共查询到20条相似文献,搜索用时 25 毫秒
1.
Mette Munk Jensen Kamille Dumong Erichsen Fredrik Bj?rkling Jacob Madsen Peter Buhl Jensen Maxwell Sehested Liselotte H?jgaard Andreas Kj?r 《PloS one》2012,7(11)
Aim
3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT) is a tracer used to assess cell proliferation in vivo. The aim of the study was to use [18F]FLT positron emission tomography (PET) to study non-invasively early anti-proliferative effects of the experimental chemotherapeutic agent TP202377 in both sensitive and resistant tumors.Methods
Xenografts in mice from 3 human cancer cell lines were used: the TP202377 sensitive A2780 ovary cancer cell line (n = 8–16 tumors/group), the induced resistant A2780/Top216 cell line (n = 8–12 tumors/group) and the natural resistant SW620 colon cancer cell line (n = 10 tumors/group). In vivo uptake of [18F]FLT was studied at baseline and repeated 6 hours, Day 1, and Day 6 after TP202377 treatment (40 mg/kg i.v.) was initiated. Tracer uptake was quantified using small animal PET/CT.Results
TP202377 (40 mg/kg at 0 hours) caused growth inhibition at Day 6 in the sensitive A2780 tumor model compared to the control group (P<0.001). In the A2780 tumor model TP202377 treatment caused significant decrease in uptake of [18F]FLT at 6 hours (-46%; P<0.001) and Day 1 (-44%; P<0.001) after treatment start compared to baseline uptake. At Day 6 uptake was comparable to baseline. Treatment with TP202377 did not influence tumor growth or [18F]FLT uptake in the resistant A2780/Top216 and SW620 tumor models. In all control groups uptake of [18F]FLT did not change. Ki67 gene expression paralleled [18F]FLT uptake.Conclusion
Treatment of A2780 xenografts in mice with TP202377 (single dose i.v.) caused a significant decrease in cell proliferation assessed by [18F]FLT PET after 6 hours. Inhibition persisted at Day 1; however, cell proliferation had returned to baseline at Day 6. In the resistant A2780/Top216 and SW620 tumor models uptake of [18F]FLT did not change after treatment. With [18F]FLT PET it was possible to distinguish non-invasively between sensitive and resistant tumors already 6 hours after treatment initiation. 相似文献2.
Matthias Scheffler Thomas Zander Lucia Nogova Carsten Kobe Deniz Kahraman Markus Dietlein Irini Papachristou Lukas Heukamp Reinhard Büttner Ron Boellaard Adriaan A. Lammertsma Silvia Querings Erich Stoelben Walburga Engel-Riedel Bernd Neumaier Jürgen Wolf 《PloS one》2013,8(1)
3′-deoxy-3′-[18F]fluoro-L-thymidine (FLT) and 2′-deoxy-2′-[18F]fluoro-D-glucose (FDG) are used to visualize proliferative and metabolic activity of tumors. In this study we aimed at evaluating the prognostic value of FLT and FDG uptake measured by positron emission tomography (PET) in patients with metastatic non-small cell lung cancer (NSCLC) prior to systemic therapy with erlotinib. FLT and FDG maximum standardized uptake (SUVmax) values per patient were analyzed in 40 chemotherapy naive patients with advanced NSCLC (stage IV) before treatment with erlotinib. Prior therapy median SUVmax was 6.6 for FDG and 3.0 for FLT, respectively. In univariate analysis, patients with an FDG SUVmax <6.6 had a significantly better overall survival (16.3 months [95% confidence interval [CI] 7.1–25.4 months]) compared to patients with an FDG SUVmax ≥6.6 (3.1 months [95% CI 0.6–5.5 months]) (p<0.001, log rank). Similarly, low FLT uptake (SUVmax <3.0) was associated with significantly longer survival (10.3 months (0–23.3 months, 95% CI) compared to high FLT uptake (3.4 months (0–8.1 months, 95% CI) (p = 0.027). The independent prognostic value of baseline FDG uptake was demonstrated in multivariate analysis (p = 0.05, Cox regression). These data suggest that baseline SUVmax values for both FDG and FLT PET might be further developed as markers for prognostic stratification of patients in advanced NSCLC treated with tyrosine kinase inhibitors (TKI) directed against the epidermal growth factor receptor (EGFR).
Trial Registration
Clinicaltrials.gov, Identifier: NCT00568841相似文献3.
Thomas Viel Sonja Schelhaas Stefan Wagner Lydia Wachsmuth Katrin Schwegmann Michael Kuhlmann Cornelius Faber Klaus Kopka Michael Sch?fers Andreas H. Jacobs 《PloS one》2013,8(7)
Addition of temozolomide (TMZ) to radiation therapy is the standard treatment for patients with glioblastoma (GBM). However, there is uncertainty regarding the effectiveness of TMZ. Considering the rapid evolution of the disease, methods to assess TMZ efficacy early during treatment would be of great benefit. Our aim was to monitor early effects of TMZ in a mouse model of GBM using positron emission tomography (PET) with 3′-deoxy-3′-[18F]fluorothymidine ([18F]FLT).
