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1.
Purpose High blood glucose levels may decrease the sensitivity of 2-deoxy-2-[F-18]fluoro-d-glucose (FDG)-positron emission tomography (PET). The goal of this study was to assess whether intravenous (i.v.) insulin followed by FDG injection 60 minutes later could decrease the blood glucose level of hyperglycemic patients without altering muscular, liver, or lung FDG uptake.Methods We evaluated 53 diabetic patients with a fasting glycemia higher than 7.0 mmol/l. The control group consisted of 53 nondiabetic patients with a normal fasting glycemia. Sixty minutes before FDG injection, all diabetic patients received up to two intravenous bolus of insulin. Regions of interest were drawn over the lungs, heart, liver, skeletal muscles, and over the most active lung nodule, if present, to calculate a standardized uptake value (SUV) normalized to the lean body weight.Results After one or two boluses of insulin (mean 3.4 units), 39 diabetic patients decreased their blood glucose level from 9.4 ± 1.8 to 6.1 ± 1.3 mmol/l. In 14 patients, two doses of insulin (mean 4.5 ± 2.3 units) were not sufficient, but managed to decrease the blood glucose level from 10.6 ± 2.1 to 9.1 ± 2.1 mmol/l. There was no significant difference for the SUV calculated on the lung, liver, heart, and skeletal muscles. No differences were noted in lung tumor uptake in patients who received insulin compared to the control group.Conclusions With a sufficient waiting period between the insulin and FDG injections, an i.v. bolus of insulin makes it possible to effectively decrease glycemia of diabetic patients without increasing muscular FDG uptake.  相似文献   

2.

Purpose

The aim of the present study was to evaluate the use of 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG) as a noninvasive strategy to assess the time course of inflammatory processes after inhalation of ZnO nanoparticles (NPs) in rats.

Procedures

Healthy, male Sprague–Dawley rats (n?=?30) were divided in two groups of 15 animals each. Animals from one group (n?=?15) were submitted to ZnO NPs inhalation in a chamber (10 nm to 4 μm particle size; maximum in number concentration, ~200 nm; concentration?=?245 mg/m3). Animals from the other group (n?=?15, sham group) were also exposed following the same procedure, but no NPs were introduced into the chamber. Six animals per group were submitted to [18F]FDG-positron emission tomography (PET) studies at days 1, 7, and 28 after exposition, and the [18F]FDG influx constant (K i ) for the lungs was calculated using Patlak graphical analysis and an image derived blood input function. Nine animals per group were killed at 1, 7 and 28 days after exposure (n?=?3 per group and time point), and the lungs were harvested and submitted to immunohistochemical and histological analysis.

Results

Significantly higher mean whole-lung K i values were obtained for animals exposed to NPs at days 1 and 7 after exposure (0.0045?±?0.0016 min?1 and 0.0047?±?0.0015 min?1, respectively) compared to controls (0.0024?±?0.0010 min?1 and 0.0019?±?0.0011 min?1 at 1 and 7 days, respectively). The K i value for exposed animals dropped to 0.0023?±?0.0010 min?1 at day 28. This value was not significantly different from the values obtained at 1, 7, and 28 days for the control group. Immunofluorescence staining on lung tissue slices from animals exposed to ZnO NPs showed an increase in CD11b reactivity at days 1 and 7, followed by a decrease in CD11b positive cells at 28 days. Hematoxylin–eosin staining showed histological alterations in the exposed lungs to ZnO NPs at days 1 and 7 that recovered at 28 days postexposure.

Conclusions

The [18F]FDG influx rate constant (K i ) could be determined by PET using Patlak analysis and a corrected image derived input function. Higher K i values were obtained for animals exposed to ZnO NPs at days 1 and 7 after exposition. These results were in good concordance with immunohistochemical assays performed on harvested tissue samples.  相似文献   

3.
Purpose

An important issue in rodent imaging is the question whether a mixed population of male and female animals can be used rather than animals of a single sex. For this reason, the present study examined the test-retest stability of positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) in male rats and female rats at different phases of the estrous cycle.

Procedures

Long–Evans rats (age 1 year) were divided into three groups: (1) males (n?=?6), (2) females in metestrous (low estrogen levels, n?=?9), and (3) females in proestrous (high estrogen levels, n?=?7). Two standard [18F]FDG scans with rapid arterial blood sampling were made at an interval of 10 days in subjects anesthetized with isoflurane and oxygen. Body temperature, heart rate, and blood oxygenation were continuously monitored. Regional cerebral metabolic rates of glucose were calculated using a Patlak plot with plasma radioactivity as input function.

