<Emphasis Type="Italic">In Vivo</Emphasis> MR Imaging of Dual MRI Reporter Genes and Deltex-1 Gene-modified Human Mesenchymal Stem Cells in the Treatment of Closed Penile Fracture

Purpose

The purpose of this study was to investigate the feasibility of dual magnetic resonance imaging (MRI) reporter genes, including ferritin heavy subunit (Fth) and transferrin receptor (TfR), which provide sufficient MRI contrast for in vivo MRI tracking, and the Deltex-1 (DTX1) gene, which promotes human mesenchymal stem cell (hMSC) differentiation to smooth muscle cells (SMCs), to treat closed penile fracture (CPF).

Methods

Multi-gene co-expressing hMSCs were generated. The expression of mRNA and proteins was assessed, and the original biological properties of hMSCs were determined and compared. The intracellular uptake of iron was evaluated, and the ability to differentiate into SMCs was detected. Fifty rabbits with CPF were randomly transplanted with PBS, hMSCs, Fth-TfR-hMSCs, DTX1-hMSCs, and Fth-TfR-DTX1-hMSCs. In vivo MRI was performed to detect the distribution and migration of the grafted cells and healing progress of CPF, and the results were correlated with histology.

Results

The mRNA and proteins of the multi-gene were highly expressed. The transgenes could not influence the original biological properties of hMSCs. The dual MRI reporter genes increased the iron accumulation capacity, and the DTX1 gene promoted hMSC differentiation into SMCs. The distribution and migration of the dual MRI reporter gene-modified hMSCs, and the healing state of CPF could be obviously detected by MRI and confirmed by histology.

Conclusion

The dual MRI reporter genes could provide sufficient MRI contrast, and the distribution and migration of MSCs could be detected in vivo. The DTX1 gene can promote MSC differentiation into SMCs for the treatment of CPF and effectively inhibit granulation tissue formation.

     

Detection of Brain Tumors and Systemic Metastases Using NanoLuc and Fluc for Dual Reporter Imaging

Purpose

Bioluminescence imaging (BLI) is a technique with a low background noise and high sensitivity which is widely used in mice models in oncology. We aimed to assess BLI efficiency of the new luciferase NanoLuc (Nluc) for glioblastoma cell lines and tumors, including for dual reporter applications of deep brain tumors and systemic metastasis when combined with firefly luciferase (Fluc).

Procedures

U87 cells were genetically modified for constitutive production of either Nluc, Fluc, or both and assayed for luciferase activity and BLI on cell lysates, living cells, subcutaneous tumors, brain tumors, and systemic metastases.

Results

In vitro, light production by Nluc activity is higher than Fluc. In vivo, Nluc allows for tumor detection including for deep brain tumors and systemic metastases.

Conclusions

Nluc appears to be a useful tool to combine with Fluc for dual imaging in vivo using bioluminescence, allowing for the detection of distinct events in deep tissues within the same organism.

     

Reactive Oxygen Species Imaging in a Mouse Model of Inflammatory Bowel Disease

Purpose

Reactive oxygen species (ROS) are important contributors to inflammatory bowel disease (IBD); however, there are insufficient tools for their in vivo evaluation.

Procedures

To determine if a chemiluminescent ROS reporter, coelenterazine, would be a useful tool for the detection of immune cell activation, the macrophage cell line (RAW 264.7) was treated with phorbol myristate acetate (PMA). Additionally, coelenterazine was used to monitor the changes in ROS production over time in a mouse model of IBD.

Results

In vitro, coelenterazine enabled the dynamic monitoring of the RAW 264.7 cell oxidative burst. In vivo, there were early, preclinical, changes in the localization and magnitude of coelenterazine chemiluminescent foci.

Conclusions

Coelenterazine offers a high-throughput method for assessing immune cell activation in culture and provides a means for the in vivo detection and localization of ROS during IBD disease progression.

     

Bioluminescence Imaging of Colonization and Clearance Dynamics of <Emphasis Type="Italic">Brucella Suis</Emphasis> Vaccine Strain S2 in Mice and Guinea Pigs

Purpose

The goal of this study was to develop a plasmid-based lux bio-reporter for use to obtain in vivo images of Brucella suis vaccine strain 2 (B.suis S2) infection with high resolution and good definition.