Methods
Human glioma cells sensitive to TMZ (Gli36dEGFR-1) were treated with sub-lethal doses of TMZ to obtain cells with lower sensitivity to TMZ (Gli36dEGFR-2), as measured by growth and clonogenic assays. Gli36dEGFR-1 and Gli36dEGFR-2 cells were subcutaneously (s.c.) or intracranially (i.c.) xenografted into nude mice. Mice were treated for 7 days with daily injection of 25 or 50 mg/kg TMZ. Treatment efficacy was measured using [18F]FLT-PET before treatment and after 2 days. Computed Tomography (CT) or Magnetic Resonance Imaging (MRI) were used to determine tumor volumes before treatment and after 7 days.Results
A significant difference was observed between TMZ and DMSO treated tumors in terms of variations of [18F]FLT T/B ratio as soon as day 2 in the i.c. as well as in the s.c. mouse model. Variations of [18F]FLT T/B uptake ratio between days 0 and 2 correlated with variations of tumor size between days 0 and 7 (s.c. model: ntumor = 17 in nmice = 11, P<0.01; i.c. model: ntumor/mice = 9, P<0.01).Conclusions
Our results indicate that [18F]FLT-PET may be useful for an early evaluation of the response of GBM to TMZ chemotherapy in patients with glioma. 相似文献4.
Martha Nowosielski Matthew D. DiFranco Daniel Putzer Marcel Seiz Wolfgang Recheis Andreas H. Jacobs Günther Stockhammer Markus Hutterer 《PloS one》2014,9(4)
Objectives
Intra-individual spatial overlap analysis of tumor volumes assessed by MRI, the amino acid PET tracer [18F]-FET and the nucleoside PET tracer [18F]-FLT in high-grade gliomas (HGG).Methods
MRI, [18F]-FET and [18F]-FLT PET data sets were retrospectively analyzed in 23 HGG patients. Morphologic tumor volumes on MRI (post-contrast T1 (cT1) and T2 images) were calculated using a semi-automatic image segmentation method. Metabolic tumor volumes for [18F]-FET and [18F]-FLT PETs were determined by image segmentation using a threshold-based volume of interest analysis. After co-registration with MRI the morphologic and metabolic tumor volumes were compared on an intra-individual basis in order to estimate spatial overlaps using the Spearman''s rank correlation coefficient and the Mann-Whitney U test.Results
[18F]-FLT uptake was negative in tumors with no or only moderate contrast enhancement on MRI, detecting only 21 of 23 (91%) HGG. In addition, [18F]-FLT uptake was mainly restricted to cT1 tumor areas on MRI and [18F]-FLT volumes strongly correlated with cT1 volumes (r = 0.841, p<0.001). In contrast, [18F]-FET PET detected 22 of 23 (96%) HGG. [18F]-FET uptake beyond areas of cT1 was found in 61% of cases and [18F]-FET volumes showed only a moderate correlation with cT1 volumes (r = 0.573, p<0.001). Metabolic tumor volumes beyond cT1 tumor areas were significantly larger for [18F]-FET compared to [18F]-FLT tracer uptake (8.3 vs. 2.7 cm3, p<0.001).Conclusion
In HGG [18F]-FET but not [18F]-FLT PET was able to detect metabolic active tumor tissue beyond contrast enhancing tumor on MRI. In contrast to [18F]-FET, blood-brain barrier breakdown seems to be a prerequisite for [18F]-FLT tracer uptake. 相似文献5.
Cindy Casteels Kathleen Vunckx Sarah-Ann Aelvoet Veerle Baekelandt Guy Bormans Koen Van Laere Michel Koole 《PloS one》2013,8(6)
Automated voxel-based or pre-defined volume-of-interest (VOI) analysis of small-animal PET data in mice is necessary for optimal information usage as the number of available resolution elements is limited. We have mapped metabolic ([18F]FDG) and dopamine transporter ([18F]FECT) small-animal PET data onto a 3D Magnetic Resonance Microscopy (MRM) mouse brain template and aligned them in space to the Paxinos co-ordinate system. In this way, ligand-specific templates for sensitive analysis and accurate anatomical localization were created. Next, using a pre-defined VOI approach, test-retest and intersubject variability of various quantification methods were evaluated. Also, the feasibility of mouse brain statistical parametric mapping (SPM) was explored for [18F]FDG and [18F]FECT imaging of 6-hydroxydopamine-lesioned (6-OHDA) mice.
