratio of graphene oxide/magnetic nanoparticles. On top of that, the hydrodynamic size range of the obtained nanocomposites can be optimized by varying the sonication time during the emulsion process.

Silica nanocapsules of fluorescent conjugated polymers and superparamagnetic nanocrystals for dual-mode cellular imaging.

We describe here a facile and benign synthetic strategy to integrate the fluorescent behavior of conjugated polymers and superparamagnetic properties of iron oxide nanocrystals into silica nanocapsules, forming a new type of bifunctional magnetic fluorescent silica nanocapsule (BMFSN). The resultant BMFSNs are uniform, colloidally stable in aqueous medium, and exhibit the desired dual functionality of fluorescence and superparamagnetism in a single entity. Four conjugated polymers with different emissions were used to demonstrate the versatility of employing this class of fluorescent materials for the preparation of BMFSNs.

Development of intravascular contrast agents for MRI using gadolinium chelates.

Two MRI contrast agents (CAs) composed of Gd-DO3A conjugated to amino acid building blocks derived from glutamic acid (CA1) and lysine (CA2) have been synthesized by using novel alkyne and propionate linkers, and subsequently characterized. In vitro cell viability assays showed insignificant cytotoxicity of both CAs at low concentrations up to 0.2 mM.

Facile synthesis of water-stable magnetite nanoparticles for clinical MRI and magnetic hyperthermia applications.

Aims: Superparamagnetic magnetite nanoparticles have been under intensive investigation in nanomedicine. However, it is still a challenge to synthesize high-quality water-stable magnetite nanoparticles for better magnetic performance and less side effects in medical MRI and nanothermotherapy.

Materials & Methods: We successfully synthesized hydrophilic magnetite nanoparticles through thermal decomposition of Fe(acac)(3) in triethylene glycol, which were coated with a triethylene glycol layer and thus demonstrated excellent water stability.

Superparamagnetic iron oxide--loaded poly(lactic acid)-D-alpha-tocopherol polyethylene glycol 1000 succinate copolymer nanoparticles as MRI contrast agent.

We developed a strategy to formulate supraparamagnetic iron oxides (SPIOs) in nanoparticles (NPs) of biodegradable copolymer made up of poly(lactic acid) (PLA) and d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS) for medical imaging by magnetic resonance imaging (MRI) of high contrast and low side effects. The IOs-loaded PLA-TPGS NPs (IOs-PNPs) were prepared by the single emulsion method and the nanoprecipitation method. Effects of the process parameters such as the emulsifier concentration, IOs loading in the nanoparticles, and the solvent to non-solvent ratio on the IOs distribution within the polymeric matrix were investigated and the formulation was then optimized.

64Cu-labeled 2-(diphenylphosphoryl)ethyldiphenylphosphonium cations as highly selective tumor imaging agents: effects of linkers and chelates on radiotracer biodistribution characteristics.

Radiolabeled organic cations, such as triphenylphosphonium (TPP), represents a new class of radiotracers for imaging cancers and the transport function of multidrug resistance P-glycoproteins (particularly MDR1 Pgp) by single photon emission computed tomography (SPECT) or positron emission tomography (PET). This report presents the synthesis and biological evaluation of (64)Cu-labeled 2-(diphenylphosphoryl)ethyldiphenylphosphonium (TPEP) cations as novel PET radiotracers for tumor imaging. Biodistribution studies were performed using the athymic nude mice bearing subcutaneous U87MG human glioma xenografts to explore the impact of linkers, bifunctional chelators (BFCs), and chelates on biodistribution characteristics of the (64)Cu-labeled TPEP cations.