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Jiachuan Wang,
Fangfang Chao,
Feng Han,
Gensheng Zhang,
Qunying Xi,
Jinhui Li,
Han Jiang,
Jing Wang,
Gang Yu,
Mei Tian, Hong Zhang
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ABSTRACT: The purpose of this study was to determine the functionality of the transplanted induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) in a rat model of cerebral ischemia with use of (18)F-FDG small-animal PET imaging. METHODS: Middle cerebral artery occlusion was used to establish cerebral ischemia. Twenty-four male rats were randomly assigned to 1 of 3 groups: iPSC treatment, ESC treatment, and the control phosphate-buffered saline (PBS) injection. After neurologic function tests and baseline (18)F-FDG small-animal PET had been performed, 1.0 × 10(6) suspended iPSCs or ESCs were injected stereotactically into the left lateral ventricle. The treatment response was evaluated weekly by (18)F-FDG PET scans and neurologic function tests. Histologic analyses and autoradiographic imaging were performed 4 wk after stem cell transplantation. RESULTS: Compared with the PBS injection group, higher (18)F-FDG accumulation in the ipsilateral cerebral infarction was observed in both the iPSC and the ESC treatment groups during the 4-wk period (P < 0.05). (18)F-FDG accumulation in the ipsilateral cerebral infarction increased steadily over time in the iPSC treatment group. At 1 and 2 wk after stem cell transplantation, significant recovery of glucose metabolism was found in the ESC treatment group (P < 0.05) and then decreased gradually. The neurologic score in both stem cell-treated groups was significantly lower than that in the PBS group, indicating functional improvement. Immunohistochemical analysis demonstrated that transplanted stem cells survived and migrated close to the ischemic region, and most of the stem cells expressed protein markers for cells of interest. CONCLUSION: (18)F-FDG small-animal PET demonstrated metabolic recovery after iPSC and ESC transplantation in the rat model of cerebral ischemia. iPSCs could be considered a potentially better therapeutic approach than ESCs and are worthy of further translational investigation.
Journal of Nuclear Medicine 03/2013; · 6.38 Impact Factor
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ABSTRACT: Frightening music can rapidly arouse emotions in listeners that mimic those from actual life-threatening experiences. However, studies of the underlying mechanism for perceiving danger created by music are limited.
We investigated monoamine receptor changes induced by frightening music using (11)C-N-methyl-spiperone ((11)C-NMSP) PET. Ten healthy male volunteers were included, and their psychophysiologic changes were evaluated.
Compared with the baseline condition, listening to frightening music caused a significant decrease in (11)C-NMSP in the right and left caudate nuclei, right limbic region, and right paralimbic region; a particularly significant decrease in the right anterior cingulate cortex; but an increase in the right frontal occipital and left temporal lobes of the cerebral cortex.
Transient fright triggers rapid changes in monoamine receptors, which decrease in the limbic and paralimbic regions but increase in the cerebral cortex.
Journal of Nuclear Medicine 08/2012; 53(10):1573-8. · 6.38 Impact Factor
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ABSTRACT: The purpose of this study was to investigate the detectability of small hot lesions with the 3-dimensional transmission/emission
(3D T/E) acquisition mode in FDG-PET scan. The correlation of target detectability, target size, target to non-target uptake
ratio (T/N ratio) and standardized uptake value (SUV) were studied. Small hot lesions ranged from 4.4 mm to 36.9 mm in diameter
were located in cylindrical phantom. The images of phantoms with a T/N ratio of 2.0, 4.0, 6.0, 8.0, 9.6, 13.2, 17.5, 23.8
and 30.3 were obtained with 2-dimensional transmission/emission (2D T/E) scan and 3D T/E scans. Targets in diameter more than
10.6 mm in diameter with an actual T/N ratio ranged from 6.0 to 30.3 could be identified on the images obtained with all the
2D T/E and 3D T/E acquisition modes. The detectability efficiency of small hot target in 2D T/E and 3D T/E scans was as same
(77.8%). The T/N ratio of targets from 2D T/E images was 30% to 48.4% different to that from 3D T/E image, and the SUV of
the target from the 2D T/E images was almost the same as that from 3D T/E images. This study revealed that 3D T/E scanning
had similar hot spot detectability to 2D T/E scanning; 3D T/E and 2D T/E scanning had the same faculty for semiquantitative
analysis using SUV. These findings may be helpful for the diagnosis and understanding of 3D T/E FDG-PET in hot lesion detection.
