Advance of Molecular Imaging Technology and Targeted Imaging Agent in Imaging and Therapy

Abstract

molecular imaging is an emerging battlefield that integrates advance imaging engineering with cellular and molecular biota. It can realize noninvasive and real time visual image, measurement of physiological or pathological march in the surviving organism at the cellular and molecular level, providing an effective method of information acquiring for diagnosis, therapy, and drug development and evaluating treatment of efficacy. molecular imaging requires high resolution and high sensitive instruments and specific imaging agents that link the imagination sign with molecular event. recently, the application of new emerging chemical technology and nanotechnology has stimulated the exploitation of imaging agents. Nanoparticles modified with minor molecule, peptide, antibody, and aptamer have been extensively applied for preclinical studies. remedy drug or gene is incorporated into nanoparticles to construct multifunctional image agents which allow for theranostic applications. In this review, we will discuss the characteristics of molecular imagination, the fresh imaging agent including targeted imagination agent and multifunctional imagination agentive role, adenine well as quote some examples of their application in molecular imagination and therapy .

1. Introduction

molecular imaging is a quickly developed multidiscipline which involves molecular biota, chemistry, calculator, engineering, and medicine [ 1 ]. It can realize noninvasive and actual time visual image, measurement of physiological or pathological process in the populate organism at the cellular or molecular level [ 2, 3 ]. And it besides allows repeated studies in the same animal, thus making it possible to collect longitudinal data and reduce the number of animals and price [ 4 ]. therefore, molecular visualize plays an important role in earlier signal detection, accurate diagnosis, and drug growth and discovery [ 5 – 7 ]. molecular imaging requires high gear resolution and high sensitive instruments to detect specific imaging agents that link the image signal with molecular consequence [ 8 ]. There are five imaging modalities available for molecular visualize, including x ray calculate imaging imaging ( CT ), ocular image ( OI ), radionuclide image ( involving PET and SPECT ), sonography ( US ) imaging and magnetic resonance image ( MRI ) [ 9 ]. In the past two decades, imaging instruments have grown exponentially. improvement in instruments and iterative persona reconstruction has resulted in high resolution images that reveal bantam wound and realize accurate quantification of biological process. A twin development has been the readiness of imaging agents which can bind their targets with high specificity and affinity [ 10 ]. In this review, we will discuss the characteristics of molecular imagination, some novel imaging agents based on nanoparticles including targeted imaging agent and multifunctional imagination agents, and cite some examples of their application in molecular imaging and therapy .

2. Molecular Imaging Technology

2.1. Radionuclide Imaging

Radionuclide molecular imaging including PET and SPECT is the earliest and most mature molecular imagination proficiency. due to its advantages of high sensitivity and quantifiability, radionuclide molecular imaging plays an crucial function in clinical and preclinical researches [ 11 ]. Over the past ten, with the progress of molecular biology and radiochemistry, a variety of tracer with gamey specificity and affinity appeared. A set of preclinical and clinical studies have confirmed the feasibility of using radionuclide molecular imagination to detect tumor and predict reply to therapy [ 12, 13 ].

2.1.1. PET

PET is the molecular imagination modality most extensively used in stream clinic everyday. It measures the signal originated from the radioactive decay of neutron-deficient radioisotopes ( such as 11C, 15O, 18F, and 131I ) that are intravenously injected into the body. These isotopes emit positrons which are ejected from the core as a result of springless interactions with electrons in surrounding tissue. The positrons quickly lose kinetic energy by spreading around the weave and collide with an electron to form two 511 keV photons which are taking trajectory 180° apart, and this is an event known as annihilation [ 14 ]. A PET detector surrounding the subject is designed to detect the signal and convert the result electrical signal into sinograms that are last rebuilt into tomographic images. Because of its high sensitivity of 10−1110−12 mol/L, unlimited depth of penetration, and quantitative capabilities, PET becomes a brawny tool for clinical diagnosis and basic research including neurology, cardiology, and particularly oncology [ 15, 16 ]. In the clinic, PET is all-important for cancer detection and staging, ampere well as evaluation of response to therapy. A mass of radiotracer has been employed for cancer visualize, with 18F-FDG being the identify one. The chief disadvantage of PET is the miss of anatomical reference parameters to identify molecular events with accurate correlation coefficient to anatomic findings, and this disadvantage has recently been compensated by merging these devices with either CT or MRI [ 17 ]. It is reported that whole-body PET/CT improves the accuracy of cancer diagnosis and spy. With the widespread of instrument, PET/CT has become an authoritative creature for predicting remedy response, providing useful information for the decision to stop ineffective discussion or switch to a more efficient treatment. It is shown that up to 40 % of patients with cancer have changed the treatment because of application of PET/CT [ 18 ]. recently, Andrade et alabama. [ 19 ] evaluated 40 patients with invasive ductal breast carcinoma that received neoadjuvant chemotherapy by FDG-PET/CT. They found that the application of FDG-PET/CT after the second course of NAC could predict curative response in ductal breast carcinoma and potentially recognise the nonresponding patients for whom ineffective chemotherapy should be avoided. early limitations of PET are their safety profile and the prerequisite of cyclotron to produce radiopharmaceuticals .

