Role of molecular imaging in prognosis,diagnosis,and treatment of gastrointestinal cancers:An update on new therapeutic methods

One of the leading causes of cancer-related death is gastrointestinal cancer,which has a significant morbidity and mortality rate.Although preoperative risk assessment is essential for directing patient care,its biological behavior cannot be accurately predicted by conventional imaging investigations.Potential pathophysiological information in anatomical imaging that cannot be visually identified can now be converted into high-dimensional quantitative image features thanks to the developing discipline of molecular imaging.In order to enable molecular tissue profile in vivo,molecular imaging has most recently been utilized to phenotype the expression of single receptors and targets of biological therapy.It is expected that molecular imaging will become increasingly important in the near future,driven by the expanding range of biological therapies for cancer.With this live molecular fingerprinting,molecular imaging can be utilized to drive expression-tailored customized therapy.The technical aspects of molecular imaging are first briefly discussed in this review,followed by an examination of the most recent research on the diagnosis,prognosis,and potential future clinical methods of molecular imaging for GI tract malignancies.

Advancements of molecular imaging and radiomics in pancreatic carcinoma

Despite the recent progress of medical technology in the diagnosis and treatment of tumors,pancreatic carcinoma remains one of the most malignant tumors,with extremely poor prognosis partly due to the difficulty in early and accurate imaging evaluation.This paper focuses on the research progress of magnetic resonance imaging,nuclear medicine molecular imaging and radiomics in the diagnosis of pancreatic carcinoma.We also briefly described the achievements of our team in this field,to facilitate future research and explore new technologies to optimize diagnosis of pancreatic carcinoma.

Optical Molecular Imaging Frontiers in Oncology: The Pursuit of Accuracy and Sensitivity

Cutting-edge technologies in optical molecular imaging have ushered in new frontiers in cancer research, clinical translation, and medical practice, as evidenced by recent advances in optical multimodality imaging, Cerenkov luminescence imaging(CLI), and optical imageguided surgeries. New abilities allow in vivo cancer imaging with sensitivity and accuracy that are unprecedented in conventional imaging approaches. The visualization of cellular and molecular behaviors and events within tumors in living subjects is improving our deeper understanding of tumors at a systems level. These advances are being rapidly used to acquire tumor-to-tumor molecular heterogeneity, both dynamically and quantitatively, as well as to achieve more effective therapeutic interventions with the assistance of real-time imaging. In the era of molecular imaging, optical technologies hold great promise to facilitate the development of highly sensitive cancer diagnoses as well as personalized patient treatment—one of the ultimate goals of precision medicine.

Diffusion magnetic resonance imaging: A molecular imaging tool caught between hope, hype and the real world of “personalized oncology”

"Personalized oncology" is a multi-disciplinary science, which requires inputs from various streams for optimal patient management. Humongous progress in the treatment modalities available and the increasing need to provide functional information in addition to the morphological data; has led to leaping progress in the field of imaging. Magnetic resonance imaging has undergone tremendous progress with various newer MR techniques providing vital functional information and is becoming the cornerstone of "radiomics/radiogenomics". Diffusionweighted imaging is one such technique which capitalizes on the tendency of water protons to diffuse randomly in a given system. This technique has revolutionized oncological imaging, by giving vital qualitative and quantitative information regarding tumor biology which helps in detection, characterization and post treatment surveillance of the lesions and challenging the notion that "one size fits all". It has been applied at various sites with different clinical experience. We hereby present a brief review of this novel functional imaging tool, with its application in "personalized oncology".

Tumor Molecular Imaging with Nanoparticles

Molecular imaging(MI)can provide not only structural images using traditional imaging techniques but also functional and molecular information using many newly emerging imaging techniques.Over the past decade,the utilization of nanotechnology in MI has exhibited many significant advantages and provided new opportunities for the imaging of living subjects.It is expected that multimodality nanoparticles(NPs)can lead to precise assessment of tumor biology and the tumor microenvironment.This review addresses topics related to engineered NPs and summarizes the recent applications of these nanoconstructs in cancer optical imaging,ultrasound,photoacoustic imaging,magnetic resonance imaging(MRI),and radionuclide imaging.Key challenges involved in the translation of NPs to the clinic are discussed.