Methods
Twenty-three adult C57BL6 mice were scanned with [18F]FDG and [18F]FECT. Registrations and affine spatial normalizations were performed using SPM8. [18F]FDG data were quantified using (1) an image-derived-input function obtained from the liver (cMRglc), using (2) standardized uptake values (SUVglc) corrected for blood glucose levels and by (3) normalizing counts to the whole-brain uptake. Parametric [18F]FECT binding images were constructed by reference to the cerebellum. Registration accuracy was determined using random simulated misalignments and vectorial mismatch determination.Results
Registration accuracy was between 0.21–1.11 mm. Regional intersubject variabilities of cMRglc ranged from 15.4% to 19.2%, while test-retest values were between 5.0% and 13.0%. For [18F]FECT uptake in the caudate-putamen, these values were 13.0% and 10.3%, respectively. Regional values of cMRglc positively correlated to SUVglc measured within the 45–60 min time frame (spearman r = 0.71). Next, SPM analysis of 6-OHDA-lesioned mice showed hypometabolism in the bilateral caudate-putamen and cerebellum, and an unilateral striatal decrease in DAT availability.Conclusion
MRM-based small-animal PET templates facilitate accurate assessment and spatial localization of mouse brain function using VOI or voxel-based analysis. Regional intersubject- and test-retest variations indicate that for these targets accuracy comparable to humans can be achieved. 相似文献6.
Early detection of response to experimental chemotherapeutic Top216 with [18F]FLT and [18F]FDG PET in human ovary cancer xenografts in mice 总被引:1,自引:0,他引:1
Jensen MM Erichsen KD Björkling F Madsen J Jensen PB Højgaard L Sehested M Kjær A 《PloS one》2010,5(9):e12965
Background
3′-deoxy-3′-[18F]fluorothymidine (18F-FLT) is a tracer used to assess cell proliferation in vivo. The aim of the study was to use 18F-FLT positron emission tomography (PET) to study treatment responses to a new anti-cancer compound. To do so, we studied early anti-proliferative effects of the experimental chemotherapy Top216 non-invasively by PET.Methodology/Principal Findings
In vivo uptake of 18F-FLT in human ovary cancer xenografts in mice (A2780) was studied at various time points after Top216 treatment (50 mg/kg i.v. at 0 and 48 hours) was initiated. Baseline 18F-FLT scans were made before either Top216 (n = 7–10) or vehicle (n = 5–7) was injected and repeated after 2 and 6 hours and 1 and 5 days of treatment. A parallel study was made with 2′-deoxy-2′-[18F]fluoro-D-glucose (18F-FDG) (n = 8). Tracer uptake was quantified using small animal PET/CT. Imaging results were validated by tumor volume changes and gene-expression of Ki67 and TK1. Top216 (50 mg/kg 0 and 48 hours) inhibited the growth of the A2780 tumor compared to the control group (P<0.001). 18F-FLT uptake decreased significantly at 2 hours (−52%; P<0.001), 6 hours (−49%; P = 0.002) and Day 1 (−47%; P<0.001) after Top216 treatment. At Day 5 18F-FLT uptake was comparable to uptake in the control group. Uptake of 18F-FLT was unchanged in the control group during the experiment. In the treatment group, uptake of 18F-FDG was significantly decreased at 6 hours (−21%; P = 0.003), Day 1 (−29%; P<0.001) and Day 5 (−19%; P = 0.05) compared to baseline.Conclusions/Significance
One injection with Top216 initiated a fast and significant decrease in cell-proliferation assessable by 18F-FLT after 2 hours. The early reductions in tumor cell proliferation preceded changes in tumor size. Our data indicate that 18F-FLT PET is promising for the early non-invasive assessment of chemotherapy effects in both drug development and for tailoring therapy in patients. 相似文献7.
Miikka Tarkia Antti Saraste Christoffer Stark Tommi V?h?silta Timo Savunen Marjatta Strandberg Virva Saunavaara Tuula Tolvanen Jarmo Teuho Mika Ter?s Olli Mets?l? Petteri Rinne Ilkka Heinonen Nina Savisto Mikko Pietil? Pekka Saukko Anne Roivainen Juhani Knuuti 《PloS one》2015,10(6)
Objective
Inflammation is an important contributor to atherosclerosis progression. A glucose analogue 18F-fluorodeoxyglucose ([18F]FDG) has been used to detect atherosclerotic inflammation. However, it is not known to what extent [18F]FDG is taken up in different stages of atherosclerosis. We aimed to study the uptake of [18F]FDG to various stages of coronary plaques in a pig model.Methods
First, diabetes was caused by streptozotocin injections (50 mg/kg for 3 days) in farm pigs (n = 10). After 6 months on high-fat diet, pigs underwent dual-gated cardiac PET/CT to measure [18F]FDG uptake in coronary arteries. Coronary segments (n = 33) were harvested for ex vivo measurement of radioactivity and autoradiography (ARG).Results
Intimal thickening was observed in 16 segments and atheroma type plaques in 10 segments. Compared with the normal vessel wall, ARG showed 1.7±0.7 times higher [18F]FDG accumulation in the intimal thickening and 4.1±2.3 times higher in the atheromas (P = 0.004 and P = 0.003, respectively). Ex vivo mean vessel-to-blood ratio was higher in segments with atheroma than those without atherosclerosis (2.6±1.2 vs. 1.3±0.7, P = 0.04). In vivo PET imaging showed the highest target-to-background ratio (TBR) of 2.7. However, maximum TBR was not significantly different in segments without atherosclerosis (1.1±0.5) and either intimal thickening (1.2±0.4, P = 1.0) or atheroma (1.6±0.6, P = 0.4).Conclusions
We found increased uptake of [18F]FDG in coronary atherosclerotic lesions in a pig model. However, uptake in these early stage lesions was not detectable with in vivo PET imaging. Further studies are needed to clarify whether visible [18F]FDG uptake in coronary arteries represents more advanced, highly inflamed plaques. 相似文献8.