2.1.2. SPECT

Unlike PET, SPECT directly detects gamma-ray photon emitted by the chosen radionuclide during their decay. Compared with PET, SPECT is more low-cost and extensively employed in the clinical routine, but it is generally less sensible since the photons which are not traveling along the axis of the collimator are rejected by the scanner. The spatial resolution ( 8–10 millimeter ) of SPECT is lower than that of clinical PET ( 5–7 millimeter ) [ 20 ], but the spatial settlement of small animal SPECT ( micro-SPECT ) is higher than that of PET due to the development of imaging equipment. therefore micro-SPECT is more available in preclinical investigations including the transformation research and animal studies such as oncology, neurology, cardiovascular disease, and drug growth [ 21, 22 ]. additionally, since the radionuclides normally available for SPECT have longer half life periods ( ranging from a few hours to days ), longitudinal studies can be performed. Based on the isotope-specific energies of the utter photons ( for example, [ 111In ] indium : 171 and 245 keV ; [ 177Lu ] lutetium : 202 and 307 keV ), SPECT can distinguish unlike radioisotopes, consequently making it possible to image unlike targets simultaneously. Hijnen et alabama. [ 23 ] took advantage of this characteristic and devised a dual-isotope experime
nt on a micro-SPECT system. In their analyze, they quantified the biodistribution and tumor uptake of the angiogenesis tracer cRGD via SPECT ( Figure 1 ). however, dual-tracer images can be badly deformed due to cross spill the beans between the two isotopes. recently, Hapdey et alabama. [ 24 ] put advancing a generalized spectral factor analysis ( GSFA ) method for solving this problem in coincident /123I SPECT, which proved that coincident /123I imaging can provide images of exchangeable quantitative accuracy through GSFA as when using consecutive and scatter-free/123I imaging in mind SPECT .

2.2. Magnetic Resonance Imaging

magnetic rapport imaging ( MRI ) is a highly versatile imaging mood [ 25 ]. During the past decades, improvement in instrument launched the field of MRI into a raw era of molecular imagination. The merits of MRI as an visualize modality for molecular image are relatively high temporal role and spatial resolution, excellent tissue contrast and weave penetration, no ionize radiotherapy, noninvasiveness for serial studies, and coincident acquisition of anatomic social organization and physiologic affair [ 26 ]. Nevertheless, molecular MRI is limited by its relatively first gear sensitivity, and this requires the introduction of imaging agent and exploitation of brawny signal amplification strategies. Imaging agent blueprint is therefore an important topic in molecular MRI. Currently, the MR imaging agents are chiefly divided into two kinds : ferromagnetism contrast agents and paramagnetic contrast agents. The former is considered as negative line agents which chiefly reduce the signal in T2-weighted images, while the latter is referred to as positive contrast agents that increase the sign in T1-weighted images. The most spokesperson negative contrast agents are superparamagnetic iron oxide ( SPIO ) and ultrasmall superparamagnetic iron oxide ( USPIO ), and typical positive contrast agents are modest molecular weight compounds involving a single Lanthanide chelate as signal producing chemical element ( for example, gadolinium-DTPA ). To date, there are numerous examples of MR molecular imaging which have confirmed the potential of this technology. Rapley et aluminum. [ 27 ] demonstrated that the application of antibody-SPIO complex and MRI was a feasible method acting for detecting and measuring nucleosome assiduity in vitro, which was expected to become a diagnostic, predictive, and predictive tool in the management of cancer. recently, Debergh et alabama. [ 28 ] showed that the application of a minor monogadolinated tracer targeting integrin and MR molecular visualize was a promise strategy for evaluation of colorectal cancers associated angiogenesis .

