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1.
Anna Rethy Jørn Ove Sæternes Jostein Halgunset Ronald Mårvik Erlend F. Hofstad Juan A. Sánchez-Margallo Thomas Langø 《International journal of computer assisted radiology and surgery》2018,13(1):61-72
Purpose
The objective of this study was to develop a multimodal, permanent liver phantom displaying functional vasculature and common pathologies, for teaching, training and equipment development in laparoscopic ultrasound and navigation.Methods
Molten wax was injected simultaneously into the portal and hepatic veins of a human liver. Upon solidification of the wax, the surrounding liver tissue was dissolved, leaving a cast of the vessels. A connection was established between the two vascular trees by manually manipulating the wax. The cast was placed, along with different multimodal tumor models, in a liver shaped mold, which was subsequently filled with a polymer. After curing, the wax was melted and flushed out of the model, thereby establishing a system of interconnected channels, replicating the major vasculature of the original liver. Thus, a liquid can be circulated through the model in a way that closely mimics the natural blood flow.Results
Both the tumor models, i.e., the metastatic tumors, hepatocellular carcinoma and benign cyst, and the vessels inside the liver model, were clearly visualized by all the three imaging modalities: CT, MR and ultrasound. Doppler ultrasound images of the vessels proved the blood flow functionality of the phantom.Conclusion
By a two-step casting procedure, we produced a multimodal liver phantom, with open vascular channels, and tumor models, that is the next best thing to practicing imaging and guidance procedures in animals or humans. The technique is in principle applicable to any organ of the body.2.
Jane J. Keating Olugbenga T. Okusanya Elizabeth De Jesus Ryan Judy Jack Jiang Charuhas Deshpande Shuming Nie Philip Low Sunil Singhal 《Molecular imaging and biology》2016,18(2):209-218
Purpose
During lung surgery, identification of surgical margins is challenging. We hypothesized that molecular imaging with a fluorescent probe to pulmonary adenocarcinomas could enhance residual tumor during resection.Procedures
Mice with flank tumors received a contrast agent targeting folate receptor alpha. Optimal dose and time of injection was established. Margin detection was compared using traditional methods versus molecular imaging. A pilot study was then performed in three humans with lung adenocarcinoma.Results
The peak tumor-to-background ratio (TBR) of murine tumors was 3.9. Fluorescence peaked at 2 h and was not improved beyond 0.1 mg/kg. Traditional inspection identified 30 % of mice with positive margins. Molecular imaging identified an additional 50 % of residual tumor deposits (p?<?0.05). The fluorescent probe visually enhanced all human tumors with a mean TBR of 3.5.Conclusions
Molecular imaging is an important adjunct to traditional inspection to identify surgical margins after tumor resection.3.
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.4.
Marta Vilalta Nicholas P Hughes Rie Von Eyben Amato J. Giaccia Edward E. Graves 《Molecular imaging and biology》2017,19(2):215-224
Purpose
Preclinical studies of hypoxia are generally done using ectopic xenograft tumors, which behave differently from human tumors. Our previous findings have shown that subcutaneously implanted lung tumors exhibit more hypoxia than their orthotopic implanted or spontaneous K-ras-induced counterparts. We hypothesize that differences in hypoxia are due to site-specific differences in vascularity and perfusion.Procedures
To compare the presence and functionality of vessels in these tumor models, we studied vascular perfusion in vivo in real time.Results
Orthotopically implanted and spontaneous K-ras-induced lung tumors showed elevated perfusion, demonstrating vasculature functionality. Little contrast agent uptake was observed within the subcutaneously implanted tumors, indicating vascular dysfunction. These findings were corroborated at the microscopic level with Hoechst 33342 and Meca-32 staining.Conclusions
From these observations, we concluded that differences in hypoxia in experimental models is related to vessel perfusion. Thus, appropriate selection of preclinical lung tumor models is essential for the study of hypoxia, angiogenesis and therapies targeting these phenomena.5.
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.6.
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.7.