Kuo-Lun Huang Kun-Ju Lin Ing-Tsung Hsiao Hung-Chou Kuo Wen-Chuin Hsu Wen-Li Chuang Mei-Ping Kung Shiaw-Pyng Wey Chia-Ju Hsieh Yau-Yau Wai Tzu-Chen Yen Chin-Chang Huang 《PloS one》2013,8(3)
Background
To compare the neocortical amyloid loads among cognitively normal (CN), amnestic mild cognitive impairment (aMCI), and Alzheimer''s disease (AD) subjects with [18F]AV-45 positron emission tomography (PET).Materials and Methods
[18F]AV-45 PET was performed in 11 CN, 13 aMCI, and 12 AD subjects to compare the cerebral cortex-to-whole cerebellum standard uptake value ratios (SUVRs) of global and individual volumes of interest (VOIs) cerebral cortex. The correlation between global cortical [18F]AV-45 SUVRs and Mini-Mental State Examination (MMSE) scores was analyzed.Results
The global cortical [18F]AV-45 SUVRs were significantly different among the CN (1.08±0.08), aMCI (1.27±0.06), and AD groups (1.34±0.13) (p = 0.0003) with amyloidosis positivity rates of 9%, 62%, and 92% in the three groups respectively. Compared to CN subjects, AD subjects had higher SUVRs in the global cortical, precuneus, frontal, parietal, occipital, temporal, and posterior cingulate areas; while aMCI subjects had higher values in the global cortical, precuneus, frontal, occipital and posterior cingulate areas. There were negative correlations of MMSE scores with SUVRs in the global cortical, precuneus, frontal, parietal, occipital, temporal, posterior cingulate and anterior cingulate areas on a combined subject pool of the three groups after age and education attainment adjustment.Conclusions
Amyloid deposition occurs relatively early in precuneus, frontal and posterior cingulate in aMCI subjects. Higher [18F]AV-45 accumulation is present in parietal, occipital and temporal gyri in AD subjects compared to the aMCI group. Significant correlation between MMSE scores and [18F]AV-45 SUVRs can be observed among CN, aMCI and AD subjects. 相似文献9.
Roland T. Ullrich Thomas Zander Bernd Neumaier Mirjam Koker Takeshi Shimamura Yannic Waerzeggers Christa L. Borgman Samir Tawadros Hongfeng Li Martin L. Sos Heiko Backes Geoffrey I. Shapiro Jürgen Wolf Andreas H. Jacobs Roman K. Thomas Alexandra Winkeler 《PloS one》2008,3(12)
Background
Inhibition of the epidermal growth factor receptor (EGFR) has shown clinical success in patients with advanced non-small cell lung cancer (NSCLC). Somatic mutations of EGFR were found in lung adenocarcinoma that lead to exquisite dependency on EGFR signaling; thus patients with EGFR-mutant tumors are at high chance of response to EGFR inhibitors. However, imaging approaches affording early identification of tumor response in EGFR-dependent carcinomas have so far been lacking.Methodology/Principal Findings
We performed a systematic comparison of 3′-Deoxy-3′-[18F]-fluoro-L-thymidine ([18F]FLT) and 2-[18F]-fluoro-2-deoxy-D-glucose ([18F]FDG) positron emission tomography (PET) for their potential to identify response to EGFR inhibitors in a model of EGFR-dependent lung cancer early after treatment initiation. While erlotinib-sensitive tumors exhibited a striking and reproducible decrease in [18F]FLT uptake after only two days of treatment, [18F]FDG PET based imaging revealed no consistent reduction in tumor glucose uptake. In sensitive tumors, a decrease in [18F]FLT PET but not [18F]FDG PET uptake correlated with cell cycle arrest and induction of apoptosis. The reduction in [18F]FLT PET signal at day 2 translated into dramatic tumor shrinkage four days later. Furthermore, the specificity of our results is confirmed by the complete lack of [18F]FLT PET response of tumors expressing the T790M erlotinib resistance mutation of EGFR.Conclusions
[18F]FLT PET enables robust identification of erlotinib response in EGFR-dependent tumors at a very early stage. [18F]FLT PET imaging may represent an appropriate method for early prediction of response to EGFR TKI treatment in patients with NSCLC. 相似文献10.