2.3. X-Ray Computed Tomography Imaging

CT imaging technologies have undergone a very fast development in the last years. gamey resoluteness little animal CT ( micro-CT ) has transformed CT imaging from organ, tissue to molecular level, which is playing an increasingly significant function in preclinical researches [ 29, 30 ]. The independent advantages of CT are high spatial resoluteness ( micro-CT is 0.020.30 millimeter ; clinical CT is 0.52.0 millimeter ), fast skill time, relative simplicity, handiness, excellent hard-tissue visualize. Due to limitations like ionizing radiation, limited soft tissue resolution, and hapless sensitivity ( 10−210−3 mol/L ), CT is always combined with other imaging modalities such as SPECT, PET to provide anatomic parameters for the biochemical and physiologic findings [ 31 ]. recently, the development of CT contrast agents has brought newfangled hope for CT molecular image [ 32 ]. For model, Hyafil et aluminum. [ 33 ] reported cellular imaging of macrophage in the atherosclerotic brass in a rabbit model through CT with iodinate nanoparticles ( N1177 ) ( Figure 2 ). Pan et aluminum. [ 34 ] found that polymeric nanoparticles contrast agents which were comprised of organometallics or radiopaque organically soluble elements could further improve the imagination sensitivity for CT. besides, targeted aureate nanoparticles for CT imaging at the cellular and molecular tied have been successfully prepared. Li et aluminum. [ 35 ] conjugated 2-deoxy-D-glucose ( 2-DG ) to a gold nanoparticle to prepare CT molecular visualize agent ( AuNP-2-DG ) which could be used for CT imaging to obtain high resolution anatomic structure and metabolic information of tumor. The results of in vitro experiments proved that AuNP-2-DG could be used as a functional CT contrast agent. however, though the findings from these CT molecular imaging experiments show attractive prognosis, further study is required to explore the feasibility of CT molecular visualize .(a)
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2.4. Optical Imaging

optical molecular imaging engineering is an emerging engineering, based on genomics, proteomics, and mod ocular engineering. At confront, the most widely used ocular molecular imaging modalities in vivo include bioluminescence visualize ( BLI ) and fluorescence imaging. As optical imagination is performed through the practice of light, thus it is considered as relatively safe. And due to their advantages of high sensitivity and depleted monetary value, optical imaging plays a central function in the investigation of tumor happening, progressions and relevant drug growth [ 36, 37 ]. The main disadvantages of ocular imaging are that the astuteness of penetration is limited as the energy of photons is low, thereby making it about impossible to image deep tissues in large subjects. Due to the small size of experimental animals, the depth of penetration is not a trouble for them. consequently, ocular imaging is widely used for preclinical research. BLI is taking advantage of the inner light produced by the enzymatic oxidation reaction of luciferase and its substrate. The luciferase is normally generated from the reporter gene. As opposed to fluorescence imaging, the light source of BLI is from inner. And since weave do not produce endogenous bioluminescence, the sensitivity and bespeak to setting is better than fluorescence imaging. BLI is wide used to observe the biological processes in vivo like disease progress, certain gene formulation, tumor growth, and metastasis and evaluate the consequence of certain treatments. For example, Niu et alabama. [ 38 ] introduced a caspase-3 specific cyclic firefly luciferase reporter gene ( pcFluc-DEVD ) into UM-SCC-22B and 4T1 cells then induced apoptosis of the cells by unlike concentrations of doxorubicin and evaluated the effect by BLI. The results exhibited that BLI volume was increased a early as 24 henry after treatment and achieved a maximal at around day 12, which indicated that BLI with pcFluc-DEVD as a reporter gene can help to observe the kinetics of the apoptotic process in a real-time manner ( Figure 3 ) .
fluorescence image is a versatile proficiency with a number of strengths such as relative low cost and multiplexed imaging. As abstemious is absorbed by hemoglobin and other molecules, the depth of penetration is limited ( normally < 1 centimeter ). Hence, fluorescence image is chiefly used in animal researches. Atreya et aluminum. [ 39 ] took adva ntage of the sport that integrin and vascular endothelial growth factor receptor ( VEGFR ) are overexpressed in tumor ; they used the integrin fluorescent probe to detect the tumor angiogenesis in bare shiner. The consequence showed there were strong fluorescence signals for in vivo via a fluorescent scanner, which indicated angiogenesis increased in the cancer tissue. besides, they proved that the target visual image of VEGF could be achieved via a fluorescent-labeled antibody against the VEGFR ( Figure 4 ) .(a)
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2.5. Ultrasound Molecular Imaging