Yifang Hu Jie Liu Chengcai Leng Yu An Shuang Zhang Kun Wang 《Molecular imaging and biology》2016,18(6):830-837
Purpose
Bioluminescence tomography (BLT) is a promising in vivo optical imaging technique in preclinical research at cellular and molecular levels. The problem of BLT reconstruction is quite ill-posed and ill-conditioned. In order to achieve high accuracy and efficiency for its inverse reconstruction, we proposed a novel approach based on L p regularization with the Split Bregman method.Procedures
The diffusion equation was used as the forward model. Then, we defined the objective function of L p regularization and developed a Split Bregman iteration algorithm to optimize this function. After that, we conducted numerical simulations and in vivo experiments to evaluate the accuracy and efficiency of the proposed method.Results
The results of the simulations indicated that compared with the conjugate gradient and iterative shrinkage methods, the proposed method is more accurate and faster for multisource reconstructions. Furthermore, in vivo imaging suggested that it could clearly distinguish the viable and apoptotic tumor regions.Conclusions
The Split Bregman iteration method is able to minimize the L p regularization problem and achieve fast and accurate reconstruction in BLT.8.
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.9.
Cheng Liu Shiying Li Yanjuan Gu Huahua Xiong Wing-tak Wong Lei Sun 《Molecular imaging and biology》2018,20(6):919-929
Purpose
Tumor proteases have been recognized as significant regulators in the tumor microenvironment, but the current strategies for in vivo protease imaging have tended to focus on the development of a probe design rather than the investigation of a novel imaging strategy by leveraging the imaging technique and probe. Herein, it is the first report to investigate the ability of multispectral photoacoustic imaging (PAI) to estimate the distribution of protease cleavage sites inside living tumor tissue by using an activatable photoacoustic (PA) probe.Procedures
The protease MMP-2 is selected as the target. In this probe, gold nanocages (GNCs) with an absorption peak at ~?800 nm and fluorescent dye molecules with an absorption peak at ~?680 nm are conjugated via a specific enzymatic peptide substrate. Upon enzymatic activation by MMP-2, the peptide substrate is cleaved and the chromophores are released. Due to the different retention speeds of large GNCs and small dye molecules, the probe alters its intrinsic absorption profile and produces a distinct change in the PA signal. A multispectral PAI technique that can distinguish different chromophores based on intrinsic PA spectral signatures is applied to estimate the signal composition changes and indicate the cleavage interaction sites. Finally, the multispectral PAI technique with the activatable probe is tested in solution, cultured cells, and a subcutaneous tumor model in vivo.Results
Our experiment in solution with enzyme ± inhibitor, cell culture ± inhibitor, and in vivo tumor model with administration of the developed probe ± inhibitor demonstrated the probe was cleaved by the targeted enzyme. Particularly, the in vivo estimation of the cleavage site distribution was validated with the result of ex vivo immunohistochemistry analysis.Conclusions
This novel synergy of the multispectral PAI technique and the activatable probe is a potential strategy for the distribution estimation of tumor protease activity in vivo.10.
Carlo Cattaneo Jaime Kulisevsky Viviana Tubazio Paola Castellani 《Advances in therapy》2018,35(4):515-522
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.11.
Susanna W. L. de Geus Leonora S. F. Boogerd Rutger-Jan Swijnenburg J. Sven D. Mieog Willemieke S. F. J. Tummers Hendrica A. J. M. Prevoo Cornelis F. M. Sier Hans Morreau Bert A. Bonsing Cornelis J. H. van de Velde Alexander L. Vahrmeijer Peter J. K. Kuppen 《Molecular imaging and biology》2016,18(6):807-819
Purpose
The purpose of this study was to identify suitable molecular targets for tumor-specific imaging of pancreatic adenocarcinoma.Procedures
The expression of eight potential imaging targets was assessed by the target selection criteria (TASC)—score and immunohistochemical analysis in normal pancreatic tissue (n?=?9), pancreatic (n?=?137), and periampullary (n?=?28) adenocarcinoma.Results
Integrin αvβ6, carcinoembryonic antigen (CEA), epithelial growth factor receptor (EGFR), and urokinase plasminogen activator receptor (uPAR) showed a significantly higher (all p?<?0.001) expression in pancreatic adenocarcinoma compared to normal pancreatic tissue and were confirmed by the TASC score as promising imaging targets. Furthermore, these biomarkers were expressed in respectively 88 %, 71 %, 69 %, and 67 % of the pancreatic adenocarcinoma patients.Conclusions
The results of this study show that integrin αvβ6, CEA, EGFR, and uPAR are suitable targets for tumor-specific imaging of pancreatic adenocarcinoma.12.
