Bimodal Imaging Contrast Agent Research Articles

Synthesis of I@MPA-Mn:ZnSe as an efficient contrast agent for CT/fluorescence bi-modal imaging application

Bi-modal imaging contrast agent has attracted considerable attention in medical physics research field via quantum dots (QDs) fabrications. Doped quantum dots are playing an important role in seeking alternatives to conventional heavy metal-containing particles for medical applications. In order to improve imaging diagnosis, herein we report the design and synthesis of I@MPA-Mn:ZnSe as an efficient contrast agent. The medium, mercaptopropionic acid (MPA) capped Mn:ZnSe QDs surface-conjugated with a commercial contrast agent (Iohexol), was synthesized in seeking to overcome the limitations of Iohexol, also towards advancing bi-modal imaging approaches. In this study, morphology, elemental, absorption and fluorescence analysis were investigated, followed by a preliminary study of CT contrast enhancement and cell viability. In comparison to Iohexol, the fluorescence of I@MPA-Mn:ZnSe is observed at 585 nm. The CT Hounsfield unit (HU) increases linearly with mass concentration, with a four-fold increment in HU over that of Iohexol, producing greater than 328 ΔHU at similar concentrations, confirming the CT contrast efficiency of I@MPA-Mn:ZnSe. Cytotoxicity studies have confirmed that the medium possesses good biocompatibility and low toxicity to cells (HepG2 and MDA-MB-321). Present results for CT enhancement and brightness of fluorescence of I@MPA-Mn:ZnSe point to its great potential as a bi-modal contrast medium for further diagnosis applications.

Structure of CoFe2O4@CdTe nanocomposite with core/shell structure for high-performance Bi-modal imaging

A novel bi-modal imaging contrast agent was fabricated by depositing a layer of CdTe on the surface of CoFe2O4 nanoparticle, and applications for optical-MRI bi-modal imaging were investigated. The core/shell structure of the obtained nanocomposite was verified by TEM. TGA and nuclear magnetic relaxation dispersion (NMRD) profiles were applied for the deposition study. The in-vivo and in-vitro results showed that the deposition of CdTe layer can evidently improve the relaxivity of CoFe2O4 nanoparticle, which was investigated and explained by a “cation migration” theory. The as-synthesized compound is a promising nanocomposite for high performance bi-modal imaging applications.

Convenient and effective ICGylation of magnetic nanoparticles for biomedical applications

Nanoprobes used for biomedical applications usually require surface modifications with amphiphilic surfactants or inorganic coating materials to enhance their biocompatibility. We proposed a facile synthetic approach for the phase transfer of hydrophobic magnetic nanoparticles by the direct adherence of fluorescent probes, without any chemical modifications, for use as a magnetic resonance (MR)/near-infrared (NIR) fluorescence bimodal imaging contrast agent. Indocyanine green (ICG) was used not only as an optical component for NIR imaging, but also as a surfactant for phase transfer with no superfluous moiety: we therefore called the process “ICGylation”. Cell labeling and tracking in vivo with ICGylated magnetic nanoparticles were successfully performed by MR/NIR dual-mode imaging for three days, which showed remarkable biostability without any additional surface functionalization. We expect that this novel MR/NIR contrast agent demonstrating sensitive detection and simultaneous imaging capability can be used in diverse fields, such as the imaging and tracking of immune cells to confirm immunotherapeutic efficacy. The approach used could also be applied to other kinds of nanoparticles, and it would promote the development of advanced functional multimodal nanobioprobes.

Silica-Based Nanoparticles as Bifunctional and Bimodal Imaging Contrast Agents.

New bifunctional and bimodal nanoparticles (NPs) have been elaborated and characterised. They are based on silica NPs that incorporate a silylated ruthenium tris-bipyridine complex. The resulting suspension of amine-modified NPs with diameters of 20 nm was post-functionalised with a stable gadolinium ion complex. Interest in these NPs lies mainly in the confinement of optical and magnetic imaging agents (Ru and Gd complexes, respectively) within the NP volume. Their potential use as a bimodal probe (luminescence/magnetic resonance imaging) and theranostic agent (photodynamic therapy/imaging) is described. The biological potential of these NPs has been studied on HCT-116 cells and microscopy and cytotoxicity results are given.

Albumin-Mediated Biomineralization of Paramagnetic NIR Ag2S QDs for Tiny Tumor Bimodal Targeted Imaging in Vivo.

