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1.
Tom Völler Andreas Faust Johannes Roth Michael Schäfers Thomas Vogl Sven Hermann 《Molecular imaging and biology》2018,20(3):407-416
Purpose
Non-invasive assessment of inflammatory activity in the course of various diseases is a largely unmet clinical challenge. An early feature of inflammation is local secretion of the alarmin S100A8/A9 by activated phagocytes. We here evaluate a novel S100A9-targeted small molecule tracer Cy5.5-CES271 for in vivo optical imaging of inflammatory activity in exemplary disease models.Procedures
Dynamics of Cy5.5-CES271 was characterized in a model of irritant contact dermatitis by sequential fluorescence reflectance imaging (FRI) up to 24 h postinjection (p.i.). Specificity of Cy5.5-CES271 binding to S100A9 in vivo was examined by blocking studies and by employing S100A9?/? mice. Finally, S100A9 secretion in acute lung inflammation was assessed by Cy5.5-CES271 and FRI of explanted lungs.Results
In ear inflammation, we were able to non-invasively follow the time course of S100A9 expression using Cy5.5-CES271 and FRI over 24 h p.i. (peak activity at 3 h p.i.). Specificity of imaging could be shown by a significant signal reduction after predosing and using S100A9?/? mice. In acute lung injury, local and systemic S100A8/A9 levels increased over time and correlated significantly with FRI signal levels in explanted lungs.Conclusions
Cy5.5-CES271 shows significant accumulation in models of inflammatory diseases and specific binding to S100A9 in vivo. This study, for the first time, demonstrates the potential of a small molecule non-peptidic tracer enabling imaging of S100A9 as a marker of local phagocyte activity in inflammatory scenarios suggesting this compound class for translational attempts.2.
Wuwei Ren Andreas Elmer David Buehlmann Mark-Aurel Augath Divya Vats Jorge Ripoll Markus Rudin 《Molecular imaging and biology》2016,18(2):191-200
Purpose
Assessing tumor vascular features including permeability and perfusion is essential for diagnostic and therapeutic purposes. The aim of this study was to compare fluorescence and magnetic resonance imaging (MRI)-based vascular readouts in subcutaneously implanted tumors in mice by simultaneous dynamic measurement of tracer uptake using a hybrid fluorescence molecular tomography (FMT)/MRI system.Procedure
Vascular permeability was measured using a mixture of extravascular imaging agents, GdDOTA and the dye Cy5.5, and perfusion using a mixture of intravascular agents, Endorem and a fluorescent probe (Angiosense). Dynamic fluorescence reflectance imaging (dFRI) was integrated into the hybrid system for high temporal resolution.Results
Excellent correspondence between uptake curves of Cy5.5/GdDOTA and Endorem/Angiosense has been found with correlation coefficients R?>?0.98. The two modalities revealed good agreement regarding permeability coefficients and centers-of-gravity of the imaging agent distribution.Conclusion
The FMT/dFRI protocol presented is able to accurately map physiological processes and poses an attractive alternative to MRI for characterizing tumor neoangiogenesis.3.
Cheng-Wei Lai Hsiao-Ling Chen Chih-Ching Yen Jiun-Long Wang Shang-Hsun Yang Chuan-Mu Chen 《Molecular imaging and biology》2016,18(6):849-859
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.4.
Laura L. Bronsart Christian Stokes Christopher H. Contag 《Molecular imaging and biology》2016,18(2):166-171
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.5.
Anna G. Sorace Anum K. Syed Stephanie L. Barnes C. Chad Quarles Violeta Sanchez Hakmook Kang Thomas E. Yankeelov 《Molecular imaging and biology》2017,19(1):130-137
Purpose
Evaluation of [18F]fluoromisonidazole ([18F]FMISO)-positron emission tomography (PET) imaging as a metric for evaluating early response to trastuzumab therapy with histological validation in a murine model of HER2+ breast cancer.Procedures
Mice with BT474, HER2+ tumors, were imaged with [18F]FMISO-PET during trastuzumab therapy. Pimonidazole staining was used to confirm hypoxia from imaging.Results
[18F]FMISO-PET indicated significant decreases in hypoxia beginning on day 3 (P?<?0.01) prior to changes in tumor size. These results were confirmed with pimonidazole staining on day 7 (P?<?0.01); additionally, there was a significant positive linear correlation between histology and PET imaging (r 2 ?=?0.85).Conclusions
[18F]FMISO-PET is a clinically relevant modality which provides the opportunity to (1) predict response to HER2+ therapy before changes in tumor size and (2) identify decreases in hypoxia which has the potential to guide subsequent therapy.6.
