Molecular Imaging Applications Research Articles

Production of the next-generation positron nuclide zirconium-89 (89 Zr) guided by Monte Carlo simulation and its good quality for antibody labeling.

The next-generation positron zirconium-89 (89 Zr, T1/2 = 3.27 days) is a novel nuclide for immunological positron emission tomography because of its favorite longer half-life. The aim of this work is to develop optimized methods for routine production and purification of 89 Zr through Monte Carlo (MC) simulation and laboratory experiments. 89 Y(p,n)89 Zr reaction was used for 89 Zr production. Optimized thicknesses of Al degrader (0.11 cm) and 89 Y foil (0.064 cm) were simulated through MC method. 89 Zr (15.0-40.7 mCi) with an average production rate of 0.92 ± 0.12 mCi/μA·h was produced after 1- to 2-h bombardment at the proton beam energy of 20 MeV and current of 20 μA. High radio-purity 89 Zr (6.14-26.8 mCi) obtained eluted from hydroxamate resin using 1-mol/L oxalic acid solution, with the concentration of 2.7 × 104 mCi/L. The gamma spectrum showed that the characteristic peak of 89 Zr was 511 and 909 keV, and no impurities were found. [89 Zr]Zr-DFO-trastuzumab was successfully labeled and performed good radiochemical purity (>95%) and stability that showed potential application in tumor molecular imaging.

Zirconium nitride as a highly efficient nitrogen source to synthesize the metal nitride clusterfullerenes

Metal nitride clusterfullerenes (NCFs) have significant applications in molecular electronics, biomedical imaging, and nonlinear optical devices due to their unique structures. However, their wide applications are limited by the production quantity. In this work, the yields of metal nitride clusterfullerenes M3N@C80 (M=Y, Sc, Gd) were greatly enhanced by utilizing zirconium nitride (ZrN) as an efficient nitrogen source for the arc-discharge method. Compared with the traditional synthetic route using N2 gas as nitrogen source, the ZrN inside graphite tube can be vaporized simultaneously with metal and graphite, and then afford the high concentration of nitrogen atoms in the arc region, which will promote the formation of metal nitride clusterfullerenes finally. The ZrN can promote the yields of Y3N@C80, Sc3N@C80 and Gd3N@C80, revealing the universal applicability of ZrN as a highly efficient nitrogen source. Specifically, the yield of Sc3N@C80 was greatly improved when adding ZrN, and it shows over double yield compared to traditional synthetic route using N2 gas. In addition, ZrN can also enhance the yields of paramagnetic azametallofullerene M2@C79N due to the high concentration of nitrogen atoms in the arc region. This new method enhances the production quantity of metal nitride clusterfullerenes and azametallofullerenes, and it will greatly promote the research and application of these molecular carbon materials.

Implications of Biomolecular Corona for Molecular Imaging.

The development of nanoparticle probes has opened up new possibilities for molecular imaging in the era of precision medicine. There are a wide range of nanoprobes that are being used for various modalities that have demonstrated promising potential in early detection, disease monitoring, and theranostics. However, the rate ofsuccessfulclinical translation of the nanoprobes is very low and is affected by the lack of our understanding about nanoparticle interaction with biological fluids after systemic administration, thus representing an unmet clinical need. One of the poorly understood issues relates to the formation of biomolecular corona, a layer of biomolecules formed on the surface of nanoscale materials during their interactions with biological fluids. The biomolecular corona has several significant effects on the biodistribution of nanoprobes and their imaging ability by (i) reducing their targeting efficacy and (ii) affecting the intrinsic imaging properties (e.g., contrast capacity of magnetic nanoprobes). This review provides insights on the importance of considering biomolecular corona in the development of nanoprobes, which may enable their more efficient utilization for molecular imaging applications.