Procedures

The pBBR-lux (pBBR1MCS-2-lxCDABE) plasmid that carries the luxCDABE operon was introduced into B. suis S2 by electroporation yielding B. suis S2-lux. The spatial and temporal transit of B. suis S2 in mice and guinea pigs was monitored by bioluminescence imaging.

Results

The plasmid pBBR-lux is stable in vivo and does not appear to impact the virulence or growth of bacteria. This sensitive luciferase reporter could represent B. suis S2 survival in real time. B. suis S2 mainly colonized the lungs, liver, spleen, and uterus in mice and guinea pigs as demonstrated by bioluminescence imaging.

Conclusion

The plasmid-based lux bioreporter strategy can be used to obtain high resolution in vivo images of B. suis S2 infection in mice and guinea pigs.

     

Tri-modal <Emphasis Type="Italic">In vivo</Emphasis> Imaging of Pancreatic Islets Transplanted Subcutaneously in Mice

Purpose

Transplantation of pancreatic islets (PIs) is a promising therapeutic approach for type 1 diabetes. The main obstacle for this strategy is that the outcome of islet engraftment depends on the engraftment site. It was our aim to develop a strategy for using non-invasive imaging techniques to assess the location and fate of transplanted PIs longitudinally in vivo.

Procedures

In order to overcome the limitations of individual imaging techniques and cross-validate findings by different modalities, we have combined fluorine magnetic resonance imaging (F-19 MRI), fluorescence imaging (FLI), and bioluminescent imaging (BLI) for studying subcutaneously transplanted PIs and beta cell-like cells (INS-1E cell line) in vivo. We optimized the transduction (using lentiviral vectors) and labeling procedures (using perfluoro crown ether nanoparticles with a fluorescence dye) for PIs and INS-1E cell imaging.

Results

The feasibility of using the proposed imaging methods for PI assessment was demonstrated both in vitro and in vivo. Our data suggested that F-19 MRI is suitable for high-resolution localization of transplanted cells and PIs; FLI is essential for confirmation of contrast localization by histology; and BLI is a reliable method to assess cell viability and survival after transplantation. No significant side effects on cell viability and function have been observed.

Conclusions

The proposed tri-modal imaging platform is a valuable approach for the assessment of engrafted PIs in vivo. It is potentially suitable for comparing different transplantation sites and evaluating novel strategies for improving PI transplantation technique in the future.

     

Multimodality Imaging of Cancer Superoxide Anion Using the Small Molecule Coelenterazine

Purpose

We evaluated the small molecule coelenterazine as a potential reporter of cancer-associated superoxide anion in cell culture and in mice.

Procedures

The superoxide anion concentrations of various cancer cell lines were quantified by coelenterazine chemiluminescence in vitro. Coelenteramide fluorescence was detected via flow cytometry and fluorescent microscopy. Coelenterazine was used for the in vivo detection of cancer-associated superoxide anion using the 4T1 breast adenocarcinoma mouse model.

Results

Various cell lines in culture demonstrated different superoxide anion concentrations, with a signal range of 3.15?±?0.06 to 11.80?±?0.24 times that of background. In addition to chemiluminescent detection of coelenterazine, we demonstrated fluorescent detection of coelenteramide within the cytoplasm of cells. 4T1 murine mammary adenocarcinoma tumors in mice demonstrated significantly higher 2.13?±?0.19-fold coelenterazine-based chemiluminescence than that of surrounding normal tissues.

Conclusions

Collectively, our results indicate that coelenterazine can be used to assay superoxide anion concentrations in cultured cancer cells and in tumors growing in mice.

     

Multimodal Genetic Approach for Molecular Imaging of Vasculature in a Mouse Model of Melanoma

Purpose

In this study, we evaluated a genetic approach for in vivo multimodal molecular imaging of vasculature in a mouse model of melanoma.

Procedures

We used a novel transgenic mouse, Ts-Biotag, that genetically biotinylates vascular endothelial cells. After inoculating these mice with B16 melanoma cells, we selectively targeted endothelial cells with (strept)avidinated contrast agents to achieve multimodal contrast enhancement of Tie2-expressing blood vessels during tumor progression.

Results

This genetic targeting system provided selective labeling of tumor vasculature and showed in vivo binding of avidinated probes with high specificity and sensitivity using microscopy, near infrared, ultrasound, and magnetic resonance imaging. We further demonstrated the feasibility of conducting longitudinal three-dimensional (3D) targeted imaging studies to dynamically assess changes in vascular Tie2 from early to advanced tumor stages.