With the use of sonography contrast agent, ultrasound imaging enables specific and medium depiction of molecular targets [ 40, 41 ]. Compared with other molecular imaging modalities, ultrasound molecular imaging has many advantages including good temporal resolution, quantitative data, real-time commit, noninvasiveness, relatively cheap cost, and no ionize radiation. In summation, it is a singular mood in some sense that it can be employed for diagnostic visualize and as a remedy creature [ 42, 43 ]. Mancini et aluminum. [ 44 ] proved that the use of ultrasound molecular imagination with microbubble targeting VEGFR-2 might be a valuable method acting for noninvasively detecting and quantifying of VEGFR-2 expression in thyroid gland cancer in mouse, and it is besides a utilitarian instrument for differentiating benign from malignant thyroid nodules. Besides, for diagnostic purposes, molecular ultrasound imaging can besides be applied for theranostic purposes. This is chiefly achieved by loading gene or drug onto microbubble. The interaction between sonography and microbubble results in stable and inertial cavitation, which can transiently increase vascular and cellular membrane permeability, thereby potentially augments the eruption and/or take up of drugs or genes loaded on microbubble. Li et alabama. [ 45 ] prepared a novel microbubble carrying 10-HCPT, and they demonstrated that the injection of 10-HCPT loaded microbubble and exposure to ultrasound could increase the drug concentration in tumor signally, leading to a significant increase in tumor inhibition rate ( 70.6 % ) compared with 10-HCPT loaded microbubble alone ( 47.8 % ) deoxyadenosine monophosphate well as commercial HCPT injection ( 49.4 % ). Our studies have confirmed that the combination of sonography and microbubble could significantly increase the transfection efficacy [ 46 ] .

2.6. Multimodality Imaging

Among all molecular image techniques, every molecular image proficiency has its advantages and disadvantages. No unmarried one is perfect and adequate to provide comprehensive examination information for disease diagnosis [ 47 ]. In general, CT, MRI, and US are anatomic imaging methods but they have gloomy sensitivity. Radionuclide image and optical imagination are functional imaging techniques, while they suffer from gloomy solution, which frequently lack structural parameter. The combination of different molecular imagination techniques, namely, multimodality image, can provide synergetic advantages over any modality entirely and compensate for the disadvantages of each imaging organization while taking advantage of their person strengths, which has become the developmental tendency of modern medical image immediately [ 48 – 51 ]. Multimodality imaging such as PET/SPECT, PET/CT, and PET/MRI can be used to obtain anatomical reference and molecular data while providing adequate data for clinical diagnosis [ 52 ]. For exercise, the combination of PET and CT can produce coregistered data providing regions of increase 18F-FDG collection on the PET trope with accurate correlation to anatomic findings ’ locations on the CT scan, thus the specificity and sensitivity of PET in detecting lesion are enhanced, therefore as the accuracy in delineating target volume. Abgral et aluminum. [ 53 ] conducted a report that included 91 patients who once had HN cancer but were cured and without any clinical evidence of recurrence to assess the diagnostic capabilities of 18F-FDG PET/CT in these patients. The results showed that the sensitivity, specificity, and accuracy of 18F-FDG PET/CT for the diagnosis of HN cancer recurrence were 100 %, 85 %, and 90 %, respectively. The positive predictive prize was 77 %, while the damaging predictive measure was 100 %.