Preparation and Evaluation of New LAT1-Targeted USPION to Improve Sensitivity and Specificity in Metabolic Magnetic Imaging of Breast Cancer

The purpose of this study was the investigation of the targeting potential of tyrosine-conjugated ultra small superparamagnetic iron oxide nanoparticles (USPIONs) as a new targeted nano-contrast agent for application in molecular magnetic resonance imaging (MRI) of breast cancer. Recently, studies demonstrated that L-type amino acid transporters (LAT1) are highly expressed in breast cancer cells. Thus, LAT1 targeting via tyrosine as a LAT1 substrate could improve the sensitivity and specificity of this nanosized contrast agent. To achieve this goal, USPIONs were conjugated to tyrosine and characterized using DLS and FT-IR. The cell viability was measured in different concentrations of nanoparticles (0.6, 1.2, 2.4mM) in breast cancer cells (MDA231, MCF7,4T1) and control cell line (normal kidney cells; HEK293) with the MTT assay. Cellular uptake was evaluated via Prussian blue staining and Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES) as well as by measurement of the reduction of signal intensity using 3Tesla clinical MRI. T2-weighted imaging in tumor-bearing bulb/c mice was performed via brain coil and home-built phantom. The particle size and charge of USPIO significantly changed after the conjugation of tyrosine. According to ICP-OES results from the cellular uptake of tyrosine-USPION in 4T1 cell line and HEK-293was 48.14%±1.43, and 6.91±0.21, respectively. The reduction in MRI signal intensity at in vitro studies was higher in the presence of tyrosine-USPION than of USPION. The reduction in MRI signal intensity at in vivo studies was 58.83% in the presence of tyrosine conjugated USPION compared with plain nanoparticles. Biodistribution studies demonstrated that the accumulation of tyrosine-USPIONs was about seven times higher than that of non-targeted USPIONs after 24h. In conclusion, tyrosine-USPIO as a new LAT1 targeted contrast agent with high sensitivity and specificity can be suggested as a good and ideal candidate in breast cancer molecular imaging.

Rapidly (and Successfully) Translating Novel Brain Radiotracers From Animal Research Into Clinical Use.

The advent of preclinical research scanners for in vivo imaging of small animals has added confidence into the multi-step decision-making process of radiotracer discovery and development. Furthermore, it has expanded the utility of imaging techniques available to dissect clinical questions, fostering a cyclic interaction between the clinical and the preclinical worlds. Significant efforts from medicinal chemistry have also made available several high-affinity and selective compounds amenable for radiolabeling, that target different receptors, transporters and enzymes in vivo. This substantially increased the range of applications of molecular imaging using positron emission tomography (PET) or single photon emission computed tomography (SPECT). However, the process of developing novel radiotracers for in vivo imaging of the human brain is a multi-step process that has several inherent pitfalls and technical difficulties, which often hampers the successful translation of novel imaging agents from preclinical research into clinical use. In this paper, the process of radiotracer development and its relevance in brain research is discussed; as well as, its pitfalls, technical challenges and future promises. Examples of successful and unsuccessful translation of brain radiotracers will be presented.

Aggregation‐Induced Emission Luminogens for Direct Exfoliation of 2D Layered Materials in Ethanol

AbstractAggregation‐induced emission (AIE) luminogens are an important type of advanced functional materials with fantastic optical properties and have found potential applications in organic electronics, biochemistry, and molecular imaging. Herein, this article presents a novel application of AIE luminogens (AIEgens) for efficient exfoliation of layered transition metal dichalcogenides (TMDs, such as MoS2 and WSe2). From the 1H NMR spectroscopic analysis, the designed AIEgens can insert into the space between layers of MoS2 in ethanol solution and the dynamic molecular rotation against the weak interactions affords large‐scale few‐layer MoS2 nanosheets (7–8 layers) with enhanced smoothness. The 3D AIEgens play a significant role in preserving the crystal lattice of MoS2 even at high pressure (>15 GPa). More importantly, the new approach can also be used for exfoliation of WSe2 to achieve large‐scale few‐layer nanosheets. The present work thus provides a facile and high yielding synthetic method for accessing on a large scale 2D layered materials with enhanced properties for high‐technology applications.

Application and Prospects of Molecular Imaging in Immunotherapy.

Recently, immunotherapies that target the interactions of programmed cell death 1 (PD-1) with its major ligands, programmed death ligand 1 (PD-L1) and programmed death ligand 2 (PD-L2), have achieved significant success. To date, several immune checkpoint inhibitors targeting the PD-1/PD-L1 pathway have been developed to treat melanoma, non-small cell lung cancer, head and neck cancer, renal cell carcinoma, and urothelial carcinoma. Despite promising outcomes with immunotherapy, there are many limitations to several current immune biomarkers for predicting immune benefits and to traditional imaging for evaluating the efficacy and prognosis of immunotherapy and monitoring adverse reactions. In this review, we recommend a novel imaging method, molecular imaging. This paper reviews the application and prospects of molecular imaging in the context of current immunotherapies in regard to the following aspects: 1) detecting the expression of PD-1/PD-L1; 2) evaluating the efficacy of immunotherapy; 3) assessing patient prognosis with immunotherapy; 4) monitoring the toxicity of immunotherapy; and 5) other targets imaging.