Laura Bronsart Linh Nguyen Aida Habtezion Christopher Contag 《Molecular imaging and biology》2016,18(4):473-478
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.7.
Marieke A. Stammes Vicky T. Knol-Blankevoort Luis J. Cruz Hans R. I. J. Feitsma Laura Mezzanotte Robert A. Cordfunke Riccardo Sinisi Elena A. Dubikovskaya Azusa Maeda Ralph S. DaCosta Katja Bierau Alan Chan Eric L. Kaijzel Thomas J. A. Snoeks Ermond R. van Beek Clemens W. G. M. Löwik 《Molecular imaging and biology》2016,18(6):905-915
Purpose
Recently we showed that a number of carboxylated near-infrared fluorescent (NIRF) cyanine dyes possess strong necrosis avid properties in vitro as well as in different mouse models of spontaneous and therapy-induced tumor necrosis, indicating their potential use for cancer diagnostic- and prognostic purposes. In the previous study, the detection of the cyanines was achieved by whole body optical imaging, a technique that, due to the limited penetration of near-infrared light, is not suitable for investigations deeper than 1 cm within the human body. Therefore, in order to facilitate clinical translation, the purpose of the present study was to generate a necrosis avid cyanine-based NIRF probe that could also be used for single photon emission computed tomography (SPECT). For this, the necrosis avid NIRF cyanine HQ4 was radiolabeled with 111indium, via the chelate diethylene triamine pentaacetic acid (DTPA).Procedures
The necrosis avid properties of the radiotracer [111In]DTPA-HQ4 were examined in vitro and in vivo in different breast tumor models in mice using SPECT and optical imaging. Moreover, biodistribution studies were performed to examine the pharmacokinetics of the probe in vivo.Results
Using optical imaging and radioactivity measurements, in vitro, we showed selective accumulation of [111In]DTPA-HQ4 in dead cells. Using SPECT and in biodistribution studies, the necrosis avidity of the radiotracer was confirmed in a 4T1 mouse breast cancer model of spontaneous tumor necrosis and in a MCF-7 human breast cancer model of chemotherapy-induced tumor necrosis.Conclusions
The radiotracer [111In]DTPA-HQ4 possessed strong and selective necrosis avidity in vitro and in various mouse models of tumor necrosis in vivo, indicating its potential to be clinically applied for diagnostic purposes and to monitor anti-cancer treatment efficacy.8.
Lieven Huang Vicky Caveliers Chris Vanhove Marleen Keyaerts Patrick De Baetselier Axel Bossuyt Hilde Revets Tony Lahoutte 《Molecular imaging and biology》2008,10(3):167-175
Purpose
Overexpression of the epidermal growth factor receptor (EGFR) occurs with high incidence in various carcinomas. The oncogenic expression of the receptor has been exploited for immunoglobulin-based diagnostics and therapeutics. We describe the use of a llama single-domain antibody fragment, termed Nanobody®, for the in vivo radioimmunodetection of EGFR overexpressing tumors using single photon emission computed tomography (SPECT) in mice.Methods
Fluorescence-activated cell sorting (FACS) analysis was performed to evaluate the specificity and selectivity of 8B6 Nanobody to bind EGFR on EGFR overexpressing cells. The Nanobody was then labeled with 99mTc via its C-terminal histidine tail. Uptake in normal organs and tissues was assessed by ex vivo analysis. In vivo tumor targeting of 99mTc-8B6 Nanobody was evaluated via pinhole SPECT in mice bearing xenografts of tumor cells with either high (A431) or moderate (DU145) overexpression of EGFR.Results
FACS analysis indicated that the 8B6 Nanobody only recognizes cells overexpressing EGFR. In vivo blood clearance of 99mTc-8B6 Nanobody is relatively fast (half-life, 1.5 h) and mainly via the kidneys. At 3 h postinjection, total kidney accumulation is high (46.6?±?0.9%IA) compared to total liver uptake (18.9?±?0.6%IA). Pinhole SPECT imaging of mice bearing A431 xenografts showed higher average tumor uptake (5.2?±?0.5%IA/cm3) of 99mTc-8B6 Nanobody compared to DU145 xenografts (1.8?±?0.3%IA/cm3, p?0.001).Conclusion
The EGFR-binding Nanobody investigated in this study shows high specificity and selectivity towards EGFR overexpressing cells. Pinhole SPECT analysis with 99mTc-8B6 Nanobody enabled in vivo discrimination between tumors with high and moderate EGFR overexpression. The favorable biodistribution further corroborates the suitability of Nanobodies for in vivo tumor imaging.9.