Hervé Boutin Christian Prenant Renaud Maroy James Galea Andrew D. Greenhalgh Alison Smigova Christopher Cawthorne Peter Julyan Shane M. Wilkinson Samuel D. Banister Gavin Brown Karl Herholz Michael Kassiou Nancy J. Rothwell 《PloS one》2013,8(2)
Purpose
Neuroinflammation is involved in several brain disorders and can be monitored through expression of the translocator protein 18 kDa (TSPO) on activated microglia. In recent years, several new PET radioligands for TSPO have been evaluated in disease models. [18F]DPA-714 is a TSPO radiotracer with great promise; however results vary between different experimental models of neuroinflammation. To further examine the potential of [18F]DPA-714, it was compared directly to [11C]PK11195 in experimental cerebral ischaemia in rats.Methods
Under anaesthesia, the middle cerebral artery of adult rats was occluded for 60 min using the filament model. Rats were allowed recovery for 5 to 7 days before one hour dynamic PET scans with [11C]PK11195 and/or [18F]DPA-714 under anaesthesia.Results
Uptake of [11C]PK11195 vs [18F]DPA-714 in the ischemic lesion was similar (core/contralateral ratio: 2.84±0.67 vs 2.28±0.34 respectively), but severity of the brain ischemia and hence ligand uptake in the lesion appeared to vary greatly between animals scanned with [11C]PK11195 or with [18F]DPA-714. To solve this issue of inter-individual variability, we performed a direct comparison of [11C]PK11195 and [18F]DPA-714 by scanning the same animals sequentially with both tracers within 24 h. In this direct comparison, the core/contralateral ratio (3.35±1.21 vs 4.66±2.50 for [11C]PK11195 vs [18F]DPA-714 respectively) showed a significantly better signal-to-noise ratio (1.6 (1.3–1.9, 95%CI) fold by linear regression) for [18F]DPA-714.Conclusions
In a clinically relevant model of neuroinflammation, uptake for both radiotracers appeared to be similar at first, but a high variability was observed in our model. Therefore, to truly compare tracers in such models, we performed scans with both tracers in the same animals. By doing so, our result demonstrated that [18F]DPA-714 displayed a higher signal-to-noise ratio than [11C]PK11195. Our results suggest that, with the longer half-life of [18F] which facilitates distribution of the tracer across PET centre, [18F]DPA-714 is a good alternative for TSPO imaging. 相似文献11.
12.
Leo Garcia Flores Susanna Bertolini Hsin Hsin Yeh Daniel Young Uday Mukhopadhyay Ashutosh Pal Yunming Ying Andrei Volgin Aleksandr Shavrin Suren Soghomonyan William Tong William Bornmann Mian M. Alauddin Craig Logsdon Juri G. Gelovani 《PloS one》2009,4(11)
Background
Early diagnosis of pancreatic carcinoma with highly sensitive diagnostic imaging methods could save lives of many thousands of patients, because early detection increases resectability and survival rates. Current non-invasive diagnostic imaging techniques have inadequate resolution and sensitivity for detection of small size (∼2–3 mm) early pancreatic carcinoma lesions. Therefore, we have assessed the efficacy of positron emission tomography and computer tomography (PET/CT) imaging with β-O-D-galactopyranosyl-(1,4′)-2′-deoxy-2′-[18F]fluoroethyl-D-glucopyranose ([18F]FEDL) for detection of less than 3 mm orthotopic xenografts of L3.6pl pancreatic carcinomas in mice. [18F]FEDL is a novel radioligand of hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP), which is overexpressed in peritumoral pancreatic acinar cells.Methodology/Principal Findings
Dynamic PET/CT imaging demonstrated rapid accumulation of [18F]FEDL in peritumoral pancreatic tissue (4.04±2.06%ID/g), bi-exponential blood clearance with half-lives of 1.65±0.50 min and 14.14±3.60 min, and rapid elimination from other organs and tissues, predominantly by renal clearance. Using model-independent graphical analysis of dynamic PET data, the average distribution volume ratio (DVR) for [18F]FEDL in peritumoral pancreatic tissue was estimated as 3.57±0.60 and 0.94±0.72 in sham-operated control pancreas. Comparative analysis of quantitative autoradiographic images and densitometry of immunohistochemically stained and co-registered adjacent tissue sections demonstrated a strong linear correlation between the magnitude of [18F]FEDL binding and HIP/PAP expression in corresponding regions (r = 0.88). The in situ analysis demonstrated that at least a 2–4 fold apparent lesion size amplification was achieved for submillimeter tumors and to nearly half a murine pancreas for tumors larger than 3 mm.Conclusion/Significance
We have demonstrated the feasibility of detection of early pancreatic tumors by non-invasive imaging with [18F]FEDL PET/CT of tumor biomarker HIP/PAP over-expressed in peritumoral pancreatic tissue. Non-invasive non-invasive detection of early pancreatic carcinomas with [18F]FEDL PET/CT imaging should aid the guidance of biopsies and additional imaging procedures, facilitate the resectability and improve the overall prognosis. 相似文献13.