Enzymatic Noncovalent Synthesis

Enzymatic reactions and noncovalent (i.e., supramolecular) interactions are two fundamental nongenetic attributes of life. Enzymatic noncovalent synthesis (ENS) refers to a process where enzymatic reactions control intermolecular noncovalent interactions for spatial organization of higher-order molecular assemblies that exhibit emergent properties and functions. Like enzymatic covalent synthesis (ECS), in which an enzyme catalyzes the formation of covalent bonds to generate individual molecules, ENS is a unifying theme for understanding the functions, morphologies, and locations of molecular ensembles in cellular environments. This review intends to provide a summary of the works of ENS within the past decade and emphasize ENS for functions. After comparing ECS and ENS, we describe a few representative examples where nature uses ENS, as a rule of life, to create the ensembles of biomacromolecules for emergent properties/functions in a myriad of cellular processes. Then, we focus on ENS of man-made (synthetic) molecules in cell-free conditions, classified by the types of enzymes. After that, we introduce the exploration of ENS of man-made molecules in the context of cells by discussing intercellular, peri/intracellular, and subcellular ENS for cell morphogenesis, molecular imaging, cancer therapy, and other applications. Finally, we provide a perspective on the promises of ENS for developing molecular assemblies/processes for functions. This review aims to be an updated introduction for researchers who are interested in exploring noncovalent synthesis for developing molecular science and technologies to address societal needs.

Reduction Triggered In Situ Polymerization in Living Mice.

"Smart" biomaterials that are responsive to physiological or biochemical stimuli have found many biomedical applications for tissue engineering, therapeutics, and molecular imaging. In this work, we describe in situ polymerization of activatable biorthogonal small molecules in response to a reducing environment change in vivo. We designed a carbohydrate linker- and cyanobenzothiazole-cysteine condensation reaction-based small molecule scaffold that can undergo rapid condensation reaction upon physiochemical changes (such as a reducing environment) to form polymers (pseudopolysaccharide). The fluorescent and photoacoustic properties of a fluorophore-tagged condensation scaffold before and after the transformation have been examined with a dual-modality optical imaging method. These results confirmed the in situ polymerization of this probe after both local and systemic administration in living mice.

Current Applications for Nuclear Medicine Imaging in Pulmonary Disease.

Purpose of ReviewThe main goal of the article is to familiarize the reader with commonly and uncommonly used nuclear medicine procedures that can significantly contribute to improved patient care. The article presents examples of specific modality utilization in the chest including assessment of lung ventilation and perfusion, imaging options for broad range of infectious and inflammatory processes, and selected aspects of oncologic imaging. In addition, rapidly developing new techniques utilizing molecular imaging are discussed.Recent FindingsThe article describes nuclear medicine imaging modalities including gamma camera, SPECT, PET, and hybrid imaging (SPECT/CT, PET/CT, and PET/MR) in the context of established and emerging clinical applications. Areas of potential future development in nuclear medicine are discussed with emphasis on molecular imaging and implementation of new targeted tracers used in diagnostics and therapeutics (theranostics).SummaryNuclear medicine and molecular imaging provide many unique and novel options for the diagnosis and treatment of pulmonary diseases. This article reviews current applications for nuclear medicine and molecular imaging and selected future applications for radiopharmaceuticals and targeted molecular imaging techniques.

Ultrasonic-Assisted Solid-Phase Peptide Synthesis of DOTA-TATE and DOTA-linker-TATE Derivatives as a Simple and Low-Cost Method for the Facile Synthesis of Chelator-Peptide Conjugates.