Conclusions

Our results validated the Ts-Biotag mouse as a multimodal targeted imaging system with the potential to provide spatio-temporal information about dynamic changes in vasculature during tumor progression.

     

Effet des extraits de quelques plantes sur les bactéries pathogènes responsables de gastroentérites

Background

Phytochemicals are natural bioactive compounds that protect plants against the stress. These phytochemicals may also have other biological activities like, antibacterial activity.

Objective

The objective of this work is to study the antibacterial effect of aqueous and hydro-alcoholic extracts prepared from Thymus vulgaris, Aloysia triphylla, Pistacia lentiscus, Olea europaea leaves and Trigonella foenum-graecum seeds on some pathogenic bacteria responsible for gastroenteritis.

Result

The results obtained from the antibacterial effect showed a moderate activity against the strains studied with a diameters of inhibition zones ranging from 07.00 ± 0.8 to 16.00 ± 1.0 mm for aqueous extracts and vary between 07.00 ± 0.9 and 13.00 ± 1.0 mm for hydro-alcoholic extracts.

Conclusion

This study confirms the possibility of using these plants or components in the prevention of several diseases like, gastroenteritis.

     

<Emphasis Type="Italic">In</Emphasis><Emphasis Type="Italic">Vivo</Emphasis> Bioluminescence Imaging of Transplanted Mesenchymal Stromal Cells and Their Rejection Mediated by Intrahepatic NK Cells

Purpose

Mesenchymal stromal cells (MSCs) hold promise in the treatment of liver disease. However, short survival time of MSCs after intrahepatic transplantation limits their value; therefore, understanding the basis of MSCs survival and rejection may increase their utility. This study was aimed at determining the role of intrahepatic natural killer (NK) cells on MSCs survival and their retention in the liver shortly after transplant.

Procedures

Human MSCs were labeled with the Luc2-mKate2 dual-fusion reporter gene (MSCs-R), and the residence time and survival of MSCs-R xenografts after intrahepatic transplantation were evaluated by in vivo bioluminescence imaging (BLI). Coculture of MSCs and NK cells was performed to assess cytotoxicity. To evaluate the role of NK cells in rejection of the xenografted cells, the fates of transplanted MSCs-R were then assessed in vivo by BLI after activation of intrahepatic NK cells.

Results

We observed a linear correlation between luciferase activity from live MSCs-R and cell number in vitro (R ²?=?0.9956). In vivo, we observed a gradual decline in bioluminescent signals from transplanted MSCs-R over a region corresponding to the liver in both the control group and the NK-activated group. However, the survival time and retention of intrahepatic MSCs-R decreased more rapidly in the NK-activated group of mice compared to the control group. This indicated that activated NK cells accelerate the elimination of transplanted MSCs. Also, we found that the number of hepatic NK cells and the expression of NK activation markers significantly increased after intrahepatic delivery of MSCs. This suggested that resident NK cells, in a resting state, were activated by intrahepatic transplantation of human MSCs. Taken together, the data suggests that activated hepatic NK cells mediate, in part, rejection of the MSCs xenografts. Cytotoxicity assays showed that activated NK cells may inhibit the proliferation of MSCs and, to a certain extent, induce MSCs death.

Conclusion

Human MSCs could be followed dynamically in vivo by BLI, and the role of murine hepatic NK cells, especially activated NK cells, could be inferred from the loss of signals from MSCs. This finding may have practical clinical implications in MSCs transplantation in treating liver disease.

     

Imaging Early Fate of Cancer Stem Cells in Mouse Hindlimbs with Sodium Iodide Symporter Gene and I-124 PET

Purpose

We investigated the capacity of sodium/iodide symporter (NIS) positron emission tomography (PET) to image and quantitate early engraftment and survival of cancer stem cells (CSCs) in living mice.

Procedures

CT26 colon cancer cells and CSCs were infected with an adenovirus expressing both NIS and enhanced green fluorescent protein (EGFP). Cells were implanted into normal and ischemic hindlimbs of mice, and serial optical and I-124 PET imaging was performed. Extracted tissues underwent I-124 measurements and confocal microscopy.