Recent progress in the molecular imaging of therapeutic monoclonal antibodies

Therapeutic monoclonal antibodies have become one of the central components of the healthcare system and continuous efforts are made to bring innovative antibody therapeutics to patients in need.It is equally critical to acquire sufficient knowledge of their molecular structure and biological functions to ensure the efficacy and safety by incorporating new detection approaches since new challenges like individual differences and resistance are presented.Conventional techniques for determining antibody disposition including plasma drug concentration measurements using LC-MS or ELISA,and tissue distribution using immunohistochemistry and immunofluorescence are now complemented with molecular imaging modalities like positron emission tomography and near-infrared fluorescence imaging to obtain more dynamic information,while methods for characterization of antibody’s interaction with the target antigen as well as visualization of its cellular and intercellular behavior are still under development.Recent progress in detecting therapeutic antibodies,in particular,the development of methods suitable for illustrating the molecular dynamics,is described here.

Preclinical and clinical applications of specific molecular imaging for HER2-positive breast cancer

Precision medicine and personalized therapy are receiving increased attention, and molecular-subtype classification has become crucial in planning therapeutic schedules in clinical practice for patients with breast cancer. Human epidermal growth factor receptor 2(HER2) is associated with high-grade breast tumors, high rates of lymph-node involvement, high risk of recurrence, and high resistance to general chemotherapy. Analysis of HER2 expression is highly important for doctors to identify patients who can benefit from trastuzumab therapy and monitor the response and efficacy of treatment. In recent years, significant efforts have been devoted to achieving specific and noninvasive HER2-positive breast cancer imaging in vivo. In this work, we reviewed existing literature on HER2 imaging in the past decade and summarized the studies from different points of view, such as imaging modalities and HER2-specific probes. We aimed to improve the understanding on the translational process in molecular imaging for HER2 breast cancer.

Noninvasive in vivo cell tracking using molecular imaging:A useful tool for developing mesenchymal stem cell-based cancer treatment

Mounting evidence has emphasized the potential of cell therapies in treating various diseases by restoring damaged tissues or replacing defective cells in the body.Cell therapies have become a strong therapeutic modality by applying noninvasive in vivo molecular imaging for examining complex cellular processes,understanding pathophysiological mechanisms of diseases,and evaluating the kinetics/dynamics of cell therapies.In particular,mesenchymal stem cells(MSCs)have shown promise in recent years as drug carriers for cancer treatment.They can also be labeled with different probes and tracked in vivo to assess the in vivo effect of administered cells,and to optimize therapy.The exact role of MSCs in oncologic diseases is not clear as MSCs have been shown to be involved in tumor progression and inhibition,and the exact interactions between MSCs and specific cancer microenvironments are not clear.In this review,a multitude of labeling approaches,imaging modalities,and the merits/demerits of each strategy are outlined.In addition,specific examples of the use of MSCs and in vivo imaging in cancer therapy are provided.Finally,present limitations and future outlooks in terms of the translation of different imaging approaches in clinics are discussed.

Construction and Identification of the Adenoviral Vector with Dual Reporter Gene for Multimodality Molecular Imaging

Summary： In this study, the recombinant adenovirus （Ad） vector containing dual reporter gene [i.e. human transferrin receptor gene （TFRC） and firefly luciferase reporter gene] was constructed to provide a novel experimental tool for magnetic resonance （MR） and bioluminescence dual-modality molecular imaging. The cDNA of TFRC was amplified by polymerase chain reaction （PCR） and cloned into the multiple cloning site of pShuttle-CMV-CMV-Luciferase vector. After identification by Sfi I digestion and sequencing, pShuttle-TFRC-Luciferase vector and the adenoviral backbone vector （pAdeno） were subjected to homologous recombination. The correct recombinant plasmid was then transfected into 293 packaging cells to produce adenoviral particles and confirmed by PCR. After infection of human colo- rectal cancer LOVO cells with Ad-TFRC-Luciferase, the expressions of transferrin receptor （TfR） and luciferase protein were detected respectively by Western blotting and bioluminescence imaging in vitro. The results showed that TFRC gene was successfully inserted into the adenoviral shuttle vector carrying luciferase gene. DNA sequence analysis indicated that the TFRC gene sequence in the shuttle plasmid was exactly the same as that reported in GenBank. The recombinant plasmid was identified correct by restriction digestion. Ad-TFRC-Luciferase recombinant adenovirns was constructed successfully, and the virus titer was 1.6x10^10 pfu/mL. Forty-eight h after dual reporter gene transfection, the expressions of TfR and luciferase protein were increased significantly （P〈0.01）. It was concluded that the recombinant adenovirus vector with dual reporter gene was successfully established, which may be used for in vivo tracing target cells in multimodality imaging.