Bimodal imaging has captured increasing interests due to its complementary characteristics of two kinds of imaging modalities. Among the various dual-modal imaging techniques, MR/fluorescence imaging has been widely studied owing to its high 3D resolution and sensitivity. There is, however, still a strong demand to construct biocompatible MR/fluorescence contrast agents with near-infrared (NIR) fluorescent emissions and high relaxivities. In this study, BSA-DTPA(Gd) derived from bovine serum albumin (BSA) as a novel kind of biotemplate is employed for biomineralization of paramagnetic NIR Ag2S quantum dots (denoted as Ag2S@BSA-DTPA(Gd) pQDs). This synthetic strategy is found to be bioinspired, environmentally benign, and straightforward. The obtained Ag2S@BSA-DTPA(Gd) pQDs have fine sizes (ca. 6 nm) and good colloidal stability. They exhibit unabated NIR fluorescent emission (ca. 790 nm) as well as high longitudinal relaxivity (r1 = 12.6 mM(-1) s(-1)) compared to that of commercial Magnevist (r1 = 3.13 mM(-1) s(-1)). In vivo tumor-bearing MR and fluorescence imaging both demonstrate that Ag2S@BSA-DTPA(Gd) pQDs have pronounced tiny tumor targeting capability. In vitro and in vivo toxicity study show Ag2S@BSA-DTPA(Gd) pQDs are biocompatible. Also, biodistribution analysis indicates they can be cleared from body mainly via liver metabolism. This protein-mediated biomineralized Ag2S@BSA-DTPA(Gd) pQDs presents great potential as a novel bimodal imaging contrast agent for tiny tumor diagnosis.

Facile Synthesis of Gd-Cu-In-S/ZnS Bimodal Quantum Dots with Optimized Properties for Tumor Targeted Fluorescence/MR In Vivo Imaging.

Dual-modal imaging techniques have gained intense attention for their potential role in the dawning era of tumor early accurate diagnosis. Chelate-free robust dual-modal imaging nanoprobes with high efficiency and low toxicity are of essential importance for tumor targeted dual-modal in vivo imaging. It is still a crucial issue to endow Cd-free dual-modal nanoprobes with bright fluorescence as well as high relaxivity. Herein, a facile synthetic strategy was developed to prepare Gd-doped CuInS/ZnS bimodal quantum dots (GCIS/ZnS, BQDs) with optimized properties. The fluorescent properties of the GCIS/ZnS BQDs can be thoroughly optimized by varying reaction temperature, aging time, and ZnS coating. The amount of Gd precursor can be well-controlled to realize the optimized balance between the MR relaxivity and optical properties. The obtained hydrophobic GCIS/ZnS BQDs were surface engineered into aqueous phase with PEGylated dextran-stearyl acid polymeric lipid vesicles (PEG-DS PLVs). Upon the phase transfer, the hydrophilic GCIS/ZnS@PLVs exhibited pronounced near-infrared fluorescence as well as high longitudinal relaxivity (r1 = 9.45 mM(-1) S(-1)) in water with good colloidal stability. In vivo tumor-bearing animal experiments further verified GCIS/ZnS@PLVs could achieve tumor-targeted MR/fluorescence dual-modal imaging. No toxicity was observed in the in vivo and ex vivo experiments. The GCIS/ZnS@PLVs present great potential as bimodal imaging contrast agents for tumor diagnosis.

Microbubble embedded with upconversion nanoparticles as a bimodal contrast agent for fluorescence and ultrasound imaging

Bimodal imaging offers additional imaging signal thus finds wide spread application in clinical diagnostic imaging. Fluorescence/ultrasound bimodal imaging contrast agent using fluorescent dyes or quantum dots for fluorescence signal has emerged as a promising method, which however requires visible light or UV irradiation resulting in photobleaching, photoblinking, auto-fluorescence and limited tissue penetration depth. To surmount these problems, we developed a novel bimodal contrast agent using layer-by-layer assembly of upconversion nanoparticles onto the surface of microbubbles. The resulting microbubbles with average size of 2 μm provide enhanced ultrasound echo for ultrasound imaging and upconversion emission upon near infrared irradiation for fluorescence imaging. The developed bimodal contrast agent holds great potential to be applied in ultrasound target technique for targeted diseases diagnostics and therapy.

β-conjugation of gadolinium(III) DOTA complexes to zinc(II) porpholactol as potential multimodal imaging contrast agents

Synthesis of two bimodal imaging agents consist of a hydrophobic zinc(II) tetrapentafluorophenylporpholactol core and a β-substituted hydrophilic Gd ( III ) DO3A (ZnLGd539) or DOTA (ZnLGd595) like moiety has been described (DO3A = 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid, DOTA = 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). Through β-conjugation approach, the absorption at deep red region increases compared to traditional conjugation methods at meso-position. More importantly, these new complexes possess largely improved ionic relaxitivites relative to the sole Gd ( III ) magnetic resonance imaging (MRI) agents such as Gd ( III ) DO3A and Gd ( III ) DOTA like complexes. Combining the optical and magnetic resonance measurements in aqueous media, the largely enhanced r1 relaxivities was attributed to the aggregation of ZnLGd539 and ZnLGd595 in aqueous media. Furthermore, fluorescence and magnetic resonance imaging experiment showed that both ZnLGd539 and ZnLGd595 can be applied as potential bimodal imaging contrast agents. Finally, both compounds showed no dark cytotoxicity and good photocytotoxicity (IC50 = 1.73 ± 0.13 and 1.52 ± 0.10 μM for ZnLGd539 and ZnLGd595 respectively) on Hela cells.