Lucy Vivash Marie-Claude Gregoire Viviane Bouilleret Alexis Berard Catriona Wimberley David Binns Peter Roselt Andrew Katsifis Damian E. Myers Rodney J. Hicks Terence J. O'Brien Stefanie Dedeurwaerdere 《PloS one》2014,9(1)
Purpose
Imbalance of inhibitory GABAergic neurotransmission has been proposed to play a role in the pathogenesis of temporal lobe epilepsy (TLE). This study aimed to investigate whether [18F]-flumazenil ([18F]-FMZ) PET could be used to non-invasively characterise GABAA/central benzodiazepine receptor (GABAA/cBZR) density and affinity in vivo in the post-kainic acid status epilepticus (SE) model of TLE.Methods
Dynamic [18F]-FMZ -PET scans using a multi-injection protocol were acquired in four male wistar rats for validation of the partial saturation model (PSM). SE was induced in eight male Wistar rats (10 weeks of age) by i.p. injection of kainic acid (7.5–25 mg/kg), while control rats (n = 7) received saline injections. Five weeks post-SE, an anatomic MRI scan was acquired and the following week an [18F]-FMZ PET scan (3.6–4.6 nmol). The PET data was co-registered to the MRI and regions of interest drawn on the MRI for selected structures. A PSM was used to derive receptor density and apparent affinity from the [18F]-FMZ PET data.Key Findings
The PSM was found to adequately model [18F]-FMZ binding in vivo. There was a significant decrease in hippocampal receptor density in the SE group (p<0.01), accompanied by an increase in apparent affinity (p<0.05) compared to controls. No change in cortical receptor binding was observed. Hippocampal volume reduction and cell loss was only seen in a subset of animals. Histological assessment of hippocampal cell loss was significantly correlated with hippocampal volume measured by MRI (p<0.05), but did not correlate with [18F]-FMZ binding.Significance
Alterations to hippocampal GABAA/cBZR density and affinity in the post-kainic acid SE model of TLE are detectable in vivo with [18F]-FMZ PET and a PSM. These changes are independent from hippocampal cell and volume loss. [18F]-FMZ PET is useful for investigating the role that changes GABAA/cBZR density and binding affinity play in the pathogenesis of TLE. 相似文献14.
Eliot T. McKinley Gregory D. Ayers R. Adam Smith Samir A. Saleh Ping Zhao Mary Kay Washington Robert J. Coffey H. Charles Manning 《PloS one》2013,8(3)
Background
Non-invasive imaging biomarkers of cellular proliferation hold great promise for quantifying response to personalized medicine in oncology. An emerging approach to assess tumor proliferation utilizes the positron emission tomography (PET) tracer 3’-deoxy-3’[18F]-fluorothymidine, [18F]-FLT. Though several studies have associated serial changes in [18F]-FLT-PET with elements of therapeutic response, the degree to which [18F]-FLT-PET quantitatively reflects proliferative index has been continuously debated for more that a decade. The goal of this study was to elucidate quantitative relationships between [18F]-FLT-PET and cellular metrics of proliferation in treatment naïve human cell line xenografts commonly employed in cancer research.Methods and Findings
[18F]-FLT-PET was conducted in human cancer xenograft-bearing mice. Quantitative relationships between PET, thymidine kinase 1 (TK1) protein levels and immunostaining for proliferation markers (Ki67, TK1, PCNA) were evaluated using imaging-matched tumor specimens. Overall, we determined that [18F]-FLT-PET reflects TK1 protein levels, yet the cell cycle specificity of TK1 expression and the extent to which tumors utilize thymidine salvage for DNA synthesis decouple [18F]-FLT-PET data from standard estimates of proliferative index.Conclusions
Our findings illustrate that [18F]-FLT-PET reflects tumor proliferation as a function of thymidine salvage pathway utilization. Unlike more general proliferation markers, such as Ki67, [18F]-FLT PET reflects proliferative indices to variable and potentially unreliable extents. [18F]-FLT-PET cannot discriminate moderately proliferative, thymidine salvage-driven tumors from those of high proliferative index that rely primarily upon de novo thymidine synthesis. Accordingly, the magnitude of [18F]-FLT uptake should not be considered a surrogate of proliferative index. These data rationalize the diversity of [18F]-FLT-PET correlative results previously reported and suggest future best-practices when [18F]-FLT-PET is employed in oncology. 相似文献15.