Peptides have been widely adopted as biological targeting vectors for applications in molecular imaging and peptide-receptor radionuclide therapy (PRRT). Somatostatin (SST) analogues such as octreotate (TATE) are exogenous ligands for somatostatin receptors (SSTRs), which are highly expressed on neuroendocrine tumors (NETs). Recently, both [68Ga]Ga-DOTA-TATE (NETSPOT) and [177Lu]Lu-DOTA-TATE (LUTATHERA) received U.S. Food and Drug Administration approval for positron emission tomography (PET) imaging and PRRT of NETs, respectively. However, to the best of our knowledge a well-described synthesis of DOTA-TATE has not been reported in the literature. Herein, we report a fully reoptimized DOTA-TATE synthesis, including the application of a simple ultrasonic bath to greatly improve yields, reduce coupling times, and decrease the amount of reagents required for each coupling step by a half. The most prevalently used cyclizing agents such as iodine, thallium(III) trifluoroacetate, hydrogen peroxide, and dimethyl sulfoxide were compared. On-resin cyclizations using mechanical agitation showed higher yields (23% and 25% using I2 and Tl(III), respectively) than off-resin (1.3% and 11% using DMSO and H2O2, respectively), and the total synthesis time of DOTA-TATE was ∼540 min excluding the cyclization step, with a total synthesis yield of ∼23%. The same manual SPPS methods/reagents were reoptimized with ultrasonic (US) agitation, resulting in an immense reduction in the total synthesis time by ∼8-fold to ∼70 min for DOTA-TATE with a higher yield (∼29% yield), and ∼13-fold to 105 min for DOTA-PEG4-TATE (∼29% yield). Also, the use of US agitation reduces the need for excess molar equivalents of the reagents to a half, which is particularly important when coupling expensive or custom-synthesized groups such as bifunctional chelators and linkers. Finally, the synthesized DOTA-TATE was successfully radiolabeled with [68Ga]Ga3+ (t1/2 = 68 min) with high radiochemical yields (30 min, 95 °C). We believe this work opens the door to the facile and low-cost synthesis of many new chelator-linker-peptide conjugates that were previously cumbersome or cost-prohibitive to produce with manual SPPS.

Artificial Neural Networks in Cardiovascular Diseases and its Potential for Clinical Application in Molecular Imaging.

In medical imaging, Artificial Intelligence is described as the ability of a system to properly interpret and learn from external data, acquiring knowledge to achieve specific goals and tasks through flexible adaptation. The number of possible applications of Artificial Intelligence is also huge in clinical medicine and cardiovascular diseases. To describe for the first time in literature, the main results of articles about Artificial Intelligence potential for clinical applications in molecular imaging techniques, and to describe its advancements in cardiovascular diseases assessed with nuclear medicine imaging modalities. A comprehensive search strategy was used based on SCOPUS and PubMed databases. From all studies published in English, we selected the most relevant articles that evaluated the technological insights of AI in nuclear cardiology applications. Artificial Intelligence may improve patient care in many different fields, from the semi-automatization of the medical work, through the technical aspect of image preparation, interpretation, the calculation of additional factors based on data obtained during scanning, to the prognostic prediction and risk-- group selection. Myocardial implementation of Artificial Intelligence algorithms in nuclear cardiology can improve and facilitate the diagnostic and predictive process, and global patient care. Building large databases containing clinical and image data is a first but essential step to create and train automated diagnostic/prognostic models able to help the clinicians to make unbiased and faster decisions for precision healthcare.

Dynamic Temperature Control System for the Optimized Production of Liquid Metal Nanoparticles

Nanoparticles (NPs) of gallium-based liquid metal (LM) alloys have potential applications in flexible electronics, drug delivery, and molecular imaging. They can be readily produced using top-down methods such as sonication. However, the sonication process generates heat that can cause dealloying of NPs through hydrolysis and oxidation of gallium. This limits the sonication power and period that can be applied for disrupting LM into smaller particles with high concentrations. Also, it remains challenging to achieve long-term colloidal stability of NPs in biological buffers. Here, we develop a dynamic temperature control system for improving the production performance of LM NPs. The enhanced performance is reflected by the significantly increased particle concentration, the decreased overall particle size, the prevention of the formation of oxide nanorods, and the versatility of producing NPs of different types of alloys. In addition, we design a brushed polyethylene glycol polymer with multiple phosphonic acid groups for effectively anchoring the NPs. More importantly, we discover that phosphate can effectively passivate the surface of NPs to further improve their stability. Using these strategies, the produced NPs remain stable in biological buffers for at least six months. Thus, the proposed methods can unleash the vast potential of LM NPs for biomedical applications.