Bimodal Perfluorocarbon Nanoemulsions for Nasopharyngeal Carcinoma Targeting

The aim of this study was to perform the detection of folate receptor (FR)-positive tumors with a bimodal imaging contrast agent, a perfluorocarbon (PFC)/rhodamine nanoemulsion, providing both 19F-based magnetic resonance imaging (MRI) and fluorescence imaging capabilities. The PFC/rhodamine nanoemulsion was further infused with phospholipid-anchored folate to improve the ability to target FR-expressing tumors. The preferential accumulation of the FR-targeted bimodal nanoemulsion in FR-positive tumor sites was monitored by both 19F-MRI and optical imaging. The FR-targeted PFC nanoemulsion had no significant effect on cell viability, and the size and fluorescence signal of PFC nanoemulsion were very stable. These nanoprobes were successfully delivered into FR-positive tumor xenograft models and showed significantly enhanced signal intensities of 19F-MRI and fluorescence imaging in the tumor area. The folate-PFC/rhodamine nanoemulsion has a great potential to serve as a useful optical and 19F-MRI agent for the diagnosis and targeting of FR-positive tumor.

Lanthanide-DTPA grafted silica nanoparticles as bimodal-imaging contrast agents

The design and synthesis of a combined MRI-optical probe for bio-imaging are reported. The materials studied join the properties of lanthanide (Ln 3+) complexes and nanoparticles (NPs), offering an excellent solution for bimodal imaging. The hybrid SiO 2@APS/DTPA:Gd:Ln (Ln = Eu 3+ or Tb 3+) (APS: 3-aminopropyltriethoxysilane, DTPA: diethylenetriamine pentaacetic acid) system increases the payload of the active magnetic centre (Gd 3+) and introduces a Ln 3+ long-life excited state (Eu 3+: 0.35 ± 0.02 ms, Tb 3+: 1.87 ± 0.02 ms), with resistance to photobleaching and sharp emission bands. The Eu 3+ ions reside in a single low-symmetry site. Although the photoluminescence emission is not influenced by the simultaneous presence of Gd 3+ and Eu 3+, a moderate r 1 increase and a larger enhancement of r 2 are observed, particularly at high fields, due to susceptibility effects on r 2. The presence of Tb 3+ instead of Eu 3+ further raises r 1 but decreases r 2. These values are constant over a wide (5–13) pH range, indicating the paramagnetic NPs stability and absence of leaching. The uptake of NPs by living cells is fast and results in an intensity increase in the T 1-weighted MRI images. The optical properties of the NPs in cellular pellets are also studied, confirming their potential as bimodal imaging agents.

New potential bimodal imaging contrast agents based on DOTA-like and porphyrin macrocycles

A bifunctional chelator featuring (DO3A-AM)-Porphyrin units has been prepared. The high-field relaxivity of the Gd complex is similar to those of currently available contrast agents clearly showing that the first coordination sphere remains identical to the parent molecule [Gd(DO3A-AM)(H2O)], with one coordinated water molecule.

Perfluorodecalin/[InGaP/ZnS quantum dots] nanoemulsions as 19F MR/optical imaging nanoprobes for the labeling of phagocytic and nonphagocytic immune cells

Multimodal imaging contrast agents with unique magnetic resonance (MR) and optical imaging capabilities have great potentials in the diagnosis and therapy of disease. Using a rational materials design approach, the bimodal imaging contrast agent, perfluorodecalin (PFD)/[InGaP/ZnS quantum dots (QDs)] composite nanoemulsions is developed in this study. 19F molecules in the PFD/[InGaP/ZnS QDs] nanoemulsions provide a 19F-based MR imaging capability, while fluorescent QDs dispersed in PFD nanodroplets provide an optical imaging modality. This study also demonstrates that these bimodal imaging contrast agents can be delivered easily into both phagocytic and nonphagocytic immune cells. Internalization of multifunctional PFD/[InGaP/ZnS QDs] nanoemulsions into immunotherapeutic cells permits the labeled cells to be imaged by both magnetic resonance and fluorescence imaging with little effect on cell viability and function. The results of our study highlight the potential of PFD/[InGaP/ZnS QDs] nanoemulsion as a bimodal imaging nanoprobe for molecular imaging in immune cell-based cancer therapies.

Multifunctional Silica Nanocapsule with a Single Surface Hole

Multifunctional silica nanocapsules containing magnetic nanoparticles and fluorescent quantum dots with a single surface hole fabricated by a single-step emulsion-mediated process are described. The silica nanocapsules (see images) are easily internalized by phagocytic dendritic cells and show a high potential as bimodal imaging contrast agents (for fluorescence and magnetic resonance imaging) in vivo as well as in vitro.

Plasmonic Magnetic Nanostructure for Bimodal Imaging and Photonic‐Based Therapy of Cancer Cells

Two in one. Multifunctional hollow-type gold nanostructures that encapsulate iron oxide nanoparticles have been developed for biomedical imaging and targeted cancer therapy applications. The combination of the magnetic character of iron oxide nanoparticles with the near-infrared-light-absorbing (and scattering) gold nanostructures rendered the synthesized nanoparticles useful as bimodal imaging contrast agents (for MRI and optical imaging) as well as for photonic-based therapeutic materials.