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magnetic resonance imaging shows obvious advantages over CT including excellent soft tissue line, high gear spatial resolving power, and no ionize radiation sickness ; frankincense studies of PET/MRI become the focus of concern and have achieved initial progress. Lee et aluminum. [ 54 ] used PET/MRI to evaluate the presence of monocytes in nonischemic distant partition after myocardial infarct, which proved that incendiary cells of infarct zone and distant noninfarcted area could be observed by PET/MRI images. recently, PET/MRI has been applied to clinic. Kjær et alabama. [ 55 ] performed a PET/MRI interrogation on a female patient with cervical cancer for restaging following radiotherapy and compared the results with PET/CT, which showed that PET/MRI performed well compared to PET/CT. It had a more precise definition of the elementary tumor ( Figure 5 ). however, PET with MRI in a single gantry which is dedicated to coincident PET/MRI is technically more challenge .
In accession to the combination of PET and CT or MRI, other multimodality imaging methods have been reported, such as OI/US, OI/CT, OI/MRI, and US/MRI [ 56 – 58 ]. OI is a versatile technique in preclinical research as it possesses the advantages of gamey specificity and sensitivity, low cost, relatively high-flux, and appliance. Ultrasound, on the other hand, has persuasiveness of high resolving power. The strengths of these imaging techniques are complemental. The combination of them, which takes advantage of high sensitivity of ocular imaging and high resolution of sonography, may produce synergistic effect and provide images with full spatial and temporal resolving power. recently, Li et aluminum. [ 56 ] designed a organization which integrated 3D ultrasound image and 3D continuous transillumination fluorescence imaging. They evaluated the feasibility and performance of the system by using phantoms and atherosclerosis disease sneak model. Results proved that sonography morphologic images could improve the quality of the fluorescent picture reconstruction and the action of VCAM could be detected through the arrangement, which showed a great likely for the application in in vivo molecular visualize. As this organization could provide geomorphologic information while keeping the merits of low cost of fluorescence imaging, it is worthy of forwarding and application for the future. consequently, it can be seen that multimodality imagination is not a childlike accession of assorted imaging technologies but preferably for producing synergistic effect. It can provide more information to understand the biological processes comprehensively and objectively. But it is still unmanageable to carry out multimodality imaging due to existing problems regarding the accuracy of coregistered visualize, supernumerary ionize radiation, the supernumerary dose of contrast agent, and the perniciousness of fuse contrast agents. therefore, it is in pressing need of developing multimodality molecular imaging agentive role .

3. Imaging Agents

molecular
imaging depends greatly on the development of particular and sensitive imaging agents, which is a pivotal rate-limiting tone in the development of molecular imaging [ 8 ]. In a molecular imaging study, imaging agents are chiefly used for interrogating or coupling back about a specific target of interest [ 10 ]. They normally consist of signal component and targeting part. In recent years, the promotion of biochemistry has been achieved and the development of molecular image technologies has led to the output of a mass of molecular imaging agents [ 57 ]. A aggregate of targeting moieties, such as modest molecule, peptide, antibody, and aptamer, is applied to decorate ligand-directed ( “ targeted ” ) imaging agents to recognise specific pathological tissues [ 9 ]. Furthermore, nanoparticles with singular properties have emerged as a bright class of molecule imaging agents. Targeting moieties, curative drug or gene, and different imaging labels can be incorporated into nanoparticles to construct target imagination agents and multifunctional imagination agents which allow for multimodal imaging and theranostic applications [ 58, 59 ] .

3.1. Targeted Molecular Imaging Agents Based on Small Molecules

small molecules, of which the size is normally less than 500 Da, are playing an crucial character in molecular image. Due to their little size, little molecules have a wide range of application including intracellular and central nervous organization. 18F-FDG is the most widely used imaging agent based on small molecules, which is clinically applied for cancer imaging [ 60 ]. Ren et alabama. [ 61 ] reported the use of gadolinium ( Gd ) to label uniformly phosphorothioate-modified human tumor telomerase inverse transcriptase ( hTERT ) antisense oligonucleotide ( ASON ) targeting hTERT messenger rna and conducted a discipline in BALB/c nude mouse with 7.0T Micro-MRI, showing that Gd-DOTA-ASON was a likely intracellular MR contrast probe for signal detection of telomerase-positive carcinoma ( Figure 6 ) .

3.2. Targeted Molecular Imaging Agents Based on Peptide

Peptide is an crucial class of ligand used for molecular imagination [ 62 ]. Compared to little molecules, peptide has many advantages, such as superior selectivity and specificity and easier modification without changing their adhere properties or distribution. additionally, peptide is more stable in atmospheric temperature than antibodies and has a lower immunogenicity compared with antibodies. recently, Hansen et aluminum. [ 63 ] conjugated a peptide which could bind to the plasminogen activator plasminogen activator receptor ( uPAR ) with high specificity and affinity to polyethylene ethylene glycol ( PEG ) coated USPIO nanoparticles. In vitro consequence showed that the peptide conjugated USPIO nanoparticles had a five times higher uptake in a uPAR positive cell line compared to the nanoparticles with a nonspecific peptide. Hackel et alabama. [ 64 ] used 18F labelled 2 cystine slub peptides and performed micro-PET on BxPC3 pancreatic adenocarcinoma xenografts in mouse with them. Results indicated that these cystine ravel peptide tracers had senior high school tumor uptake, showing translational promise for cancer imaging .