DEVELOPMENT OF NEEDLE-BASED MICROENDOSCOPY FOR FLUORESCENCE MOLECULAR IMAGING OF BREAST TUMOR MODELS

Fluorescence molecular imaging enables the visualization of basic molecular processes such as gene expression,enzyme activity,and disease-specific molecular interactions in vivo using targeted contrast agents,and therefore,is being developed for early detection and in situ characterization of breast cancers.Recent advances in developing near-infrared fluorescent imaging contrast agents have enabled the specific labeling of human breast cancer cells in mouse model systems.In synergy with contrast agent development,this paper describes a needle-based fluorescence molecular imaging device that has the strong potential to be translated into clinical breast biopsy procedures.This microendoscopy probe is based on a gradient-index(GRIN)lens interfaced with a laser scanning microscope.Specifications of the imaging performance,including the field-of-view,transverse resolution,and focus tracking characteristics were calibrated.Orthotopic MDA-MB-231 breast cancer xenografts stably expressing the tdTomato red fluorescent protein(RFP)were used to detect the tumor cells in this tumor model as a proof of principle study.With further development,this technology,in conjunction with the development of clinically applicable,injectable fluorescent molecular imaging agents,promises to perform fluorescence molecular imaging of breast cancers in vivo for breast biopsy guidance.

Role of molecular imaging in the management of patients affected by inflammatory bowel disease:State-of-the-art

AIM To present the current state-of-the art of molecular imaging in the management of patients affected by inflammatory bowel disease(IBD).METHODS A systematic review of the literature was performed in order to find important original articles on the role of molecular imaging in the management of patients affected by IBD. The search was updated until February 2016 and limited to articles in English.RESULTS Fifty-five original articles were included in this review, highlighting the role of single photon emission tomography and positron emission tomography. CONCLUSION To date, molecular imaging represents a useful tool to detect active disease in IBD. However, the available data need to be validated in prospective multicenter studies on larger patient samples.

MINIMIZING EXCITATION LIGHT LEAKAGE AND MAXIMIZING MEASUREMENT SENSITIVITY FOR MOLECULAR IMAGING WITH NEAR-INFRARED FLUORESCENCE

Near-infraredfluorescence(NIRF)imaging involves the separation of weakfluorescence signals from backscattered excitation light.The measurement sensitivity of current NIRF imaging systems is limited by the excitation light leakage through rejectionfilters.In this contribution,the authors demonstrate that the excitation light leakage can be suppressed upon using appropriatefilter combination and permutations.The excitation light leakage and measurement sensitivity were assessed and compared in this study by computing the transmission ratios of excitation to emission light collected and the signal-to-noise ratios in well-controlled phantom studies with differentfilter combinations and permutations.Using appropriatefilter combinations and permutations,we observe as much as two orders of magnitude reduction in the transmission ratio and higher signal-to-noise ratio.

