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1.

Purpose

Hypoxia is an important factor influencing tumor progression and treatment efficacy. The aim of this study was to investigate the repeatability of hypoxia PET imaging with [18F]HX4 in patients with head and neck and lung cancer.

Methods

Nine patients with lung cancer and ten with head and neck cancer were included in the analysis (NCT01075399). Two sequential pretreatment [18F]HX4 PET/CT scans were acquired within 1 week. The maximal and mean standardized uptake values (SUVmax and SUVmean) were defined and the tumor-to-background ratios (TBR) were calculated. In addition, hypoxic volumes were determined as the volume of the tumor with a TBR >1.2 (HV1.2). Bland Altman analysis of the uptake parameters was performed and coefficients of repeatability were calculated. To evaluate the spatial repeatability of the uptake, the PET/CT images were registered and a voxel-wise comparison of the uptake was performed, providing a correlation coefficient.

Results

All parameters of [18F]HX4 uptake were significantly correlated between scans: SUVmax (r?=?0.958, p?<?0.001), SUVmean (r?=?0.946, p?<?0.001), TBRmax (r?=?0.962, p?<?0.001) and HV1.2 (r?=?0.995, p?<?0.001). The relative coefficients of repeatability were 15 % (SUVmean), 17 % (SUVmax) and 17 % (TBRmax). Voxel-wise analysis of the spatial uptake pattern within the tumors provided an average correlation of 0.65?±?0.14.

Conclusion

Repeated hypoxia PET scans with [18F]HX4 provide reproducible and spatially stable results in patients with head and neck cancer and patients with lung cancer. [18F]HX4 PET imaging can be used to assess the hypoxic status of tumors and has the potential to aid hypoxia-targeted treatments.
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2.

Objective

We evaluated the uptake of 2-deoxy-2-18F-fluoro-d-glucose (FDG) and l-[methyl-11C]-methionine (MET) in patients with newly diagnosed intracranial meningiomas and correlated the results with tumor proliferation.

Methods

Data from 22 patients with newly diagnosed intracranial meningioma (12 grade I and 10 grade II) who underwent both FDG and MET brain PET/CT studies were retrospectively analyzed. The PET images were evaluated by a qualitative method and semiquantitative analysis using standardized uptake value (SUV) (SUVmax and SUVpeak) and tumor-to-reference tissue ratio (Tmax/N ratio and Tpeak/N ratio). Proliferative activity as indicated by the Ki-67 index was estimated in tissue specimens.

Results

MET PET/CT showed a higher detection rate of meningioma than did FDG PET/CT (100 vs. 46%, respectively). The Tmax/N ratio and Tpeak/N ratio on MET PET/CT were significantly higher than those on FDG PET/CT (p?<?0.001 and p?<?0.001, respectively). There was a significant difference between grades I and II with respect to FDG SUVmax (p?=?0.003), FDG SUVpeak (p?=?0.003), FDG Tmax/N ratio (p?=?0.02), FDG Tpeak/N ratio (p?=?0.006), MET SUVmax (p?=?0.002), MET SUVpeak (p?=?0.002), MET Tmax/N ratio (p?=?0.002), and MET Tpeak/N ratio (p?=?0.002). There was a significant correlation between Ki-67 index and FDG PET/CT for SUVmax (p?=?0.02), SUVpeak (p?=?0.005), and Tpeak/N ratio (p?=?0.05) and between Ki-67 index and MET PET/CT for SUVmax (p?=?0.004), SUVpeak (p?=?0.007), Tmax/N ratio (p?=?0.002), and Tpeak/N ratio (p?=?0.004).

Conclusion

MET PET/CT showed a high sensitivity compared with FDG PET/CT for detection of newly diagnosed WHO grades I and II intracranial meningiomas. Both FDG and MET uptake were found to be useful for evaluating tumor proliferation in meningiomas.
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3.

Purpose

The aim of this study was to determine the usefulness of MRI-assisted positron emission tomography (PET) parameters provided by simultaneous 18F-fluorocholine (FCH) PET/MRI for characterization of primary prostate cancer.