3.3. Targeted Molecular Imaging Agents Based on Antibodies

Characterized by the ability to bind their target with high specificity and affinity and easy synthesis, antibodies have been applied for diagnosis and therapy [ 65 ]. so far, there are more than eight FDA-approved radiolabeled antibodies approved for SPECT molecular image and about twenty antibodies approved for therapy. recently, Zhang et aluminum. [ 66 ] reported the use of PET with ( 61/64 ) Cu-NOTA-TRC105-Fab to visualize CD105 expression, which showed obvious and target-specific consumption in the 4T1 tumor ( Figure 7 ). Abdolahi et alabama. [ 67 ] conjugated superparamagnetic iron oxide nanoparticles with an antibody which could bind to the extracellular domain of PSMA and performed MRI with it. Results demonstrated that the nanoprobe could act as a specific MRI line agent for detection of PSMA-expressing prostate gland cancer cells .

3.4. Targeted Molecular Imaging Agents Based on Aptamer

Aptamer, single-stranded deoxyribonucleic acid or RNA oligonucleotides, can bind to their prey with high gear selectivity and specificity [ 68 ]. Because they enjoy a number of merits including high affinity and specificity, depleted immunogenicity, small size, stable structures, and ease of output, aptamers have recently attracted increasing attention [ 69, 70 ]. In holocene years, probe based on aptamer provides a new strategy for molecular imaging. Shi et aluminum. [ 71 ] reported the use of an activatable aptamer probe ( AAP ) which could bind membrane proteins of populate cancer cells with a high academic degree of specificity to visualize the cancer inside mouse. The results showed that the AAP could be used to specifically, quickly detect CCRF-CEM cell in the serum or CCRF-CEM cell tumor in mouse. Bagalkot et alabama. [ 72 ] recently described the manipulation of a novel quantum acid conjugated with prostate specific membrane antigen ( PSMA ) RNA aptamers to image and cure cancer. Aptamer conjugated nanoparticles provide newly scheme for targeted multimodality imaging. Hwang et aluminum. [ 73 ] described a multimodal cancer-targeted image system for coincident fluorescence imaging, radionuclide visualize, and MRI in vivo through an aptamer conjugated nanoparticle probes. The probe was synthesized by the AS1411 aptamer ( MF-AS1411 ) which targeted nucleolin a cobalt-ferrite nanoparticle comprised core of fluorescent rhodamine and a silica-based blast. then the probe was injected intravenously into nude mice bearing tumor xenografts and performed 67Ga radionuclide visualize and MRI. The SPECT double showed that this probe exhibited a better accumulation in tumor 24 heat content after injection than the control group. furthermore, MRI images showed the AS1411 conjugated nanoparticle as black signal in tumours 24 h after injection, while there were no T2 negative signals in the manipulate group. last, fluorescence images exhibited a higher signal in tumor of mice injected with aptamer conjugated nanoparticles compared to the control one. Taken together, these results proved that aptamers can deliver the nanoparticles to tumor tissue ( Figure 8 ) .