Purpose
To retrospectively investigate the utility of diffusion-weighted imaging (DWI) for predicting clinical outcome after concurrent chemoradiotherapy (CCRT) in uterine cervical cancer.Materials and methods
Seventy-four consecutive patients with biopsy-proven cervical cancer who received CCRT underwent DWI at 3T. All patients had MR examinations before therapy (preTx) and at 4 weeks of initiating therapy (midTx). At each point, ADC (apparent diffusion coefficient) was measured in the tumors and ADC change between preTx and midTx were also calculated. For predicting tumor recurrence, MR variables and clinical variables were evaluated and the results were compared.Results
During a mean follow-up of 32.1 months, tumor recurrence developed in 15 (20%) patients: local recurrence (n = 7), distant metastasis (n = 5), and both (n = 3). MidTx tumor ADCs and tumor ADC changes between preTx and midTx were significantly different between the recurrence and non-recurrence groups (P < 0.05), while preTx tumor ADCs were not significantly different between the groups (P = 0.892). Univariate analysis revealed that histologic type, stage, preTx tumor size and volume, and tumor ADC change were significantly related to tumor recurrence (all P < 0.05). However, on multivariate analysis, tumor ADC changes [hazard ratio (HR) 0.886; 95% confidence interval (CI) 0.836–0.940; P = 0.001] and histological type (HR 6.063; 95% CI 1.404–26.187; P = 0.016) were the significant independent predictors of tumor recurrence.Conclusion
Tumor ADC changes between preTx and midTx might be a useful biomarker for the prediction of cervical cancer recurrence after CCRT.13.
Massimiliano Spaliviero Stefan Harmsen Ruimin Huang Matthew A. Wall Chrysafis Andreou James A. Eastham Karim A. Touijer Peter T. Scardino Moritz F. Kircher 《Molecular imaging and biology》2016,18(5):677-685
Purpose
The accurate detection of lymph node metastases in prostate cancer patients is important to direct treatment decisions. Our goal was to develop an intraoperative imaging approach to distinguish normal from metastasized lymph nodes. We aimed at developing and testing gold-silica surface-enhanced resonance Raman spectroscopy (SERRS) nanoparticles that demonstrate high uptake within normal lymphatic tissue and negligible uptake in areas of metastatic replacement.Procedures
We evaluated the ability of SERRS nanoparticles to delineate lymph node metastases in an orthotopic prostate cancer mouse model using PC-3 cells transduced with mCherry fluorescent protein. Tumor-bearing mice (n?=?6) and non-tumor-bearing control animals (n?=?4) were injected intravenously with 30 fmol/g SERRS nanoparticles. After 16–18 h, the retroperitoneal lymph nodes were scanned in situ and ex vivo with a Raman imaging system and a handheld Raman scanner and data corroborated with fluorescence imaging for mCherry protein expression and histology.Results
The SERRS nanoparticles demonstrated avid homing to normal lymph nodes, but not to metastasized lymph nodes. In cases where lymph nodes were partially infiltrated by tumor cells, the SERRS signal correctly identified, with sub-millimeter precision, healthy from metastasized components.Conclusions
This study serves as a first proof-of-principle that SERRS nanoparticles enable high precision and rapid intraoperative discrimination between normal and metastasized lymph nodes.14.
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.15.
Aya Noro Takashi Nakamura Toshiko Hirai Masayo Haga Toyoki Kobayashi Akinobu Hayashi Yuji Kozuka Tokiko Nakai Toru Ogura Tomoko Ogawa 《Journal of Medical Ultrasonics》2016,43(2):227-235
Purpose
To prospectively evaluate the usefulness of contrast-enhanced ultrasound (CEUS) using parametric imaging for breast cancer in a multicenter study.Methods
A total of 65 patients with breast cancer were included in this study. CEUS was performed, and still images on peak time (S), accumulated images (A) and parametric images (P) were generated from the raw data. Four blind reviewers ranked the best visible images as first place, and determined second and third place consecutively. We compared the average ranking of each image. The maximal diameter of the tumor determined on ultrasonography and MRI was compared with the corresponding pathological maximal diameter for 48 of the 65 patients. The correlation between the diameter determined by two experts and two beginners was analyzed.Results
The average rank of visibility was as follows: P, 1.44; A, 2.04; and S, 2.52. The correlation between each image and the pathology was as follows: P, r = 0.664; A, r = 0.630; S, r = 0.717; and MRI, r = 0.936. There were no significant differences among the correlation between the experts and beginners in each image.Conclusions
The use of parametric imaging improves the visibility of CEUS. The maximal diameter of the tumor determined on CEUS correlates substantially with the pathology.16.