The First Congress of New Development on Molecular Imaging Dec 22 to 24,2011,Guangzhou,China

"The First Congress of New Development on Molecular Imaging" will be held in Guangdong Hotel in Guangzhou, Guangdong province, Dec 22 to 24, 2011. This conference is hosted by Ultrasound Medical Branch of Guangdong Medical Association, Ultrasound Medical Branch of Guangzhou Medical Association, is undertaken by

Photoacoustic molecular imaging with functional nanoparticles

Photoacoustic imaging(PAI)breaks through the optical di®usion limit by making use of the PA e®ect.By converting incident photons into ultrasonic waves,PAI combines high contrast of optical imaging and high spatial resolution in depth tissue of ultrasound imaging in a single imaging modality.This imaging modality has now shown potential for molecular imaging,which enables visualization of biological processes with systemically introduced functional nanoparticles.In the current review,the potentials of di®erent optical nanoprobes as PAI contrast agents were elucidated and discussed.

Spectral selective fluorescence molecular imaging with volume holographic imaging system

A compact volume holographic imaging(VHI)method that can detect fluorescence objects located in diffusive medium in spectral selective imaging manner is presented.The enlargement of lateralfield of view of the VHI system is realized by using broadband illumination and demagnification optics.Each target spectrum of°uorescence emitting from a di®usive medium is probed by tuning the inclination angle of the transmission volume holographic grating(VHG).With the use of the single transmission VHG,fluorescence images with different spectrum are obtained sequentially and precise three-dimensional(3D)information of deep fluorescent objects located in a diffusive medium can be reconstructed from these images.The results of phantom experiments demonstrate that two fluorescent objects with a sub-millimeter distance can be resolved by spectral selective imaging.

Molecular imaging as a tool for evaluation of COVID-19 sequelae-A review of literature

Coronavirus disease 2019(COVID-19)is caused by the novel viral pathogen,severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).COVID-19 primarily involves the lungs.Nucleic acid testing based on reverse-transcription polymerase chain reaction of respiratory samples is the current gold standard for the diagnosis of SARS-CoV-2 infection.Imaging modalities have an established role in triaging,diagnosis,evaluation of disease severity,monitoring disease progression,extra-pulmonary involvement,and complications.As our understanding of the disease improves,there has been substantial evidence to highlight its potential for multi-systemic involvement and development of longterm sequelae.Molecular imaging techniques are highly sensitive,allowing noninvasive visualization of physiological or pathological processes at a cellular or molecular level with potential for detection of functional changes earlier than conventional radiological imaging.The purpose of this review article is to highlight the evolving role of molecular imaging in evaluation of COVID-19 sequelae.Though not ideal for diagnosis,the various modalities of molecular imaging play an important role in assessing pulmonary and extra-pulmonary sequelae of COVID-19.Perfusion imaging using single photon emission computed tomography fused with computed tomography(CT)can be utilized as a first-line imaging modality for COVID-19 related pulmonary embolism.^(18)F-fluorodeoxyglucose positron emission tomography(PET)/CT is a sensitive tool to detect multi-systemic inflammation,including myocardial and vascular inflammation.PET in conjunction with magnetic resonance imaging helps in better characterization of neurological sequelae of COVID-19.Despite the fact that the majority of published literature is retrospective in nature with limited sample sizes,it is clear that molecular imaging provides additional valuable information(complimentary to anatomical imaging)with semi-quantitative or quantitative parameters to define inflammatory burden and can be used to guide therapeutic strategies and assess response.However,widespread clinical applicability remains a challenge owing to longer image acquisition times and the need for adoption of infection control protocols.

X-ray luminescence computed tomography:an emerging molecular imaging modality

X-ray luminescence computed tomography(XLCT) is an emerging hybrid imaging modality that can be used as a new tool in molecular imaging. XLCT has the potential to achieve the high spatial resolution of X-ray imaging and the high sensitivity feature of optical imaging in deep tissues. In XLCT,high energy X-ray photons are used to excite X-ray excitable particles emitting optical photons to be measured for reconstruction of the particle distribution inside tissues. Numerical simulations and experimental studies have been performed and proved that XLCT is suitable for in vivo small animal imaging. The aim of this review paper is to introduce the background of XLCT and to detail the concept of XLCT,including a brief review of tw o types of XLCT imaging system designs. The major challenges in the development of XLCT are also described. Finally,the future applications and development directions of XLCT are discussed.