Results

Regional metabolic rate of glucose (rCMRglucose) in male and female rats, or [18F]FDG uptake in females at proestrous and metestrous, was not significantly different, but females showed significantly higher standardized uptake values (SUVs) and Patlak flux than males, particularly in the initial scan. The relative difference between the scans and the test-retest variability (TRV) were greater in females than in males. Intra-class correlation coefficients (ICCs) of rCMRglucose, SUV, normalized SUV, and glucose flux were good to excellent in males but poor to moderate in females.

Conclusions

Based on these data for [18F]FDG, the mixing of sexes in imaging studies of the rodent brain will result in an impaired test-retest stability of PET data and a need for larger group sizes to maintain statistical power in group comparisons. The observed differences between males and females do not indicate any specific gender difference in cerebral metabolism but are related to different levels of non-radioactive glucose in blood plasma during isoflurane anesthesia.

  相似文献   

4.
Before studying the impact of 2-deoxy-2-[F-18]fluoro-d-glucose (FDG) imaging with a dual-head coincidence gamma camera (DHC) for the follow-up of animal tumor models, we wanted to optimize this technique.Methods Three different animal tumor models (osteosarcoma, melanoma, and breast cancer) were studied after FDG injection. Dynamic and dual time point FDG/DHC imaging were studied from one hour to five hours postinjection. In vitro tumor cell FDG uptake was assessed in eight different tumor cell lines. In one model (osteosarcoma), tumor growth, lung metastasis emergence, and survival were assessed by classical clinical follow-up and compared to FDG imaging in a control group (n = 6) and in a group treated by endostatin liposome complexes (n = 6).Results Images obtained five hours after injection were more reliable for tumor growth follow-up than standard images (one hour). In vitro tumor cell FDG uptake confirmed in vivo imaging studies. In eight different tumor cell lines the FDG uptake was higher after five hours incubation than after one hour (p < 0.002). With FDG follow-up, we found that FDG uptake was strongly correlated with survival and that lung metastasis larger than 5 mm could be detected.Conclusion Using the optimization proposed above, DHC/FDG functional imaging seems to be a powerful tool to study rat tumor models and to help develop novel cancer therapies.  相似文献   

5.

Purpose

The phosphatidyl inositol 3 kinase, AKT and mammalian target of rapamycin are frequently deregulated in human cancer and are among one of the most promising targets for cancer therapy. AZD5363 (AstraZeneca) is an AKT inhibitor in phase 1 clinical trials. Given its utility in assessing glucose metabolism, we investigated the role of 2-Deoxy-2-[18F]fluoro-d-glucose (18F-FDG) positron emission tomography (PET) as a biomarker to demonstrate target inhibition and its potential to predict and demonstrate the anti-tumour activity of AZD5363.

Methods

18F-FDG PETscans were performed in nude mice in a number of xenograft models (U87-MG glioblastoma, BT474C breast carcinoma and Calu-6 lung). Mice were fasted prior to imaging, and either static or dynamic 18F-FDG PET imaging was performed.

Results

We have shown that 18F-FDG uptake in tumour xenografts was reduced by 39 % reduction compared to vehicle after a single dose of AZD5363, demonstrating activation of the AKT pathway after only 4 h of dosing. Multiple doses of AZD5363 showed an anti-tumour volume effect and a reduction in 18F-FDG uptake (28 % reduction compared to vehicle), highlighting the potential of 18F-FDG PET as an efficacy biomarker. Furthermore, the degree of inhibition of 18F-FDG uptake corresponded with the sensitivity of the tumour model to AZD5363. The use of dynamic 18F-FDG PET and a two-compartmental analysis identified the mechanism of this change to be due to a change in cellular uptake of 18F-FDG following administration of AZD5363.

Conclusions

We conclude that 18F-FDG PET is a promising pharmacodynamic biomarker of AKT pathway inhibition, with potential to predict and demonstrate anti-tumour activity. It is a biomarker that may stop ineffective drug schedules, helping to make early stop decisions and identify responding subsets of patients, resulting in improved clinical decision making both during drug development and patient management.  相似文献   

6.

Purpose

The purpose of this study is to evaluate the 18 kDa translocator protein (TSPO) radioligand [18F]N-fluoroacetyl-N-(2,5-dimethoxybenzyl)-2-phenoxyaniline ([18F]PBR06) as a positron emission tomography (PET) imaging biomarker of stroke-induced neuroinflammation in a rodent model.