Li Gong Haiming Ding Nicholas E. Long Brandon J. Sullivan Edward W. MartinJr Thomas J. Magliery Michael F. Tweedle 《Molecular imaging and biology》2018,20(1):47-54
Purpose
Optical surgical navigation (OSN) will be a potent tool to help surgeons more accurately and efficiently remove tumors. The purpose of this study was to evaluate a novel humanized 3E8 antibody (3E8 MAb) fragment site-specifically conjugated with IR800, 3E8.scFv.Cys-IR800, as a potential OSN agent to target colorectal adenocarcinoma.Procedures
An engineered single-chain variable fragment of 3E8 MAb (targeted to TAG-72), appending a C-terminal cysteine residue (3E8.scFv.Cys), was created and reacted with IRDye800-maleimide. 3E8.scFv.Cys-IR800 identity and purity were verified by MALDI-TOF mass spectra and 800 nm detected size exclusion column HPLC. In vitro human colon adenocarcinoma LS-174 T cells binding and competition assay validated biological functionality. We further evaluated the imaging ability and receptor-specific binding of 3E8.scFv.Cys-IR800 in an orthotopic LS-174 T mouse model.Results
A 1:1 dye to protein conjugate was achieved at greater than 90 % HPLC purity. A 1 nmol dose of 3E8.scFv.Cys-IR800 via intraperitoneal injection administration was sufficient to produce high tumor to background fluorescence contrast. Blocking competition studies both in vitro and in vivo using a different blocking protein, 3E8ΔCH2, demonstrated 3E8.scFv.Cys-IR800 binding specificity for TAG-72 antigen.Conclusions
3E8.scFv.Cys-IR800 shows properties useful in a clinically viable OSN agent for colorectal cancer.10.
Tetsuro Tago Shozo Furumoto Nobuyuki Okamura Ryuichi Harada Hajime Adachi Yoichi Ishikawa Kazuhiko Yanai Ren Iwata Yukitsuka Kudo 《Molecular imaging and biology》2016,18(2):258-266
Purpose
Noninvasive imaging of tau and amyloid-β pathologies would facilitate diagnosis of Alzheimer’s disease (AD). Recently, we have developed [18F]THK-5105 for selective detection of tau pathology by positron emission tomography (PET). The purpose of this study was to clarify biological properties of optically pure [18F]THK-5105 enantiomers.Procedures
Binding for tau aggregates in AD brain section was evaluated by autoradiography (ARG). In vitro binding assays were performed to evaluate the binding properties of enantiomers for AD brain homogenates. The pharmacokinetics in the normal mouse brains was assessed by ex vivo biodistribution assayResults
The ARG of enantiomers showed the high accumulation of radioactivity corresponding to the distribution of tau deposits. In vitro binding assays revealed that (S)-[18F]THK-5105 has slower dissociation from tau than (R)-[18F]THK-5105. Biodistribution assays indicated that (S)-[18F]THK-5105 eliminated faster from the mouse brains and blood compared with (R)-[18F]THK-5105.Conclusion
(S)-[18F]THK-5105 could be more suitable than (R)-enantiomer for a tau imaging agent.11.
Giselle A. Suero-Abreu Orlando Aristizábal Benjamin B. Bartelle Eugenia Volkova Joe J. Rodríguez Daniel H. Turnbull 《Molecular imaging and biology》2017,19(2):203-214
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.12.
Freddy E. Escorcia Jeffrey M. Steckler Dalya Abdel-Atti Eric W. Price Sean D. Carlin Wolfgang W. Scholz Jason S. Lewis Jacob L. Houghton 《Molecular imaging and biology》2018,20(5):808-815
Purpose
Tumor-specific molecular imaging is an important tool for assessing disease burden and treatment response. CA19.9 is an important tumor-specific marker in several malignancies, including urothelial carcinoma. [89Zr]DFO-HuMab-5B1 (MVT-2163) is a CA19.9-specific antibody-based construct that has been validated in preclinical animal models of lung, colorectal, and pancreatic malignancies for positron emission tomography (PET) imaging and is currently in a phase I trial for pancreatic cancer (NCT02687230). Here, we examine whether [89Zr]DFO-HuMab-5B1 may be useful in defining urothelial malignancies.Procedures
Surface expression of CA19.9 was confirmed in the human bladder cancer line HT 1197. The radioimmunoconjugate [89Zr]DFO-HuMab-5B1 was injected into mice bearing HT 1197 xenografts, and followed by PET imaging, ex vivo experiments including biodistribution, histology and autoradiography, and analysis of blood samples for shed antigen levels were performed.Results
[89Zr]DFO-HuMab-5B1 specifically accumulates in HT 1197 engrafted tumors when imaged with PET. Ex vivo biodistribution of organs and autoradiography of engrafted tumors confirm our construct’s specific tumor binding. The target antigen CA19.9 was not found to be shed in vitro or in vivo.Conclusions
[89Zr]DFO-HuMab-5B1 can be used to delineate urothelial carcinomas by PET imaging and may provide tumor-specific information prior to, during, and after systemic therapies.13.