Imaging the Extracellular Matrix in Prevalent Cardiovascular Diseases

The extracellular matrix (ECM) is a highly complex macromolecular network present in all tissues and organs. The ECM is continuously remodelling under an orchestrated process facilitated by many matrix-degrading and matrix-synthesising enzymes in both health and disease. Disturbance of this balance can be the result of or can lead to various diseases. In cardiovascular diseases (CVDs), changes to the ECM are evident in conditions including: atherosclerosis, myocardial infarction (MI), venous thromboembolism (VTE) and abdominal aortic aneurysm (AAA). ECM proteins and ECM regulating enzymes are differently expressed in various CVDs. Most importantly, the altered deposition, macromolecule arrangement and activity of the ECM makes it an attractive marker of disease onset, pathogenesis and progression. Many medical imaging modalities allow disease assessment by exploiting native image contrast, by using non-targeted or by using protein or cell specific (targeted) imaging probes. However, the ability to directly visualise and quantify changes in specific ECM proteins enhances our understanding of the biological role of these proteins, enables monitoring of disease progression and response to treatment and may improve patient diagnosis and allocation of personalised therapies. This review focuses on the biochemistry of the major extracellular matrix proteins and advancements in the development of ECM-targeted probes for molecular imaging of CVD, particularly for applications of molecular magnetic resonance imaging (MRI) and position emission tomography (PET) imaging.

Goos–Hänchen effect enabled optical differential operation and image edge detection

The Goos–Hänchen effect has found many important applications in photonics and optoelectronics since its discovery in 1947. Here, we propose unique applications of the Goos–Hänchen effect in optical differential operation and image edge detection. This Letter describes the theoretical foundation and experimental realization of the proposed scheme. By incorporating with the microscopy technique, our scheme may find important applications in cell and molecular imaging.

Functional Imaging of the Ocular Fundus Using an 8-Band Retinal Multispectral Imaging System

Application of functional imaging in ophthalmology requires efficient imaging techniques that can detect and quantify chromophores to visualise processes in vivo. The aim of the present study was to develop and evaluate a fast and affordable imaging system. We describe an eight-band retinal multispectral imaging (MSI) system and compare it with a hyperspectral imaging (HSI) device. Determination of blood oxygen saturation was studied as proof of principle. Reflectance of incident light is measured as 1/absorbance at different wavelengths between 440 nm and 580 nm. Both devices have incorporated optical bandpass filters in a mydriatic fundus camera. The MSI system scans the retina at eight pre-defined wavelengths specific for the spectrum of haemoglobin. The HSI system acquires a full scan from 480 to 720 nm in 5 nm steps. A simple assessment of the ratio between the absorbance peaks of oxygenated haemoglobin (HbO2) and reduced haemoglobin (HbR) was not suitable for generating validated oxygenation maps of the retina. However, a correction algorithm that compares the measured reflectance with reflectance spectra of fully oxygenated and fully deoxygenated blood allowed our MSI setup to estimate relative oxygen saturation at higher levels, but underestimated relative oxygen saturation at lower levels. The MSI device generated better quality images than the HSI device. It allows customisation with filter sets optimised for other chromophores of interest, and augmented with extrinsic contrast imaging agents, it has the potential for a wider range of ophthalmic molecular imaging applications.

Biogenesis of selenium nanoparticles and their anti-leukemia activity

Nanobiotechnology is an exuberant sphere of science that exhibits potential application in cancer therapy, targeted chemotherapy, molecular diagnosis and molecular imaging. Present investigation discloses green route synthesis of selenium nanoparticles leading to functionalization as anti leukemia nanomaterial. Emergence of resistance over cancer radiotherapy and chemotherapy is found to be the key factor behind the clinical treatment failure and recurrence. Selenium nanoparticles (SeNPs) with distinctive physicochemical features emerged as a novel nanocarrier and therapeutic agent with broad spectrum of medicinal properties. On the basis, biogenic technology has been proposed to synthesize selenium nanoparticles using Cassia auriculata and characterized using standard techniques. Newly synthesized selenium nanoparticles’ UV intense peak is achieved at 252 nm with crytalline surface morphology clear in SEM analysis. Cassia auriculata mediated selenium nanoparticles’ TEM analysis exhibits polydispersed with 10–20 nm. FTIR spectrum confirms the reduction of carboxyl group and capping of alkane group in Cassia auriculata synthesizes the selenium nanoparticles and its anti cancer potentiality has been explored by anti-leukemia activity using in vitro studies.