Methods

Thirty patients with localized prostate cancer (mean age 69.4?±?6.7 years) confirmed by biopsy were prospectively enrolled for simultaneous PET/MRI imaging. The patients underwent 18F-FCH PET/MRI 1 week before undergoing total prostatectomy. Multiple parameters of diffusion-weighted MRI [minimum and mean apparent diffusion coefficient (ADCmin and ADCmean)], metabolic PET [maximum and mean standardized uptake value (SUVmax and SUVmean)], and metabolic volumetric PET [metabolic tumor volume (MTV) and uptake volume product (UVP)] were compared with laboratory, pathologic, and immunohistochemical (IHC) features of the prostate cancer specimen. PET parameters were divided into two categories as follows: volume of interest (VOI) of prostate by SUV cutoff 2.5 (SUVmax, SUVmean, MTVSUV, and UVPSUV) and MRI-assisted VOI of prostate cancer (SUVmaxMRI, SUVmeanMRI, MTVMRI, and UVPMRI).

Results

The rates of prostate cancer-positive cases identified by MRI alone, 18F-FCH PET alone, and 18F-FCH PET/MRI were 83.3, 80.0, and 93.3 %, respectively. Among the multiple PET/MRI parameters, MTVMRI showed fair correlation with serum prostate-specific antigen (PSA; r?=?0.442, p?=?0.014) and highest correlation with tumor volume (r?=?0.953, p?<?0.001). UVPMRI showed highest correlation with serum PSA (r?=?0.531, p?=?0.003), good correlation with tumor volume (r?=?0.908, p?<?0.001), and it was significantly associated with Gleason score (p?=?0.041). High MTVMRI and UVPMRI values were significant for perineural invasion, lymphatic invasion, extracapsular extension, seminal vesicle invasion, and positive B-cell lymphoma 2 (Bcl-2) expression (all p?<?0.05).

Conclusion

Simultaneous 18F-FCH PET/MRI demonstrated a better diagnostic value for localized prostate cancer detection than each individual modality. MRI-assisted metabolic volumetric PET parameters (MTVMRI and UVPMRI) provided more accurate characterization of prostate cancer than conventional PET and MRI parameters.
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4.

Purpose

Malignant de novo lipogenesis is strongly linked to the aggressiveness of prostate cancer (PCa) under experimental conditions. 11C-Acetate PET/CT is a potential noninvasive biomarker of malignant lipogenesis in PCa, but its prognostic value is not known. The objective of this study was to analyse 11C-acetate PET/CT image metrics in relation to survival.

Methods

All patients undergoing 11C-acetate PET/CT in one university hospital from 2005 to 2011 due to PSA relapse after previous prostatectomy were retrospectively evaluated. Two groups of patients were compared: those who died from PCa and those who were censored. All previously reported findings of local recurrence, regional or distal lymph node metastases and bone metastases were counted and evaluated regarding 11C-acetate uptake intensity (SUVmax) and tumour volume. Total tumour volume and total lipogenic activity (TLA, summed SUVmax × TV) were calculated. Survival analysis in the entire study population was followed by Cox proportional hazards ratio (HR) analysis.

Results

A total of 121 patients were included, and 22 PCa-specific deaths were recorded. The mean PSA level at the time of PET was 2.69?±?4.35 ng/mL. The median follow-up of the study population was 79?±?28 months. PET identified at least one PCa lesion in 53 % of patients. Five-year PCa-specific survival after PET was 80 % and 100 % in patients with a positive and a negative PET scan, respectively (p?<?0.001). Time-to-death was linearly correlated with highest SUVmax (r?=??0.55, p?=?0.01) and nonlinearly with TLA (r?=??0.75, p?<?0.001). Multivariate analysis showed statistical significance for number of bone metastases (HR 1.74, p?=?0.01), tertile of TLA (HR 5.63, p?=?0.029) and postoperative Gleason score (HR 1.84, p?=?0.045).