Results

NIS.EGFP gene transfer increased fluorescence and I-124 uptake of CSCs and CT26 cells without adverse effects. I-124 PET clearly visualized implanted tumor cells in vivo, whereas optical imaging was suboptimal. PET revealed 1.95, 2.22, and 1.93-fold greater I-124 uptake by CSC inoculation into ischemic compared to non-ischemic limbs at 2, 15, and 24 h, respectively. CT26 cells showed similar but smaller differences. PET findings were confirmed by ex vivo measurements and confocal microscopy.

Conclusions

NIS PET can help identify microenvironment conditions that influence early survival of implanted CSCs.

     

Bioluminescence Imaging for Monitoring miR-200c Expression in Breast Cancer Cells and its Effects on Epithelial-Mesenchymal Transition Progress in Living Animals

Purpose

Dysregulation of microRNAs (miRNAs) are not only involved in the formation of malignant tumors but also in the processes of differentiation and aggressiveness. However, current methods for detecting miRNA expression have major disadvantages, such as being invasive and non-reproducible. The epithelial-mesenchymal transition (EMT) has been implicated as a pivotal event in the metastasis, stemness, and chemoresistance of malignant tumors.

Procedures

In our study, we constructed a new reporter gene, Luc2/tdT_miR200c_3TS, to examine the in vitro and in vivo expression of miR-200c, an EMT-associated miRNA. Quantitative real-time PCR was used to measure the expression levels of miR-200c and EMT-related mRNA, and luciferase assay and bioluminescence imaging were used to measure the luciferase activities in vitro and in vivo, respectively.

Results

We found that the expression level of miR-200c was negatively associated with cell migration and invasion. Luciferase activities were regulated by the differential expression levels of miR-200c and EMT process.

Conclusions

Our results demonstrate that Luc2/tdT_miR200c_3TS may be a useful tool for monitoring the expression level of miR-200c at both the cellular level and in living animals, thereby providing a potential high-throughput approach for anticancer drug screening.

     

Predictive factors for polypharmacy among child and adolescent psychiatry inpatients

Background

Aim was to determine the predictive factors for polypharmacy among inpatient children and adolescents with psychiatric disorders.

Methods

Blinded, case-note review of children and adolescents with ICD 10 diagnosis of psychiatric disorders on psychotropic medication was conducted. Data on demography, illness, and treatment was analyzed with univariate and multivariate techniques.

Results

Proscribing non-pharmacological interventions (OR = 4.7) and pro re nata medication (OR = 3.3), increased the risk of polypharmacy. Prescribing physical restraint reduced the risk of receiving multiple medications (OR = 0.3).

Conclusion

Proscribing non-pharmacological interventions, pro re nata medication and physical restraints increased polypharmacy.

     

<Emphasis Type="Italic">Staphylococcus aureus</Emphasis> Evasion of Host Immunity in the Setting of Prosthetic Joint Infection: Biofilm and Beyond

Purpose of Review

The incidence of complications from prosthetic joint infection (PJI) is increasing, and treatment failure remains high. We review the current literature with a focus on Staphylococcus aureus pathogenesis and biofilm, as well as treatment challenges, and novel therapeutic strategies.

Recent Findings

S. aureus biofilm creates a favorable environment that increases antibiotic resistance, impairs host immunity, and increases tolerance to nutritional deprivation. Secreted proteins from bacterial cells within the biofilm and the quorum-sensing agr system contribute to immune evasion. Additional immunoevasive properties of S. aureus include the formation of staphylococcal abscess communities (SACs) and canalicular invasion. Novel approaches to target biofilm and increase resistance to implant colonization include novel antibiotic therapy, immunotherapy, and local implant treatments.

Summary

Challenges remain given the diverse mechanisms developed by S. aureus to alter the host immune responses. Further understanding of these processes should provide novel therapeutic mechanisms to enhance eradication after PJI.

     

Generation and Application of Male Mice with Specific Expression of Green Fluorescent Protein in Germ Cells

Purpose

The study aimed to generate a mouse line with green fluorescent protein (GFP) specifically expressed in male germ cells to assess testicular toxicity.

Procedures

The mouse line with GFP specifically expressed in male germ cells was generated by mating a germ cell-specific transgenic Cre male mouse with a double-fluorescent reporter female mouse using Cre/loxP. The mouse line was administered ethylene glycol monomethyl ether (EGME) by oral gavage. Then, the green fluorescence intensity in the testes was used as an indicator to examine the potential for testicular toxicity testing by molecular biology, histopathology, and in vivo imaging techniques.