Procedures

Stroke was induced by transient middle cerebral artery occlusion in Balb/c mice. Dynamic PET/CT imaging with displacement and preblocking using PK111195 was performed 3 days later. PET data were correlated with immunohistochemistry (IHC) for the activated microglial markers TSPO and CD68 and with autoradiography.

Results

[18F]PBR06 accumulation peaked within the first 5 min postinjection, then decreased gradually, remaining significantly higher in infarct compared to noninfarct regions. Displacement or preblocking with PK11195 eliminated the difference in [18F]PBR06 uptake between infarct and noninfarct regions. Autoradiography and IHC correlated well spatially with uptake on PET.

Conclusions

[18F]PBR06 PET specifically images TSPO in microglial neuroinflammation in a mouse model of stroke and shows promise for imaging and monitoring microglial activation/neuroinflammation in other disease models.  相似文献   

7.
Objectives To investigate the existence of quantum metabolic values in various subtypes of non-Hodgkin’s lymphoma (NHL). Methods Fifty-eight patients with newly diagnosed NHL and positron emission tomography (PET) performed within three months of biopsy were included. The standardized uptake value (SUV) from PET over the area of biopsy and serum glucose [Glc] were recorded. The group glucose sensitivity(G) for indolent and aggressive NHL was obtained by linear regression with ln(SUV) = G·ln[Glc] + C, where C is a constant for the group. Finally, the individual’s glucose sensitivity (g) was obtained by g = {ln(SUV)-C}/ln[Glc], along with their means in various subtypes of NHL. To further investigate the influence of extreme [Glc] conditions, the SUVs corrected by the individually calculated g at various glucose levels, [Glc′] using SUV′ =SUV·{[Glc′]/[Glc]} g , were compared to the original SUVs for both indolent and aggressive NHL. Results The averaged g (=G) for aggressive was significant different from that for indolent NHL (−0.94 ± 0.51 vs. +0.13 ± 0.10, respectively, p < 0.00005). There were significant differences in SUV for [Glc] < 80 or >110 mg/dl for both types of NHL. Unlike overlap among SUVs between NHL subtypes, the g value clearly categorized them into two distinct groups with positive (near-zero) and negative g values (around −1) for the indolent and aggressive NHLs, respectively. Conclusions Distinct quantum metabolic values of −1 and 0 were noted in NHL. Aggressive NHL has a more negative value (or higher glucose sensitivity) than that of indolent and, thus, is more susceptible to extreme glucose variation.  相似文献   

8.
Brown fat uptake of 2-deoxy-2-[F-18]fluoro-d-glucose (FDG) on a positron emission tomography (PET) scan limits the ability to assess for cancer. Drugs such as benzodiazepine, propranolol, and reserpine have been proposed to reduce this uptake, but the studies have been either small clinical or preclinical trials. As an alternative, we evaluated the effect of controlling the patient’s environmental temperature on brown fat uptake of FDG. Method From January 1, 2002 to November 30, 2004, patients were identified who had (1) a pattern of FDG uptake in the neck/paravertebral areas suggestive of brown fat, (2) a repeat FDG-PET scan after control of the patient’s environmental temperature, and (3) no evidence of cancer in the neck/paravertebral areas by other diagnostic methods. For the follow-up PET scan, all patients wore warm clothing and avoided exposure to cold air during their transit to our facility. After arrival, patients were kept in a separate temperature-controlled room (at least 75°F) for 15 minutes to two hours before FDG injection as well as during the uptake phase. Four physicians blindly and retrospectively assessed the FDG uptake in the neck and paravertebral regions on all initial and temperature-controlled PET scans by visually grading the radioactivity on a semiquantitative scale (0 = background, 1+ = background but <liver, 2+ = equal to liver, 3+ >liver). The changes in maximal SUVs were determined in the left and right neck region. Data were evaluated using a two-tail t-test. Results Ten patients met the above criteria. The median age was 32 years with a range of 11–58 years. In comparing the semiquantitative uptake and the SUVs of FDG in the neck and paravertebral areas on the initial PET scan to the temperature-controlled PET scan, the mean decrease and the standard deviation of the decrease demonstrated a statistically significant decrease in with P values range from <0.02 to <0.001. Conclusion Controlling the patient’s environmental temperature prior to the dosing and during the uptake phase can significantly reduce FDG uptake in brown fat in the neck and paravertebral areas. Further studies are warranted to determine the most effective protocol to control the patient’s environmental temperature in order to minimize brown fat uptake.  相似文献   