Conclusion

Malignant 11C-acetate accumulation measured with PET/CT is a strong predictor of survival in the setting of PSA relapse after prostatectomy. The study provides further evidence for a quantitative relationship between malignant de novo lipogenesis and early death. 11C-Acetate PET/CT might be useful for identifying a high-risk population of relapsing patients in which therapies targeting malignant lipogenesis might be of particular benefit.
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5.

Purpose

68Ga-labeled prostate-specific membrane antigen (PSMA) ligand positron emission tomography/computed tomography (PET/CT) has shown promising results in patients with biochemical recurrence after primary therapy for prostate cancer. In this study, we evaluated the usefulness of PSMA I&T (imaging and therapy) PET/CT prior to radical prostatectomy.

Methods

The study population consisted of 21 patients with prostate cancer who underwent 68Ga-PSMA I&T PET/CT before either open or laparoscopic radical prostatectomy. Intraprostatic tumor extent, extracapsular extension (ECE) and seminal vesicle invasion (SVI) were assessed on the PET/CT scans. Tracer uptake was quantified in terms of standardized uptake values (SUVs). Imaging findings were correlated with final whole-gland histopathology.

Results

Of the 21 patients, two had T stage 2b disease, nine stage 2c, six stage 3a and four stage 3b. The median Gleason score was 7. The SUVmean of the primary tumors was 9.5?±?8.8. SUVmean was higher in tumors with ECE than in organ-confined tumors (13.8?±?11.0 vs. 5.6?±?3.2, p?=?0.029). Peak tracer uptake was significantly positively correlated with Gleason score (r s?=?0.49, p?=?0.025). Sensitivity, specificity, positive predictive value and negative predictive value were, respectively, 94.7%, 75.0%, 97.3% and 60.0% for tumor infiltration of an individual prostate lobe, 75.0%, 100.0%, 100.0% and 97.4% for SVI, and 90.0%, 90.9%, 90.0% and 90.9% for ECE, using an angulated contour of the prostate as the criterion. Tumor volume derived from 68Ga-PSMA I&T PET/CT was significantly correlated with preoperative prostate-specific antigen value (r p?=?0.75, p?<?0.001) and tumor volume on histopathology (r p?=?0.45, p?=?0.039).

Conclusions

68Ga-PSMA I&T PET/CT prior to radical prostatectomy can contribute to presurgical local staging of prostate cancer. In this pilot study, 68Ga-PSMA I&T PET/CT showed promising results for prediction of lobe infiltration, ECE and SVI.
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6.

Purpose

Complete fracture healing is crucial for good patient outcomes. A major complication in the treatment of fractures is non-union. The pathogenesis of non-unions is not always clear, although implant-associated infections play a significant role, especially after surgical treatment of open fractures. We aimed to evaluate the value of [18F]FDG PET in suspected infections of non-union fractures.

Methods

We retrospectively evaluated 35 consecutive patients seen between 2000 and 2015 with suspected infection of non-union fractures, treated at a level I trauma center. The patients underwent either [18F]FDG PET/CT (N?=?24), [18F]FDG PET (N?=?11) plus additional CT (N?=?8), or conventional X-ray (N?=?3). Imaging findings were correlated with final diagnosis based on intraoperative culture or follow-up.

Results

In 13 of 35 patients (37 %), infection was proven by either positive intraoperative tissue culture (N?=?12) or positive follow-up (N?=?1). [18F]FDG PET revealed 11 true-positive, 19 true-negative, three false-positive, and two false-negative results, indicating sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 85 %, 86 %, 79 %, 90 %, and 86 %, respectively. The SUVmax was 6.4?±?2.7 in the clinically infected group and 3.0?±?1.7 in the clinically non-infected group (p <0.01). The SUVratio was 5.3?±?3.3 in the clinically infected group and 2.6?±?1.5 in the clinically non-infected group (p <0.01).