Annals of Nuclear Medicine 04/2012; 14(4):279-284. · 1.50 Impact Factor
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ABSTRACT: Multiple benign osteolytic lesions are very hard to differentiate from disseminated bone metastasis. Whole-body bone scintigraphy (WBBS) with technetium-99m methylene diphosphonate (Tc-99m MDP) demonstrates multiple lesions with increased uptake in any bone involved. Even combined with medical history and multiple imaging results, such as MRI and CT, the clinical diagnosis of metastasis lesion remains as a challenge. These clinical characteristics are similar to multiple malignant bone metastases and therefore affect the following treatment procedures. In this paper, we analyzed multiple benign osteolytic lesions, like eosinophilic granuloma (EG), multiple myeloma (MM), disseminated tuberculosis, fibrous dysplasia, or enchondroma, occurring in our daily clinical work and concluded that additional attention should be paid before giving the diagnosis of multiple bone metastases.
Journal of Biomedicine and Biotechnology 01/2012; 2012:957364. · 2.44 Impact Factor
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ABSTRACT: Generation of too many reactive oxygen species (ROS) in relation to available antioxidants in living cells can cause oxidative stress, which is involved in the development and progression of several serious diseases. 2',7'-Dichlorodihydrofluorescein (DCFH) and its diacetate form, DCFH-DA, are widely used probes for monitoring general oxidative stress in cells, but DCFH oxidation is not always related to ROS. We report here a new method for quantifying cellular oxidative stress using a 2,2,6,6-tetramethyl- piperidine-1-oxyl (TEMPO)-based probe. We tested and verified the probe both in cell-free solutions and in living cells under conditions of increased or reduced oxidative stress. The probe revealed the oxidative stress status in living cells and may be a useful complement to DCFH fluorescent probes.
The Analyst 08/2011; 136(20):4316-20. · 4.23 Impact Factor
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ABSTRACT: Mood disorders are chronic, recurrent psychiatric disorders with high morbidity rates that cause severe disability. Researchers have used molecular imaging extensively in studies of mood disorders. In this article, we concisely and selectively review the major findings of positron emission tomography studies of patients with mood disorders. Specifically, we describe findings from cerebral blood flow, cerebral glucose/oxygen metabolism, and radioligand studies in both cross-sectional and longitudinal investigations. Patients with mood disorders have mood-correlated regional metabolism changes and molecular abnormalities in several neurotransmitter systems. Although the findings of these studies are not completely consistent and confounding factors, including drug effects and specific methodology, should be strictly controlled, these results reveal the pathophysiology of mood disorders and aid the development of novel treatment approaches for mood disorders. Future positron emission tomography research will benefit greatly from the development of better radioligands to simultaneously identify multiple neurotransmitter systems in the specific brain region and the integration of more detecting methods in specifying the neurobiological predictors of treatment response in patients with mood disorders. Understanding the molecular mechanisms in underlying mood disorders will result in aetiological diagnosis and individualization of treatment of these disorders.
European Journal of Nuclear Medicine 07/2011; 38(7):1367-80. · 4.53 Impact Factor
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ABSTRACT: Human neurological diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, spinal cord injury and multiple sclerosis are caused by loss of different types of neurons and glial cells in the brain and spinal cord. At present, there are no effective therapies against these disorders. Discovery of the therapeutic potential of stem cells offers new strategies for the treatment of neurological diseases. Direct assessment of stem cells' survival, interaction with the host and impact on neuronal functions after transplantation requires advanced in vivo imaging techniques. Positron emission tomography (PET) is a potential molecular imaging modality to evaluate the viability and function of transplanted tissue or stem cells in the nervous system. This review focuses on PET molecular imaging in stem cell therapy for neurological diseases.