Results

Specific testicular GFP expression was observed in mice. GFP was mainly expressed in the germ cell lineage and concentrated in secondary spermatocytes/spermatocytes and spermatozoa. After administration of EGME, at the organ level, the green fluorescent intensity of the testes was decreased by 11 days and had disappeared by 34 days. Frozen testicular sections stained with DAPI showed significantly decreased green fluorescence in secondary spermatocytes and sperm cells. These observations were consistent with the testis weight and results of testicular histopathology.

Conclusions

With the application of in vivo imaging becoming popular, this mouse line with GFP specifically expressed in the male germ cells may have some advantages for the study of reproductive toxicity.

     

Current and Emerging Treatment Modalities for Leber’s Hereditary Optic Neuropathy: A Review of the Literature

Introduction

The purpose of this review is to present the current and emerging treatment alternatives for Leber’s hereditary optic neuropathy (LHON), emphasizing the most recent use of idebenone and stem cells or gene therapy.

Methods

A comprehensive literature review was performed at the PubMed database regarding the various treatment modalities for LHON.

Results

Treatment modalities for LHON include nutritional supplements, activators of mitochondrial biogenesis, brimonidine, and symptomatic and supportive treatment, but nowadays attention is being paid to idebenone and gene therapy or stem cells.

Conclusion

The treatment of LHON remains challenging, given the nature of the disease and its prognosis.

     

Gallium-68 Complexes Conjugated to Pittsburgh Compound B: Radiolabeling and Biological Evaluation

Purpose

The aim of this work is to develop an efficient and fully automated radiosynthesis of three derivatives of the Pittsburgh compound B labeled with gallium-68 for the detection of amyloid plaques.

Procedures

The radiolabeling of the precursors and purification of the radiolabeled agents by high pressure liquid chromatography has been studied prior to their in vitro and in vivo evaluations.

Results

The complete process led, in 50 min, to pure Ga-68 products in a 12–38 % yield and with appreciable specific radioactivity (SRA, 85–168 GBq/μmol) which enabled us to demonstrate a considerable in vivo stability of the products. Unfortunately, this result was associated with a poor blood–brain barrier (BBB) permeability and a limited uptake of our compounds by amyloid deposits was observed by in vitro autoradiography.

Conclusion

Although we have not yet identified a compound able to significantly mark cerebral amyloidosis, this present investigation will likely contribute to the development of more successful Ga-68 radiotracers.

     

Effect of synbiotic therapy on the incidence of ventilator associated pneumonia in critically ill patients: a randomised,double-blind,placebo-controlled trial

Objective

To investigate the effect of enteral Synbiotic 2000 FORTE^® (a mixture of lactic acid bacteria and fibre) on the incidence of ventilator associated pneumonia (VAP) in critically ill patients.

Design

Prospective, randomised, double blind, placebo controlled trial.

Setting

Tertiary referral centre, general Adult Intensive Care Unit (ICU).

Patients and participants

259 enterally fed patients requiring mechanical ventilation for 48 h or more were enrolled.

Intervention

All patients were enterally fed as per a standard protocol and randomly assigned to receive either synbiotic 2000 FORTE^® (twice a day) or a cellulose-based placebo for a maximum of 28 days.

Measurements and results

Treatment group (n = 130) was well matched with placebo group (n = 129) for age (mean 49.5 and 50 years, respectively) and APACHE II score (median 17 for both). Oropharyngeal microbial flora and colonisation rates were unaffected by synbiotics. The overall incidence of VAP was lower than anticipated (11.2%) and no statistical difference was demonstrated between groups receiving synbiotic and placebo in the incidence of VAP (9 and 13%, P = 0.42), VAP rate per 1,000 ventilator days (13 and 14.6, P = 0.91) or hospital mortality (27 and 33%, P = 0.39), respectively.

Conclusions

Enteral administration of Synbiotic 2000 FORTE^® has no statistically significant impact on the incidence of VAP in critically ill patients.

     

Long-term Efficacy of Safinamide on Parkinson’s Disease Chronic Pain

Introduction

Chronic pain is an important yet overlooked non-motor symptom of Parkinson’s disease (PD), caused by an imbalance of the dopaminergic and glutamatergic systems. Safinamide has a multimodal mechanism of action, dopaminergic (reversible MAO-B inhibition) and non-dopaminergic (modulation of the abnormal glutamate release), that might be beneficial for both motor and non-motor symptoms.