Conclusion

[18F]FDG PET differentiates infected from non-infected non-unions with high accuracy in patients with suspected infections of non-union fractures, for whom other clinical findings were inconclusive for a local infection. [18F]FDG PET should be considered for therapeutic management of non-unions.
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7.

Purpose

PET with 18F-FDG has the potential to assess vascular macrophage metabolism. 18F-FDG is most often used in combination with contrast-enhanced CT to localize increased metabolism to specific arterial lesions. Novel 18F-FDG PET/MRI hybrid imaging shows high potential for the combined evaluation of atherosclerotic plaques, due to the superior morphological conspicuity of plaque lesions. The purpose of this study was to evaluate the reliability and accuracy of 18F-FDG PET/MRI uptake quantification compared to PET/CT as a reference standard in patients with carotid atherosclerotic plaques.

Methods

The study group comprised 34 consecutive oncological patients with carotid plaques who underwent both PET/CT and PET/MRI with 18F-FDG on the same day. The presence of atherosclerotic plaques was confirmed by 3 T MRI scans. Maximum standardized uptake values (SUVmax) for carotid plaque lesions and the average SUV of the blood pool within the adjacent internal jugular vein were determined and target-to-blood ratios (TBRs, plaque to blood pool) were calculated.

Results

Atherosclerotic lesions with maximum colocalized focal FDG uptake were assessed in each patient. SUVmax values of carotid plaque lesions were significantly lower on PET/MRI than on PET/CT (2.3?±?0.6 vs. 3.1?±?0.6; P?<?0.01), but were significantly correlated between PET/CT and PET/MRI (Spearman’s r?=?0.67, P?<?0.01). In contrast, TBRmax values of plaque lesions were similar on PET/MRI and on PET/CT (2.2?±?0.3 vs. 2.2?±?0.3; P?=?0.4), and again were significantly correlated between PET/MRI and PET/CT (Spearman’s r?=?0.73, P?<?0.01). Considering the increasing trend in SUVmax and TBRmax values from early to delayed imaging time-points on PET/CT and PET/MRI, respectively, with continuous clearance of radioactivity from the blood, a slight underestimation of TBRmax values may also be expected with PET/MRI compared with PET/CT.

Conclusion

SUVmax and TBRmax values are widely accepted reference parameters for estimation of the radioactivity of atherosclerotic plaques on PET/CT. However, due to a systematic underestimation of SUVmax and TBRmax with PET/MRI, the optimal cut-off values indicating the presence of inflamed plaque tissue need to be newly defined for PET/MRI.
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8.

Purpose

As there were few previous studies with a small number of subjects, the purpose of this was to evaluate the prognostic significance of 18F-FDG PET/CT in patients with distal bile duct cancer undergoing curative surgery.

Methods

The study included 40 patients (M/F?=?24:16; age 68.0?±?8.0 years) who underwent preoperative 18F-FDG PET/CT followed by curative surgical resection. The participant’s age, sex, Eastern Cooperative Oncology Group performance-status score, baseline serum CA 19-9 level, stage, pathologic T and N stages, tumor size, tumor grade, tumor growth pattern, R0 resection, and adjuvant therapy were included as clinicopathological variables for predicting overall survival. The PET variables were maximum standardized uptake value (SUVmax), average SUV (SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the tumor. The Kaplan-Meyer method and Cox proportional hazards model were used for the survival analysis.

Results

A total of 15 of 40 patients (37.5%) died during the follow-up period. In univariate analysis, low SUVmax (≤?2.7, p?=?0.0005) and low SUVavg (≤?2.6, p?=?0.0034) were significant predictors of poor overall survival. In multivariate analyses, only low SUVmax (HR?=?6.7016, 95% CI 1.9961–22.4993, p?=?0.0047) was an independent prognostic factor associated with poor overall survival.

Conclusion

The SUVmax of the primary tumor measured by 18F-FDG PET/CT was an independent significant prognostic factor for overall survival in patients with distal bile duct cancer. However, different results from a previous study warrant further large sample-sized study.
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9.