Xiwen Wang Zhiping Li Bo Li Hang Chi Jiakuan Li Hongchao Fan Ruizhi Yao Qianxue Li Xiaolin Dong Man Chen Han Qu Yuanyuan Wang Weicun Gao Yutian Wang Yu Sun Rui Sun Jun Qian Zhiping Xia 《Molecular imaging and biology》2016,18(4):519-526
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.14.
Sayuan Liang Karim Louchami Bryan Holvoet Rein Verbeke Christophe M. Deroose Bella Manshian Stefaan J. Soenen Ine Lentacker Uwe Himmelreich 《Molecular imaging and biology》2018,20(6):940-951
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.15.
Mohamed Hassanein Matthew R. Hight Jason R. Buck Mohammed N. Tantawy Michael L. Nickels Megan D. Hoeksema Bradford K. Harris Kelli Boyd Pierre P. Massion H. Charles Manning 《Molecular imaging and biology》2016,18(1):18-23
Purpose
Alanine-serine-cysteine transporter 2 (ASCT2) expression has been demonstrated as a promising lung cancer biomarker. (2S,4R)-4-[18F]Fluoroglutamine (4-[18F]fluoro-Gln) positron emission tomography (PET) was evaluated in preclinical models of non-small cell lung cancer as a quantitative, non-invasive measure of ASCT2 expression.Procedures
In vivo microPET studies of 4-[18F]fluoro-Gln uptake were undertaken in human cell line xenograft tumor-bearing mice of varying ASCT2 levels, followed by a genetically engineered mouse model of epidermal growth factor receptor (EGFR)-mutant lung cancer. The relationship between a tracer accumulation and ASCT2 levels in tumors was evaluated by IHC and immunoblotting.Result
4-[18F]Fluoro-Gln uptake, but not 2-deoxy-2-[18F]fluoro-D-glucose, correlated with relative ASCT2 levels in xenograft tumors. In genetically engineered mice, 4-[18F]fluoro-Gln accumulation was significantly elevated in lung tumors, relative to normal lung and cardiac tissues.Conclusions
4-[18F]Fluoro-Gln PET appears to provide a non-invasive measure of ASCT2 expression. Given the potential of ASCT2 as a lung cancer biomarker, this and other tracers reflecting ASCT2 levels could emerge as precision imaging diagnostics in this setting.16.
Purpose
Previously, we demonstrated specific accumulation into bacteria of a 12-mer phosphorodiamidate morpholino (MORF) oligomer complementary to a ribosomal RNA (rRNA) segment found in all bacteria using the universal probe called Eub338 (Eub). Here, two MORF oligomers Eco and Kpn with sequences specific to the rRNA of Escherichia coli (Eco) and Klebsiella pneumoniae (Kpn) were investigated along with Eub and control (nonEub).Procedures
To determine bacterial rRNA binding, oligomers were tagged with Alexa Fluor 633 (AF633) for fluorescence in situ hybridization (FISH) and fluorescence microscopy, and radiolabeled with technetium-99m (Tc-99m) for biodistribution and SPECT imaging in infected mice.Results
By both FISH and fluorescence microscopy, Eub showed a positive signal in both E. coli and K. pneumoniae as expected, and Kpn showed significantly higher accumulation in K. pneumoniae with near background in E. coli (p?<?0.01). Conversely, Eco was positive in both E. coli and K. pneumoniae, hence nonspecific. As determined by biodistribution, the accumulation of [99mTc]Kpn was higher in the thigh infected with live K. pneumoniae than with live E. coli (p?=?0.05), and significantly higher than with heat-killed K. pneumoniae (p?=?0.02) in the target thigh. By SPECT imaging, the accumulation of [99mTc]Kpn was obviously higher in its specific target of K. pneumoniae compared to an E. coli infected thigh.Conclusions
Kpn complementary to the rRNA of K. pneumoniae, labeled with Tc-99m or AF633, demonstrated specific binding to fixed and live K. pneumoniae in culture and in infected mice such that Tc-99m-labeled Kpn as the MORF oligomer may be useful for K. pneumoniae infection detection through imaging.17.