The effect of size range on ultrasound-induced translations in microbubble populations

Microbubble translations driven by ultrasound-induced radiation forces can be beneficial for applications in ultrasound molecular imaging and drug delivery. Here, the effect of size range in microbubble populations on their translations is investigated experimentally and theoretically. The displacements within five distinct size-isolated microbubble populations are driven by a standard ultrasound-imaging probe at frequencies ranging from 3 to 7 MHz, and measured using the multi-gate spectral Doppler approach. Peak microbubble displacements, reaching up to 10 μm per pulse, are found to describe transient phenomena from the resonant proportion of each bubble population. The overall trend of the statistical behavior of the bubble displacements, quantified by the total number of identified displacements, reveals significant differences between the bubble populations as a function of the transmission frequency. A good agreement is found between the experiments and theory that includes a model parameter fit, which is further supported by separate measurements of individual microbubbles to characterize the viscoelasticity of their stabilizing lipid shell. These findings may help to tune the microbubble size distribution and ultrasound transmission parameters to optimize the radiation-force translations. They also demonstrate a simple technique to characterize the microbubble shell viscosity, the fitted model parameter, from freely floating microbubble populations using a standard ultrasound-imaging probe.

Toward the Rational Design of Universal Dual Polarity Matrix for MALDI Mass Spectrometry.

A series of novel anthranilic acid derivatives I-IV, of which COOH-NH2 (I) and COOH-NHMe (IV) are endowed with acid and base bifunctionality, were designed and synthesized for matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry applications in dual polarity molecular imaging of biological samples, particularly for lipids. The heat of protonation, deprotonation, and proton transfer reaction as well as the capability of analyzing biomolecules in both positive and negative ion modes for I-IV were systematically investigated under standard 355 nm laser excitation. The results indicate correlation between dual polarity and acid-base property. Further, COOH-NHMe (IV) showed a unique performance and was successfully applied as the matrix for MALDI-TOF mass spectrometry imaging (MSI) for studying the mouse brain. Our results demonstrate the superiority of COOH-NHMe (IV) in detecting more lipid and protein species compared to commercially available matrices. Moreover, MALDI-TOF MSI results were obtained for lipid distributions, making COOH-NHMe (IV) a potential next generation universal matrix.

Synergistic cellular toxicity and uptake effects of iodixanol conjugated to anionic linear globular dendrimer G2

Objective(s): Early diagnosis of cancer using noninvasive imaging techniques has been discussed in several recent studies. The present study aimed to assess the synergistic effects of iodixanol-conjugated polyethylene glycol (PEG)-citrate (anionic linear globular) dendrimer G2 on MCF-7 breast cancer cells and human embryonic kidney 293 (HEK293) cells. Materials and Methods: PEG-citrate dendrimer G2 was synthesized and purified. The product was characterized using atomic force microscopy (AFM), electron energy loss spectroscopy (EELS), dynamic light scattering (DLS). At the next stage, the product was conjugated to iodixanol, purified and lyophilized. The cytotoxic effects of the iodixanol, plain PEG-citrate dendrimer G2, and iodixanol-PEG-citrate dendrimer G2 complex were evaluated using methylthiazole-tetrazolium (MTT) assay on the MCF-7 and HEK293 cells. Inductively coupled plasma mass spectrometry (ICP MS) is a mass spectrometry technique, which applies inductively coupled plasma to ionize samples.Results: According to the obtained results, the uptake of PEG-citrate dendrimer G2 iodixanol increased significantly compared to iodixanol alone (P<0.05), indicating the importance of lack of significant in-vitro toxicity. Moreover, in the particle size and higher negative zeta potential confirmed the loading of iodixanol in dendrimer G2. Increase, the loading of iodixanol in dendrimer was confirmed by the chemical shifts in HNMR. Conclusion: Therefore, it was concluded that the addition of anionic linear globular dendrimer G2 to iodixanol affected the cellular uptake of the drug with no significant toxicity. Recent findings also confirmed that this novel complex could be applied as an effective cancer imaging agent for molecular biology and molecular imaging applications.