9.
Purpose The aim of this study was to validate quantitative metabolic response of tumors to a treatment measured by longitudinal 2-deoxy-2-[18F]fluoro-d-glucose (FDG) micro positron emission tomography (microPET) as a robust tool for preclinical evaluation of new anticancer agents.Procedures Severe combined immunodeficiency mice with CWR22 xenografts were intravenously treated with bortezomib (Velcade) at 0.8 mg/kg on days 0, 3, 7, 10, and 14 and imaged with FDG microPET before, during and after treatment. Quantitative indices of tumor FDG uptake were developed.Results FDG microPET images successfully revealed the gradual reduction of tumor FDG uptake on day 4 onward despite no absolute tumor shrinkage. The standardized uptake values of FDG in tumors was reduced to 43% of the baseline values. Using the total tumor FDG uptake as the viable tumor burden, we found 86% tumor inhibition, compared to a 55% tumor growth inhibition in tumor volume measurement.Conclusion FDG microPET imaging can provide an additional dimension of the efficacy of anticancer therapies that may otherwise be underestimated by tumor volume measurement.  相似文献   

10.
Molecular Imaging and Biology - Ischemic stroke is a leading cause of disability worldwide. The volume of necrotic core in affected tissue plays a major role in selecting stroke patients for...  相似文献   

11.
Akintayo  Akinyemi A.  Abiodun-Ojo  O. A.  Weber  C.  Sharma  J.  Cohen  C.  Sica  G.  Halkar  R.  Goodman  M. M.  Schuster  D. M. 《Molecular imaging and biology》2019,21(5):818-824
Molecular Imaging and Biology - To evaluate the ability of anti-1-amino-3-anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid ([18F]fluciclovine) positron emission tomography/X-ray computed...  相似文献   

12.
13.
Purpose  This study was designed to assess changes in brain glucose metabolism in rats after visual stimulation. Materials and methods  We sought to determine whether visual activation in the rat brain could be detected using a small-animal positron emission tomography (PET) scanner and 2-deoxy-2-[18F]fluoro-d-glucose (FDG). Eleven rats were divided into two groups: (a) five animals exposed to ambient light and (b) six animals stimulated by stroboscopic light (10 Hz) with one eye covered. Rats were injected with FDG and, after 45 min of visual stimulation, were sacrificed and scanned for 90 min in a dedicated PET tomograph. Images were reconstructed by a three-dimensional ordered subset expectation maximization algorithm (1.8 mm full width at half maximum). A region-of-interest (ROI) analysis was performed on 14 brain structures drawn on coronal sections. Statistical parametric mapping (SPM) adapted for small animals was also carried out. Additionally, the brains of three rats were sliced into 20-μm sections for autoradiography. Results  Analysis of ROI data revealed significant differences between groups in the right superior colliculus, right thalamus, and brainstem (p ≤ 0.05). SPM detected the same areas as the ROI approach. Autoradiographs confirmed the existence of hyperactivation in the left superior colliculus and auditory cortex. Conclusions  To our knowledge, this is the first report that uses FDG-PET and SPM analysis to show changes in rat brain glucose metabolism after a visual stimulus.  相似文献   

14.
Incidental adrenal lesions found on anatomic imaging are not uncommon. 2-Deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET) imaging is highly accurate in the differentiation of benign from malignant adrenal lesions, both in patients with proven malignancy and with adrenal lesions detected incidentally. A 60-year-old white female with a history of lower mid-back pain underwent computerized tomography (CT) imaging that identified a 15-cm complex mass within the left adrenal gland with soft tissue, cystic, and adipose components. FDG-PET imaging showed significant hypermetabolic activity within portions of the mass with central photopenia suggesting a malignant lesion with central necrosis. Surgical excision and pathological examination, however, revealed a benign adrenal myelolipoma with extensive adenomatous and hematopoietic elements. Prior reports of adrenal myelolipoma evaluated with FDG-PET imaging have described no significant FDG uptake within these benign tumors. This case is an unusual example of histologically proven benign adrenal myelolipoma that was hypermetabolic on FDG-PET imaging. Correlation of pathologic and imaging findings demonstrated that the hypodense regions on CT were hypometabolic on FDG-PET and corresponded to cystic necrosis and adipose elements, whereas the adenomatous and hematopoietic elements were hypermetabolic.  相似文献   