3.5. Multifunctional Molecular Imaging Agent

With multimodality imaging techniques intelligibly on the rise, the development over these newfangled techniques has led to explosive growth in multimodal imaging agent researches [ 74, 75 ]. Since different imaging techniques can only detect their comparable line agents, the patient who intends to perform multimodality imagination may need to inject different contrast mediums. This will increase the affected role ’ south economic effect and the extra stress on the blood clearance mechanism. furthermore, it will expose him to side effect by the reciprocal noise between different contrast agents. Therefore, many researches are trying to design and develop a probe which can be detected by unlike imaging modalities so as to boost the clinical benefits of multimodality visualize. Due to their limited attachment points, little molecules are not desirable for multimodality imaging. On line, nanoparticles are attractive candidates for multimodal imaging probe [ 76 – 78 ]. They possess high surface areas to book ratio, which allows multiple modifications to ligands and different imagination agents within the nanoparticles or on its coat. recently, John et alabama. [ 77 ] described
the use of a target multimodal protein-shell microsphere which contained iron oxide nanoparticles in their cores and conjugated with the RGD peptide ligand to enhance the imaging ability of ultrasound, MRI and MM-OCT. besides, Liu et alabama. [ 79 ] designed an iron oxide nanoparticle-embedded polymeric microbubble used for ultrasound visualize and MRI. Liang et aluminum. [ 80 ] reported the synthesis and evaluation of streptavidin nanoparticle-based complexes which were functionalized with biotinylated anti-Her2 Herceptin antibody as multimodality imaging agents to detect tumor in a model via both SPECT system and IVSI fluorescence camera. Willmann et aluminum. [ 81 ] prepared a polymeric contrast agentive role MBQDs – PLGA suited for ocular and supersonic molecular imagination. In addition, they used PET to assess in vivo whole-body biodistribution of microbubbles functionalized with anti-VEGFR2 antibodies that were marked by the radiofluorination agent N-succinimidyl-4- [ 18F ] fluorobenzoate ( SFB ) [ 82 ]. Hence, it can be seen that multimodal image agents are available, but their clinical lotion distillery need far research. aside from imaging agentive role and ligands, therapeutic drug or gene can besides be incorporated in nanoparticles to construct theragnostic agentive role which have an important character in therapy. This agent enables notice of the extent of disease anterior to therapeutic intervention. The ability to identify disease condition and controlled rescue of drug using the same agentive role would help ensure that only likely reactive patients would be treated. consequently, theragnostic agents show a promise prospective in therapy. Yan et aluminum. [ 83 ] have synthesized a fresh targeted drug-loaded microbubble functionalized with LyP-1, a breast tumor homing peptide, and evaluated its effect in vivo. Results of the cogitation demonstrated that the LyP-1-coated PTX-loaded microbubble improved the anticancer efficacy markedly and had great likely in ultrasound-assisted breast cancer treatment .

4. Prospect

molecular imaging technology rightfully enables dynamic, quantitative visual image of specific biochemical activity without injury in vivo at cellular and molecular degree. It has a directly impact on the modern and future music. In late years, molecular imaging technology has seen certain progresses in the early diagnosis, remedy effect monitor of diseases, drug development, gene therapy, and other fields, but some winder problems regarding theory, technology, and system, particularly molecular imaging agents and imaging equipment, are not solved so far. The exploitation of a new probe is not straightforward. due to barriers in delivery, biological compatibility, and the diversity between species, there are only a few of clinical molecular imagination agents available presently. With the development of engineering, it is expected that more promotion will be achieved in the sphere of molecular image agent including targeted molecular visualize agentive role and multifunctional molecular image agents. The application of nanoparticles has provided a chopine for theranostic researches. additionally, although a number of molecular imaging instruments are available, all have their limitations. For exemplify, MRI is a useful clinical diagnostic cock, but it suffers from slightly poor sensitivity. consequently, more focus should be performed on polish and improving upon existing orchestration and further efforts geared toward the combination of different modalities so as to make up the disadvantages of different instruments. Multimodality imaging has many advantages, but some problems however exist and need to be solved, such as the difficulty of designing a PET/MRI organization suited for the entire consistency, monetary value increase, performance improvement, and multimodal contrast agentive role coalition. furthermore, as an emerging interdisciplinary science which brings together nuclear medicine, supersonic medicate, radioscopy, drugstore, and materials science, the development of molecular imaging needs to strengthen interdisciplinary cooperation. Awareness of importance of multidisciplinary joint inquiry should be strengthened.

The rapid expansion of molecular imaging application shows a promise prognosis. Although overall the molecular imagination is still at the initial stagecoach of development, we believe that within the support and cooperation from imaging experts and scholars, molecular visualize techniques would finally realize clinical transformation .

Conflict of Interests

The authors declare no conflict of interests regarding the issue of this wallpaper .

Acknowledgments

This oeuvre was supported by National Natural Science Foundation of China ( no. 81371572 ), Research Fund of Doctoral Program of Universities ( no. 20124401120002 ), Sixth Special Project of China Postdoctoral Science Foundation ( no. 2013T60826 ), China Postdoctoral Science Foundation ( no. 2011M501375 ), Research Project of Guangzhou Technology Bureau ( no. 12C22021645 ), Research Project of Science and Technology Guangdong Province ( no. 2012B050300026 ), Research Project of Science and Technology Liwan District ( no. 20124414124 ), and Natural Science Foundation of Guangdong Province ( no. S2012040006593 ) .

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