European Journal of Nuclear Medicine 06/2011; 38(10):1926-38. · 4.53 Impact Factor
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ABSTRACT: Traditional Chinese medicine (TCM), which is fundamentally different from Western medicine, has been widely investigated using various approaches. Cellular- or molecular-based imaging has been used to investigate and illuminate the various challenges identified and progress made using therapeutic methods in TCM. Insight into the processes of TCM at the cellular and molecular changes and the ability to image these processes will enhance our understanding of various diseases of TCM and will provide new tools to diagnose and treat patients.
Various TCM therapies including herbs and formulations, acupuncture and moxibustion, massage, Gua Sha, and diet therapy have been analyzed using positron emission tomography, single photon emission computed tomography, functional magnetic resonance imaging and ultrasound and optical imaging. These imaging tools have kept pace with developments in molecular biology, nuclear medicine, and computer technology.
We provide an overview of recent developments in demystifying ancient knowledge - like the power of energy flow and blood flow meridians, and serial naturopathies - which are essential to visually and vividly recognize the body using modern technology.
In TCM, treatment can be individualized in a holistic or systematic view that is consistent with molecular imaging technologies. Future studies might include using molecular imaging in conjunction with TCM to easily diagnose or monitor patients naturally and noninvasively.
Journal of ethnopharmacology 06/2011; 137(1):16-26. · 2.32 Impact Factor
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ABSTRACT: One of the major obstacles of the clinical translation of (18)F-labeled arginine-glycine-aspartic acid (RGD) peptides has been the laborious multistep radiosynthesis. In order to facilitate the application of RGD-based positron emission tomography (PET) probes in the clinical setting we investigated in this study the feasibility of using the chelation reaction between Al(18)F and a macrocyclic chelator-conjugated dimeric RGD peptide as a simple one-step (18)F labeling strategy for development of a PET probe for tumor angiogenesis imaging.
Dimeric cyclic peptide E[c(RGDyK)](2) (RGD(2)) was first conjugated with a macrocyclic chelator, 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), and the resulting bioconjugate NOTA-RGD(2) was then radiofluorinated via Al(18)F intermediate to synthesize (18)F-AlF-NOTA-RGD(2). Integrin binding affinities of the peptides were assessed by a U87MG cell-based receptor binding assay using (125)I-echistatin as the radioligand. The tumor targeting efficacy and in vivo profile of (18)F-AlF-NOTA-RGD(2) were further evaluated in a subcutaneous U87MG glioblastoma xenograft model by microPET and biodistribution.
NOTA-RGD(2) was successfully (18)F-fluorinated with good yield within 40 min using the Al(18)F intermediate. The IC(50) of (19)F-AlF-NOTA-RGD(2) was determined to be 46 ± 4.4 nM. Quantitative microPET studies demonstrated that (18)F-AlF-NOTA-RGD(2) showed high tumor uptake, fast clearance from the body, and good tumor to normal organ ratios.
NOTA-RGD(2) bioconjugate has been successfully prepared and labeled with Al(18)F in one single step of radiosynthesis. The favorable in vivo performance and the short radiosynthetic route of (18)F-AlF-NOTA-RGD(2) warrant further optimization of the probe and the radiofluorination strategy to accelerate the clinical translation of (18)F-labeled RGD peptides.