Sanhita Sinharay Edward A. Randtke Christine M. Howison Natalia A. Ignatenko Mark D. Pagel 《Molecular imaging and biology》2018,20(2):240-248
Purpose
The detection of enzyme activities and evaluation of enzyme inhibitors have been challenging with magnetic resonance imaging (MRI). To address this need, we have developed a diamagnetic, nonmetallic contrast agent and a protocol known as catalyCEST MRI that uses chemical exchange saturation transfer (CEST) to detect enzyme activity as well as enzyme inhibition.Procedures
We synthesized a diamagnetic MRI contrast agent that has enzyme responsive and enzyme unresponsive CEST signals. We tested the ability of this agent to detect the activity of kallikrein 6 (KLK6) in biochemical solutions, in vitro and in vivo, with and without a KLK6 inhibitor.Results
The agent detected KLK6 activity in solution and also detected KLK6 inhibition by antithrombin III. KLK6 activity was detected during in vitro studies with HCT116 colon cancer cells, relative to the detection of almost no activity in a KLK6-knockdown HCT116 cell line and HCT116 cells treated with antithrombin III inhibitor. Finally, strong enzyme activity was detected within an in vivo HCT116 tumor model, while lower enzyme activity was detected in a KLK6 knockdown tumor model and in the HCT116 tumor model treated with antithrombin III inhibitor. In all cases, comparisons of the enzyme responsive and enzyme unresponsive CEST signals were critical for the detection of enzyme activity.Conclusions
This study has established that catalyCEST MRI with an exogenous diaCEST agent can evaluate enzyme activity and inhibition in solution, in vitro and in vivo.17.
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.18.
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.19.
Sara Rapic Christel Vangestel Jeroen Verhaeghe David Thomae Patrick Pauwels Tim Van den Wyngaert Steven Staelens Sigrid Stroobants 《Molecular imaging and biology》2017,19(1):109-119
Purpose
In oncology, positron emission tomography imaging using dedicated tracers as biomarkers may assist in early evaluation of therapy efficacy. Using 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT), we investigated the early effects of chemotherapeutic treatment on cancer cell proliferation in a BRAF-mutated colorectal cancer xenograft model.Procedures
Colo205 subcutaneously inoculated animals underwent 90-min dynamic imaging before and 24 h after treatment with vehicle (control), cetuximab (resistant) or irinotecan (sensitive). Total distribution volume was quantified from dynamic data, and standardized uptake values as well as tumor-to-blood ratios were calculated from static images averaged over the last 20 min. In vivo imaging data was correlated with ex vivo proliferation and thymidine metabolism proteins.Results
All imaging parameters showed a significant post-treatment decrease from [18F]FLT baseline uptake for the irinotecan group (p?≤?0.001) as compared with the cetuximab and vehicle group and correlated strongly with each other (p?≤?0.0001). In vivo data were in agreement with Ki67 staining, showing a significantly lower percentage of Ki67-positive cells in the irinotecan group as compared with other groups (p?≤?0.0001). Tumor expression of thymidine kinase 1 phosphorylated on serine 13, thymidylate synthase, and thymidine phosphorylase remained unaffected, while thymidine kinase 1 expression was, surprisingly, significantly higher in irinotecan-treated animals (p?≤?0.01). In contrast, tumor ATP levels were lowest in this group.Conclusions
[18F]FLT positron emission tomography was found to be a suitable biomarker of early tumor response to anti-proliferative treatment, with static imaging not being inferior to full compartmental analysis in our xenograft model. The dynamics of thymidine kinase 1 protein expression and protein activity in low ATP environments merits further investigation.20.
Federico Franchi Karen M. Peterson Ramasamy Paulmurugan Clifford Folmes Ian R. Lanza Amir Lerman Martin Rodriguez-Porcel 《Molecular imaging and biology》2016,18(4):510-518