Objectives

To investigate the long-term (2-year) efficacy of safinamide on PD chronic pain and to confirm the positive effects observed after 6 months of treatment.

Methods

This is a post hoc analysis of the data from the 2-year study 018, focused on the reduction of concomitant pain treatments and on the scores of pain-related items of the Parkinson’s disease quality of life questionnaire (PDQ-39).

Results

Safinamide, compared with placebo, significantly improved the PDQ-39 items 37 (“painful cramps or spasm,” p?=?0.0074) and 39 (“unpleasantly hot or cold,” p?=?0.0209) and significantly reduced the number of concomitant pain treatments by 26.2% (p?=?0.005). A significantly greater proportion of patients in the safinamide group was not using pain drugs after 2 years of treatment (p?=?0.0478).

Conclusions

The positive effects of safinamide on PD chronic pain were maintained in the long term. Further investigations are desirable to confirm their clinical relevance.

Funding

Zambon SpA.

     

Bioluminescence Imaging to Monitor the Effects of the Hsp90 Inhibitor NVP-AUY922 on NF-κB Pathway in Endometrial Cancer

Purpose

In this study, we first aimed to evaluate the effects in vitro and in vivo, of the Hsp90 inhibitor NVP-AUY922, in endometrial cancer (EC). We also aimed to track nuclear factor kappa B (NF-κB) signalling, a key pathway involved in endometrial carcinogenesis and to check whether NVP-AUY922 treatment modulates it both in vitro and in vivo.

Procedures

I n vitro effects of NVP-AUY922 on EC cell growth and the signalling pathways were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), clonogenic assays, Western Blot and luciferase assay. NVP-AUY922 effect on Ishikawa (IK) xenograft growth was evaluated in vivo, and NF-κB activity was monitored using bioluminescence imaging.

Results

NVP-AUY922 inhibited the growth of three endometrial cell lines tested in vitro. In vivo, NVP-AUY922 reduced tumour growth of 47 % (p?=?0.042) compared to control condition. Moreover, the bioluminescence signal of the tumours harbouring IK NF-κB-LUC cells was significantly reduced in NVP-AUY922-treated animals compared to untreated ones.

Conclusions

NVP-AUY922 reduced EC tumour growth and NF-κB signalling both in vitro and in vivo. As therapeutic resistance of EC remains a challenge for oncologists nowadays, we think that NVP-AUY922 represents a valid alternative to conventional chemotherapy, and we believe that this approach for assessing and tracking the activation of NF-κB pathway may be of therapeutic benefit.

     

Using Dual Fluorescence Reporting Genes to Establish an <Emphasis Type="Italic">In Vivo</Emphasis> Imaging Model of Orthotopic Lung Adenocarcinoma in Mice

Purpose

Lung adenocarcinoma is characterized by a poor prognosis and high mortality worldwide. In this study, we purposed to use the live imaging techniques and a reporter gene that generates highly penetrative near-infrared (NIR) fluorescence to establish a preclinical animal model that allows in vivo monitoring of lung cancer development and provides a non-invasive tool for the research on lung cancer pathogenesis and therapeutic efficacy.

Procedures

A human lung adenocarcinoma cell line (A549), which stably expressed the dual fluorescence reporting gene (pCAG-iRFP-2A-Venus), was used to generate subcutaneous or orthotopic lung cancer in nude mice. Cancer development was evaluated by live imaging via the NIR fluorescent signals from iRFP, and the signals were verified ex vivo by the green fluorescence of Venus from the gross lung. The tumor-bearing mice received miR-16 nucleic acid therapy by intranasal administration to demonstrate therapeutic efficacy in this live imaging system.

Results

For the subcutaneous xenografts, the detection of iRFP fluorescent signals revealed delicate changes occurring during tumor growth that are not distinguishable by conventional methods of tumor measurement. For the orthotopic xenografts, the positive correlation between the in vivo iRFP signal from mice chests and the ex vivo green fluorescent signal from gross lung tumors and the results of the suppressed tumorigenesis by miR-16 treatment indicated that lung tumor size can be accurately quantified by the emission of NIR fluorescence. In addition, orthotopic lung tumor localization can be accurately visualized using iRFP fluorescence tomography in vivo, thus revealing the trafficking of lung tumor cells.

Conclusions

We introduced a novel dual fluorescence lung cancer model that provides a non-invasive option for preclinical research via the use of NIR fluorescence in live imaging of lung.