Recent Advances in Activatable Probes for Molecular Imaging by Stimuli-Controlled Disassembly

Comprehensive Summary,Stimuli-controlled disassembly process has shown promise to direct delivery of probes and/or spatial-temporally control imaging signals for molecular imaging in vivo.Via the disassembly process,well defined nanoprobes with a stimulus-responsive moiety can be controllably converted into small-molecular imaging agents in response to a stimulus,leading to a switch in imaging signals.Moreover,the on-site released small-molecule probes could enhance penetration into the deep tissue for improved imaging of deep-seated molecular targets.Therefore,such a stimuli-controllable disassembly approach has been widely utilized to build activatable molecular imaging probes for the noninvasive detection of various molecular targets in living subjects.In this review article,we first briefly introduce the general principle of stimuli-controlled disassembly.We then summarize the activatable probes based on different internal or external stimulus that has been utilized to control disassembly process.Activatable probes by using multiple stimuli to control cascaded in situ self-assembly and disassembly processes are also discussed.Finally,we close with a conclusion of current challenges and perspective in this field.

Molecular imaging:design mechanism and bioapplications

Molecular imaging is a non-invasive method to image and analyze the concentration and activity of functional biomolecules in cells or in vivo at molecular level,and plays an increasing role in deep understanding of biological processes,early and accurate diagnosis of diseases,and evaluation of treatment.Nowadays,numerous novel molecular imaging probes have been developed,involving every biomedical imaging modality,such as optical imaging,photoacoustic imaging,magnetic resonance imaging,single-photon-emission computed tomography,and positron emission tomography.In this review,we summarize the development of current state-of-the-art molecular imaging probes.We introduce the design strategies of molecular probes and detailed imaging modalities,and highlight the properties of probes and biomedical imaging applications in cells and in vivo,including disease diagnosis,drug tracking,and imaging-guided surgery.Then we discuss the perspectives and challenges in this emerging field.We expect this review could inspire more effective molecular imaging probes to be developed,achieving the goal towards clinical practices.

Sequential ultrasound molecular imaging for noninvasive identification and assessment of non-alcoholic steatohepatitis in mouse models

Background and objective:Noninvasive non-alcoholic steatohepatitis(NASH)assessment is a clinical challenge to the management of non-alcoholic fatty liver disease.We aim to develop diagnostic models based on sequential ultrasound molecular imaging(USMI)for the noninvasive identification of NASH in mouse models.Methods:Animal experiments were approved by the Animal Ethics Committee of South China Agricultural University.Forty-nine C57BL/6 mice were divided into normal control,non-alcoholic fatty liver,NASH,and hepatitis groups.Sequential USMI was implemented using CD36-targeted microbubbles(MBs-CD36)and intercellular adhesion molecule-1(ICAM-1)-targeted microbubbles(MBs-ICAM-1)to visualize hepatic steatosis and inflammation.The targeting signal of USMI was quantified as the normalized intensity difference(NID)with the destruction-replenishment method.Correlation analysis was conducted between the NID-MBs-CD36 and pathological steatosis score and between the NID-MBsICAM-1 and pathological inflammation score.Finally,diagnostic models combining NID-MBs-CD36 with NID-MBs-ICAM-1 were established for NASH diagnosis.Results:MBs-CD36 and MBs-ICAM-1 were successfully prepared and used for sequential USMI in all mice.NID-MBs-CD36 values increased with the progression of steatosis,while NID-MBs-ICAM-1 values increased in parallel with the progression of inflammation.A strong positive correlation was identified between NID-MBs-CD36 and pathological steatosis grade(r_(s)=0.9078,P<0.0001)and between NIDMBs-ICAM-1 and pathological inflammation grade(r_(s)=0.9071,P<0.0001).Among various sequential USMI-based diagnostic models,the serial testing model showed high diagnostic performance in detecting NASH,with 95%sensitivity,97%specificity,95%positive predictive values,97%negative predictive values,and 96%accuracy.Conclusions:Sequential USMI using MBs-CD36 and MBs-ICAM-1 allows noninvasive grading of hepatic steatosis and inflammation.Sequential USMI-based diagnostic models hold great potential in the noninvasive identification of NASH.