European Journal of Nuclear Medicine 05/2011; 38(9):1732-41. · 4.53 Impact Factor
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ABSTRACT: ¹¹C-choline and ¹⁸F-FAMT are known to correlate with tumor cell proliferation and amino acid metabolism. We investigated the ability of ¹¹C-Choline and ¹⁸F-FAMT PET in diagnosis of musculoskeletal tumors in thirty-six patients in comparison of ¹⁸F-FDG PET. ¹¹C-Choline and ¹⁸F-FDG PET were positive in all the malignant tumors (n = 13), whereas ¹⁸F-FAMT was positive in 11 tumors. The mean SUVs for malignant tumors were significantly higher than those for benign lesions in all three tracers imaging. A moderate correlation was found between ¹¹C-Choline and ¹⁸F-FDG (r = 0.540, P < .05), or ¹⁸F-FAMT and FDG (r = 0.596, P < .05). The diagnostic sensitivity and specificity for malignancy were 91.7% and 71.4%, respectively, using ¹¹C-choline with a SUV cut-off of 2.69. The sensitivity and specificity of ¹⁸F-FAMT for malignancy were 66.7% and 85.7%, respectively, using a SUV cut-off of 1.26. For ¹⁸F-FDG, using a SUV cut-off of 2.77, the sensitivity and specificity were 83.3% and 71.4%, respectively. According to ROC analysis, the ROC curves for ¹¹C-Choline, ¹⁸F-FAMT, and ¹⁸F-FDG were 0.855, 0.734, and 0.847, respectively. ¹¹C-Choline PET is superior in the visualization of musculoskeletal tumors with high contrast imaging, whereas the combination of ¹⁸F-FAMT and ¹⁸F-FDG PET provides valuable information for the preoperative planning in patients with musculoskeletal tumors.
Journal of Biomedicine and Biotechnology 01/2011; 2011:807929. · 2.44 Impact Factor
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ABSTRACT: Optical imaging essentially refers to in vivo fluorescence imaging and bioluminescence imaging. These types of imaging are widely used visualization methods in biomedical research and are important in molecular imaging. A new generation of imaging agents called multimodal probes have emerged in the past few years. These probes can be detected by two or more imaging modalities, which harnesses the strengths of the different modalities and enables researchers to obtain more information than can be achieved using only one modality. Owing to its low cost and the large number of probes available, the optical method plays an important role in multimodality imaging. In this mini-review, we describe the available multimodal imaging probes for in vivo imaging that combine optical imaging with other modalities.
Contrast Media & Molecular Imaging 01/2011; 6(4):169-77. · 3.33 Impact Factor
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Journal of Biomedicine and Biotechnology 01/2011; 2011:673697. · 2.44 Impact Factor
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ABSTRACT: Cognitive neuroscience, which studies the biological basis of mental processes, widely uses neuroimaging technologies like functional magnetic resonance imaging and positron emission tomography (PET) to study the human brain. Small laboratory animals, like rodents, are commonly used in brain research and provide abundant models of human brain diseases. The development of high-resolution small-animal PET and various radiotracers together with sophisticated methods for analyzing functional brain imaging data have accelerated research on brain function and neurotransmitter release during behavioral tasks in rodents. In this review, we first summarize advances in the methodology of cognitive research brought about by the development of sophisticated methods for whole-brain imaging analysis and improvements in neuroimaging protocols. Then, we discuss basic mechanisms related to metabolic changes and the expression of neurotransmitters in various brain areas during task-induced neural activity. In particular, we discuss glucose metabolism imaging and brain receptor imaging for various receptor systems. Finally, we discuss the current status and future perspectives. Mechanisms of neurotransmitter expression will probably become an increasingly important field of study in the future, leading to more collaboration between investigators in fields such as computational and theoretical neuroscience.
Neuroscience Research 01/2011; 70(2):133-43. · 2.25 Impact Factor
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ABSTRACT: The purpose of this study was to assess the therapeutic effect of positron emission tomography agent [¹⁸F]-labeled 2-deoxy-2-fluoro-d-glucose (¹⁸F-FDG) in a colorectal cancer mouse model. Three (3) tumor-bearing mice groups were treated with different doses of ¹⁸F-FDG. Mice were imaged by positron emission tomography with ¹⁸F-FDG before and after treatment weekly and the tumor growth rate was calculated. Tumor, brain, heart, and kidney of mice were analyzed for expression of glucose transporters and vascular endothelial growth factor (VEGF) by immunofluorescent staining, and the presence of apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) method. All 3 treated groups showed significant ¹⁸F-FDG reduction compared with the control group (p < 0.05). With higher treatment dose, better treatment response was observed. The tumor growth rate of all 3 treated groups was also significantly decreased after treatment (p < 0.05). Immunohistochemistry showed that tumors expressed more glucose transporters than in brain, heart, and kidney. The ¹⁸F-FDG treatment of mice resulted in apoptotic cell death in all 3 treated groups, which showed significant higher apoptotic cells than the control group (p < 0.05). The study suggests that ¹⁸F-FDG has a therapeutic effect in colonic cancer animal model, which indicates the potential for the development of positron therapy for colonic cancer and other cancers.