Steve S. Cho Ryan Zeh John T. Pierce Ryan Salinas Sunil Singhal John Y. K. Lee 《Molecular imaging and biology》2018,20(2):213-220
Purpose
Distinguishing neoplasm from normal brain parenchyma intraoperatively is critical for the neurosurgeon. 5-Aminolevulinic acid (5-ALA) has been shown to improve gross total resection and progression-free survival but has limited availability in the USA. Near-infrared (NIR) fluorescence has advantages over visible light fluorescence with greater tissue penetration and reduced background fluorescence. In order to prepare for the increasing number of NIR fluorophores that may be used in molecular imaging trials, we chose to compare a state-of-the-art, neurosurgical microscope (System 1) to one of the commercially available NIR visualization platforms (System 2).Procedures
Serial dilutions of indocyanine green (ICG) were imaged with both systems in the same environment. Each system’s sensitivity and dynamic range for NIR fluorescence were documented and analyzed. In addition, brain tumors from six patients were imaged with both systems and analyzed.Results
In vitro, System 2 demonstrated greater ICG sensitivity and detection range (System 1 1.5–251 μg/l versus System 2 0.99–503 μg/l). Similarly, in vivo, System 2 demonstrated signal-to-background ratio (SBR) of 2.6 ± 0.63 before dura opening, 5.0 ± 1.7 after dura opening, and 6.1 ± 1.9 after tumor exposure. In contrast, System 1 could not easily detect ICG fluorescence prior to dura opening with SBR of 1.2 ± 0.15. After the dura was reflected, SBR increased to 1.4 ± 0.19 and upon exposure of the tumor SBR increased to 1.8 ± 0.26.Conclusion
Dedicated NIR imaging platforms can outperform conventional microscopes in intraoperative NIR detection. Future microscopes with improved NIR detection capabilities could enhance the use of NIR fluorescence to detect neoplasm and improve patient outcome.18.
Coralie Germain-Genevois Olivia Garandeau Franck Couillaud 《Molecular imaging and biology》2016,18(1):62-69
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.19.
Heringlake M Handke U Hanke T Eberhardt F Schumacher J Gehring H Heinze H 《Intensive care medicine》2007,33(12):2168-2172
Objective
The modified algorithm for the non-invasive determination of cardiac output (CO) by electrical bioimpedance—electrical velocimetry (EV®)—has been reported to give reliable results in comparison with echocardiography and pulmonary arterial thermodilution (PA-TD) in patients either before or after cardiac surgery. The present study was designed to determine whether EV®-CO measurements reflect intraindividual changes in CO during cardiac surgery.Design
Prospective, observational study.Setting
Operating room (OR) and intensive care unit (ICU) of a university hospital.Patients
Twenty-nine patients undergoing elective cardiac surgery.Interventions
None.Measurements
CO was determined simultaneously by PA-TD and EV® after induction of anesthesia (t1) and 4.9?±?3.5?h after ICU admission (t2).Results
TD-CO was 3.9?±?1.4 and 5.4?±?1.1 l/min at t1 and t2 (?p?0.0001). EV®-CO was 4.3?±?1.1 and 4.9?±?1.5 l/min at t1 and t2 (?p?=?0.013). Bland–Altman analysis showed a bias of ?0.4 l/min and 0.4 l/min and a precision of 3.2 and 3.6 l/min (34.3% and 67.4%) at t1 and t2, respectively. Analysis of the individual pre- to postoperative changes in CO with both methods revealed bidirectional changes in n?=?12 patients and unidirectional changes with a difference greater than 50% and less than 50% in n?=?9 and n?=?8 patients, respectively.Conclusions
The disagreement between PA-TD and EV®-CO measurements after anesthesia induction and after ICU admission, as well as the fact that thoracic bioimpedance did not adequately reflect pre- to postoperative changes in CO, questions the reliability of EV®-CO measurements in cardiac surgery patients and contrasts sharply with previous studies.20.
Amer M. Najjar Pallavi R Manuri Simon Olivares Leo FloresII Tiejuan Mi Helen Huls Elizabeth J. Shpall Richard E. Champlin Nashaat Turkman Vincenzo Paolillo Jason Roszik Brian Rabinovich Dean A. Lee Mian Alauddin Juri Gelovani Laurence J.N. Cooper 《Molecular imaging and biology》2016,18(6):838-848