15.
Systemic lupus erythematosus (SLE) and lymphoma are disease entities that often have similar presenting signs and symptoms that can complicate or delay definitive diagnosis. 2-Deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography (FDG-PET) has become a valuable tool in the diagnosis, staging, and evaluation of response to therapy in lymphoma patients. However, its utility in patients with SLE has been limited to the central nervous system. Significant FDG uptake has not been previously reported in lymphadenopathy associated with SLE. The case presented is an example of histologically proven benign adenopathy in a 16-year-old female with SLE that was hypermetabolic on FDG-PET imaging. It highlights the importance of recognizing that widespread inflammatory adenopathy in SLE can mimic the pattern of FDG uptake seen with lymphoma at PET imaging.  相似文献   

16.
Molecular Imaging and Biology - The purpose of this study is to prospectively evaluate the performance of sodium 18F]fluoride (Na[18F]F)/2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) simultaneous...  相似文献   

17.
PET and [18F]fluoro-L-m-tyrosine (FMT) have been used to quantify presynaptic striatal dopamine (DA) function in Parkinson disease (PD) and in primate models of PD. While dynamic imaging and a metabolite-corrected blood input function can be used to determine striatal FMT uptake rate constants (Ki), a simpler analytic approach using shorter imaging times is desirable for clinical studies. We compared the utility of using striatal Ki values versus striatal count ratios in two groups of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. Striatal DA content was also measured in one of the groups to evaluate the relationship between the PET measures and an independent measure of striatal dopamine. Striatal Ki values were significantly correlated with striatal count ratios using the cerebellum as the denominator. Both Ki values and ratios were also correlated with striatal DA content. In addition, putamen-cerebellum ratios and putamen Ki values showed similar separation between baseline and post-MPTP values. These findings suggest that a simple ratio approach to analyzing FMT PET data may be a useful alternative to a kinetic approach especially for clinical applications.  相似文献   

18.
[(18)F]fluoroethoxybenzovesamicol ([(18)F]FEOBV) is one of the most promising radioligands for imaging the vesicular ACh transporter (VAChT) with positron emission tomography (PET). We report here that this method can detect subtle cholinergic terminals losses such as those associated with aging, or those following a partial lesion of the nucleus basalis magnocellularis (NBM). Twenty-one adult rats were evenly distributed in three groups including 1) aged rats (18 months); 2) young rats (3 months); and 3) rats with unilateral lesion of the NBM, following a local stereotaxic infusion of 192 IgG-saporin. In both normal and lesioned rats, our results revealed the highest [(18)F]FEOBV binding to be in the striatum, followed by similar values in both frontal cortex and thalamus, while lower values were observed in both hippocampus and temporo-parietal cortex. This binding distribution is consistent with the known anatomy of brain cholinergic systems. In the lesioned rats, [(18)F]FEOBV binding was found to be reduced mostly in the ventral frontal cortex on the side of the lesion, but some reductions were also observed in the homologous region of the contralateral hemisphere. Aging was found to be associated with a [(18)F]FEOBV binding reduction limited to the hippocampus of both hemispheres. [(18)F]FEOBV appears to be a very promising marker for the in vivo quantification of the brain VAChT; PET imaging of this agent allows in vivo detection of both physiological and pathological reductions of cholinergic terminals density.  相似文献   

19.

Purpose

We aimed to elucidate trans-1-amino-3-[18F]fluorocyclobutanecarboxylic acid (anti-[18F]FACBC) uptake mechanisms in inflammatory and tumor cells, in comparison with those of l-[methyl-11C]methionine ([11C]Met) and 2-deoxy-2-[18F]fluoro-d-glucose ([18F]FDG).

Procedures

Using carbon-14-labeled tracers, in vitro time-course, pH dependence, and competitive inhibition uptake experiments were performed in rat inflammatory (T cells, B cells, granulocytes, macrophages), prostate cancer (MLLB2), and glioma (C6) cells.

Results

Anti-[14C]FACBC uptake ratios of T/B cells to tumor cells were comparable, while those of granulocytes/macrophages to tumor cells were lower than those for [14C]FDG. Over half of anti-[14C]FACBC uptake by T/B and tumor cells was mediated by Na+-dependent amino acid transporters (system ASC), whereas most [14C]Met transport in all cells was mediated by Na+-independent carriers (system L).

Conclusions

The low anti-[18F]FACBC accumulation in granulocytes/macrophages may be advantageous in discriminating inflamed regions from tumors. The significant anti-[18F]FACBC uptake in T/B cells may cause false-positives in some cancer patients who undergo FACBC-positron emission tomography (PET).  相似文献   

20.
Molecular Imaging and Biology - Although a preparation method for F-18-labeled proteins that used a cell-free translation system and 4-[18F]fluoro-L-proline instead of L-proline has been reported,...  相似文献   

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