Cancer Biotherapy & Radiopharmaceuticals 12/2010; 25(6):733-40. · 1.44 Impact Factor
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ABSTRACT: Embryonic stem cells (ESCs) have the most pluripotent potential of any stem cell. These cells, isolated from the inner cell mass of the blastocyst, are "pluripotent," meaning that they can give rise to all cell types within the developing embryo. As a result, ESCs have been regarded as a leading candidate source for novel regenerative medicine therapies and have been used to derive diverse cell populations, including myocardial and endothelial cells. However, before they can be safely applied clinically, it is important to understand the in vivo behavior of ESCs and their derivatives. In vivo analysis of ESC-derived cells remains critically important to define how these cells may function in novel regenerative medicine therapies. In this review, we describe several available imaging modalities for assessing cell engraftment and discuss their strengths and limitations. We also analyze the applications of these modalities in assessing the utility of ESCs in regenerative medicine therapies.
European Journal of Nuclear Medicine 11/2010; 38(4):774-84. · 4.53 Impact Factor
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ABSTRACT: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive method to excite neurons in the brain. However, the underlying mechanism of its therapeutic effects in stroke remains unclear. The aim of this study was to investigate the neuroprotective effect of high-frequency rTMS in a rat model of transient cerebral ischaemia using positron emission tomography (PET).
Sprague-Dawley rats (n=30) were anaesthetized with chloral hydrate and subjected to 90 min of intraluminal middle cerebral artery occlusion (MCAO) with subsequent reperfusion in three groups: control (n=10), rTMS (n=10), or sham-rTMS groups (n=10). In the rTMS group, rTMS was given 1 h after ischaemia and every 24 h for 7 days after MCAO. In all three groups, small-animal PET (microPET) imaging with (18)F-FDG was used to evaluate brain glucose metabolism. Apoptotic molecules were measured in the infarct margin using immunohistochemical staining.
The neurological scores of the rats in the rTMS group were higher than in those of the control group over the whole 7-day observation period. The total, cortical and striatal infarct volumes were significantly less in the rTMS group than in the control group, as measured by 2,3,5-triphenyltetrazolium chloride staining. (18)F-FDG microPET images showed significantly higher standardized uptake values in the cortex and striatum in the rTMS group than in the control group in the affected hemisphere. The number of cells positive for caspase-3 was significantly lower in the rTMS group than in the control group, while the Bcl-2/Bax ratio was significantly higher in the rTMS group than in the control group.
rTMS therapy increased glucose metabolism and inhibited apoptosis in the ischaemic hemisphere. (18)F-FDG PET could be used to monitor rTMS therapy in transient cerebral ischaemia in animal studies and in future clinical trials.
European Journal of Nuclear Medicine 05/2010; 37(5):954-61. · 4.53 Impact Factor
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ABSTRACT: Hypoxia, a condition of insufficient O2 to support metabolism, occurs when tumor outgrows its vascular supply. As the tumor cells gradually become hypoxic, they adapt by up-regulating the production of numerous proteins that promote their survival and metastatic spread. These changes result in patients with hypoxic tumors invariably experience poor outcome to treatment. Accordingly, the development of assays for the detection of hypoxia in patients in order to predict outcome and identify patients with a worse prognosis and/or patients that would benefit from appropriate treatments is of potential interest to researchers and clinicians. A variety of invasive and noninvasive approaches have been developed to detect tumor oxygenation. These approaches including oxygen-sensitive electrodes and hypoxia marker techniques using various labels that can be detected by different methods such as autoradiography, immunohistochemistry, nuclear medicine imaging and magnetic resonance imaging. In this review, we will discuss the non-invasive, potentially providing a quantitative and high resolution three-dimensional molecular imaging modality with positron emission tomography which is available to measure tumor hypoxia.