Liyong Wu Jared Rowley Sara Mohades Antoine Leuzy Marina Tedeschi Dauar Monica Shin Vladimir Fonov Jianping Jia Serge Gauthier Pedro Rosa-Neto the Alzheimer’s Disease Neuroimaging Initiative 《PloS one》2012,7(10)
Background
The hypothetical model of dynamic biomarkers for Alzheimer’s disease (AD) describes high amyloid deposition and hypometabolism at the mild cognitive impairment (MCI) stage. However, it remains unknown whether brain amyloidosis and hypometabolism follow the same trajectories in MCI individuals. We used the concept of early MCI (EMCI) and late MCI (LMCI) as defined by the Alzheimer’s disease Neuroimaging Initiative (ADNI)-Go in order to compare the biomarker profile between EMCI and LMCI.Objectives
To examine the global and voxel-based neocortical amyloid burden and metabolism among individuals who are cognitively normal (CN), as well as those with EMCI, LMCI and mild AD.Methods
In the present study, 354 participants, including CN (n = 109), EMCI (n = 157), LMCI (n = 39) and AD (n = 49), were enrolled between September 2009 and November 2011 through ADNI-GO and ADNI-2. Brain amyloid load and metabolism were estimated using [18F]AV45 and [18F]fluorodeoxyglucose ([18F]FDG) PET, respectively. Uptake ratio images of [18F]AV45 and [18F]FDG were calculated by dividing the summed PET image by the median counts of the grey matter of the cerebellum and pons, respectively. Group differences of global [18F]AV45 and [18F]FDG were analyzed using ANOVA, while the voxel-based group differences were estimated using statistic parametric mapping (SPM).Results
EMCI patients showed higher global [18F]AV45 retention compared to CN and lower uptake compared to LMCI. SPM detected higher [18F]AV45 uptake in EMCI compared to CN in the precuneus, posterior cingulate, medial and dorsal lateral prefrontal cortices, bilaterally. EMCI showed lower [18F]AV45 retention than LMCI in the superior temporal, inferior parietal, as well as dorsal lateral prefrontal cortices, bilaterally. Regarding to the global [18F]FDG, EMCI patients showed no significant difference from CN and a higher uptake ratio compared to LMCI. At the voxel level, EMCI showed higher metabolism in precuneus, hippocampus, entorhinal and inferior parietal cortices, as compared to LMCI.Conclusions
The present results indicate that brain metabolism remains normal despite the presence of significant amyloid accumulation in EMCI. These results suggest a role for anti-amyloid interventions in EMCI aiming to delay or halt the deposition of amyloid and related metabolism impairment. 相似文献16.
Benjamin Kl?sner Niels Buchmann Jens Gempt Florian Ringel Constantin Lapa Bernd Joachim Krause 《PloS one》2015,10(10)
Background
The precise definition of the post-operative resection status in high-grade gliomas (HGG) is crucial for further management. We aimed to assess the feasibility of assessment of the resection status with early post-operative positron emission tomography (PET) using [18F]O-(2-[18F]-fluoroethyl)-L-tyrosine ([18F]FET).Methods
25 patients with the suspicion of primary HGG were enrolled. All patients underwent pre-operative [18F]FET-PET and magnetic resonance imaging (MRI). Intra-operatively, resection status was assessed using 5-aminolevulinic acid (5-ALA). Imaging was repeated within 72h after neurosurgery. Post-operative [18F]FET-PET was compared with MRI, intra-operative assessment and clinical follow-up.Results
[18F]FET-PET, MRI and intra-operative assessment consistently revealed complete resection in 12/25 (48%) patients and incomplete resection in 6/25 cases (24%). In 7 patients, PET revealed discordant findings. One patient was re-resected. 3/7 experienced tumor recurrence, 3/7 died shortly after brain surgery.Conclusion
Early assessment of the resection status in HGG with [18F]FET-PET seems to be feasible. 相似文献17.