Current Medical Imaging Reviews 01/2010; 6(1):8-16. · 0.71 Impact Factor
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ABSTRACT: In recent years, the emerging and advances of non-invasive in vivo stem cell imaging has significantly contributed to the real-time tracking of transplanted stem cells as well as monitoring their proliferation, migration and persistence in live animals and ultimately possibly in humans. This review summarized the different in vivo imaging modalities for imaging stem cell, especially for its monitoring viability, death and proliferation; and discussed the strategies of combined multimodality approaches for monitoring of the fate of transplanted stem cell by offering the opportunity to distinguish different biological and biochemical processes.
01/2010; 2:171-177.
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ABSTRACT: Pancreatic carcinoma is a malignant tumor with poor prognosis and its early detection is still a clinical problem. The aim of this study was to evaluate the efficacy of carbon-11-labeled acetate (11C-acetate)-positron emission tomography (PET) for the detection of pancreatic carcinoma in a BxPC-3 human pancreatic carcinoma xenograft-bearing immunodeficiency BALB/c-nu nude mice model.
Whole-body 11C-acetate and fluorine-18-labeled fluorodeoxyglucose (F-FDG) micro-PET imaging were performed weekly on BxPC-3 human pancreatic carcinoma xenograft-bearing BALB/c-nu nude mice from the 2nd week after tumor cell inoculation. Regions of interest method and tumor-to-nontumor ratio (T/N ratio) were used for semiquantitative evaluation. Tumor proliferation was evaluated by immunohistochemistry analysis of proliferating cell nuclear antigen.
Radiotracer accumulation in the tumor xenografts could be detected 1 week earlier in 11C-acetate-PET than that in 18F-FDG-PET. Peak T/N ratio was obtained at the 5th week in 11C-acetate-PET and at the 4th week in 18F-FDG-PET. T/N ratio in 11C-acetate-PET was lower than that in 18F-FDG-PET during the same period. By visual evaluation, tumor xenografts were more easily observed in 11C-acetate-PET than in 18F-FDG-PET in most of the mice. Linear correlation analysis indicated T/N ratios in C-acetate-PET had no significant correlation with those in 18F-FDG-PET. Tumor size, T/N ratio in 11C-acetate-PET, and T/N ratio in 18F-FDG-PET were not found to be significantly correlated with tumor proliferating cell nuclear antigen expression.
11C-acetate-PET imaging can be used for the detection of pancreatic carcinoma. In the early stage of tumor growth, 11C-acetate-PET has better detectability than that of 18F-FDG-PET.
Nuclear Medicine Communications 09/2009; 30(12):971-7. · 1.40 Impact Factor
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ABSTRACT: The mechanism underlying the antiepileptic function of deep brain stimulation (DBS) of the anterior thalamic nucleus (ATN) remains unknown, presumably related to functional lesioning of target. We measured the regional normalized cerebral metabolic rate of glucose (nCMRglc) with (18)F-fluorodeoxyglucose (FDG)-MicroPET in animals receiving either ATN stimulation or lesioning. Bilateral ATN stimulation reversibly increased glucose uptake in the target region, the thalamus and hippocampus, and decreased glucose uptake in the cingulate cortex and frontal cortex. However, bilateral ATN lesioning decreased glucose uptake only in the target region. Animals with bilateral ATN lesions showed no metabolic changes after ATN stimulation. Thus, bilateral DBS of the ATN reversibly induces metabolic activation of the target area and modulates energy metabolism in remote brain regions via efferent or afferent fibers in non-epileptic rats. DBS of the ATN may work by a different mechanism than ATN lesioning.
Neurobiology of Disease 04/2009; 34(3):477-83. · 5.40 Impact Factor