Jakub Toczek Alexis Broisat Pascale Perret Marie-Dominique Desruet Daniel Fagret Laurent M. Riou Catherine Ghezzi 《PloS one》2014,9(7)
Background
[18F]-fluorodeoxyglucose (FDG) has been suggested for the clinical and experimental imaging of inflammatory atherosclerotic lesions. Significant FDG uptake in brown adipose tissue (BAT) has been observed both in humans and mice. The objective of the present study was to investigate the influence of periaortic BAT on apolipoprotein E-deficient (apoE−/−) mouse atherosclerotic lesion imaging with FDG.Methods
ApoE−/− mice (36±2 weeks-old) were injected with FDG (12±2 MBq). Control animals (Group A, n = 7) were injected conscious and kept awake at room temperature (24°C) throughout the accumulation period. In order to minimize tracer activity in periaortic BAT, Group B (n = 7) and C (n = 6) animals were injected under anaesthesia at 37°C and Group C animals were additionally pre-treated with propranolol. PET/CT acquisitions were performed prior to animal euthanasia and ex vivo analysis of FDG biodistribution.Results
Autoradiographic imaging indicated higher FDG uptake in atherosclerotic lesions than in the normal aortic wall (all groups, P<0.05) and the blood (all groups, P<0.01) which correlated with macrophage infiltration (R = 0.47; P<0.001). However, periaortic BAT uptake was either significantly higher (Group A, P<0.05) or similar (Group B and C, P = NS) to that observed in atherosclerotic lesions and was shown to correlate with in vivo quantified aortic FDG activity.Conclusion
Periaortic BAT FDG uptake was identified as a confounding factor while using FDG for the non-invasive imaging of mouse atherosclerotic lesions. 相似文献18.
Akiko Hatori Joji Yui Tomoteru Yamasaki Lin Xie Katsushi Kumata Masayuki Fujinaga Yuichiro Yoshida Masanao Ogawa Nobuki Nengaki Kazunori Kawamura Toshimitsu Fukumura Ming-Rong Zhang 《PloS one》2012,7(9)
Purpose
The translocator protein (18 kDa) (TSPO) is highly expressed on the bronchial and bronchiole epithelium, submucosal glands in intrapulmonary bronchi, pneumocytes and alveolar macrophages in human lung. This study aimed to perform positron emission tomography (PET) imaging of lung inflammation with [18F]FEDAC, a specific TSPO radioligand, and to determine cellular sources enriching TSPO expression in the lung.Methods
An acute lung injury model was prepared by intratracheal administration of lipopolysaccharide (LPS) to rat. Uptake of radioactivity in the rat lungs was measured with small-animal PET after injection of [18F]FEDAC. Presence of TSPO was examined in the lung tissue using Western blot and immunohistochemical assays.Results
The uptake of [18F]FEDAC increased in the lung with the progress of inflammation by treatment with LPS. Pretreatment with a TSPO-selective ligand PK11195 showed a significant decrease in the lung uptake of [18F]FEDAC due to competitive binding to TSPO. TSPO expression was elevated in the inflamed lung section and its level responded to the [18F]FEDAC uptake and severity of inflammation. Increase of TSPO expression was mainly found in the neutrophils and macrophages of inflamed lungs.Conclusion
From this study we conclude that PET with [18F]FEDAC may be a useful tool for imaging TSPO expression and evaluating progress of lung inflammation. Study on human lung using [18F]FEDAC-PET is promising. 相似文献19.
Sung Gwe Ahn Minkyung Lee Tae Joo Jeon Kyunghwa Han Hak Min Lee Seung Ah Lee Young Hoon Ryu Eun Ju Son Joon Jeong 《PloS one》2014,9(8)
Background
Patients with hormone receptor-positive breast cancer typically show favorable survival. However, identifying individuals at high risk of recurrence among these patients is a crucial issue. We tested the hypothesis that [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) scans can help predict prognosis in patients with hormone receptor-positive breast cancer.Methods
Between April 2004 and December 2008, 305 patients with hormone receptor-positive breast cancer who underwent FGD-PET were enrolled. Patients with luminal B subtype were identified by positivity for human epidermal growth factor receptor-2 (HER2) or high Ki67 (≥14%) according to criteria recently recommended by the St. Gallen panelists. The cut-off value of SUVmax was defined using the time-dependent receiver operator characteristic curve for recurrence-free survival (RFS).Results
At a median follow up of 6.23 years, continuous SUVmax was a significant prognostic factor with a hazard ratio (HR) of 1.21 (p = 0.021). The cut-off value of SUVmax was defined as 4. Patients with luminal B subtype (n = 82) or high SUVmax (n = 107) showed a reduced RFS (p = 0.031 and 0.002, respectively). In multivariate analysis for RFS, SUVmax carried independent prognostic significance (p = 0.012) whereas classification with immunohistochemical markers did not (p = 0.274). The Harell c-index was 0.729. High SUVmax was significantly associated with larger tumor size, positive nodes, HER2 positivity, high Ki67 (≥14%), high tumor grade, and luminal B subtype.Conclusions
Among patients with hormone receptor-positive breast cancer, FDG-PET can help discriminate patients at high risk of tumor relapse. 相似文献20.
Paolo Zanotti-Fregonara Jussi Hirvonen Chul Hyoung Lyoo Sami S. Zoghbi Denise Rallis-Frutos Marilyn A. Huestis Cheryl Morse Victor W. Pike Robert B. Innis 《PloS one》2013,8(4)