Objectives

Hepatic steatosis is common but less is known of the heterogeneity of hepatic fat distribution and its clinical significance. Our objective was to measure the regional variabilities within the liver of standardised uptake values (SUV) as potential markers of hepatic fat distribution heterogeneity.

Methods

Twenty-four patients having routine, clinically indicated PET/CT with 18F-FDG and a wide range of fatty liver severity were selected. Maximum SUV (SUVmax), average SUV (SUVave), both calculated using lean body mass, and CT density were measured in 12 × 2-cm diameter ROIs in each patient. SUVave was also measured over the left ventricular cavity (SUVLV). Mean values of SUV indices, their ratios with SUVLV, and CT density in the 12 ROIs were calculated. Regional variabilities of SUV indices were expressed as coefficients of variation (CV; standard deviation/mean). Body mass index (BMI) was estimated from height and body weight, and %body fat and lean body mass from height, weight and gender.

Results

Mean SUVmax/SUVave correlated significantly with mean CT density (r = ?0.51; p < 0.02). In contrast, mean SUVmax, mean SUVave and their ratios with SUVLV showed no correlation with CT density. Mean CT density correlated with weight (r = ?0.59; p < 0.005), BMI (r = ?0.57; p < 0.01) and %body fat (r = ?0.49; p < 0.02). Corresponding correlation coefficients for mean SUVmax/SUVave were 0.74 (p < 0.001), 0.65 (p < 0.001) and 0.46 (p < 0.03). In contrast, mean SUVmax, mean SUVave and their ratios with SUVLV showed no correlation with BMI, weight and %body fat. The CV of SUVmax/SUVave (r = ?0.67; p < 0.001), but not the CVs of SUVmax or SUVave, correlated with mean CT density.

Conclusions

SUVmax/SUVave and CT density are markers of hepatic steatosis. The regional variability of SUVmax/SUVave may be a marker of hepatic fat distribution heterogeneity. The novel concept is introduced that hepatic fat distribution heterogeneity may be a marker of hepatic pathology and of clinical value, and deserves further exploration with texture analysis.
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10.

Purpose

68Ga-labeled 1,4,7,10-tetraazacyclododecane-N,N′,N″,N?-tetraacetic acid-d-Phe1-Tyr3-octreotide (68Ga-DOTATOC) is taken up by activated macrophages, which accumulate in active inflammatory lesions. The purpose of this study was to investigate the feasibility of 68Ga-DOTATOC PET/CT for assessment of vulnerable plaque, by evaluating correlation between aortic uptake of 68Ga-DOTATOC and cardiovascular risk factors.

Methods

Fifty patients with neuroendocrine tumors who underwent 68Ga-DOTATOC PET/CT were retrospectively enrolled. The uptakes in the thoracic aorta were measured by two methods: multi-sample region-of-interest (ROI) method and single volume-of-interest (VOI) method. TBRmax-avg, TBRmean-avg, TBRmax-VOI, and TBRmean-VOI were defined by maximum and mean target-to-background ratio (TBR) from the multi-sample ROI method and the single VOI method, respectively.

Results

Framingham risk score (FRS) exhibited significant correlations with TBRmax-avg and TBRmean-avg, as well as TBRmax-VOI (r?=?0.3389–0.4593, P?<?0.05 for all). TBRmax-avg and TBRmax-VOI were significantly higher in high FRS group than in low FRS group (1.48?±?0.21 vs. 1.70?±?0.17, P?<?0.001 for TBRmax-avg and 1.90?±?0.33 vs. 2.25?±?0.36, P?=?0.002 for TBRmax-VOI). TBR exhibited high correlations between the two measuring methods (r?=?0.9684, P?<?0.001 for TBRmean-avg and TBRmean-VOI and r?=?0.8681, P?<?0.001 for TBRmax-avg and TBRmax-VOI).

Conclusions

68Ga-DOTATOC uptake in the thoracic aorta exhibited a significant correlation with cardiovascular risk factors, which suggests the feasibility of 68Ga-DOTATOC PET for vulnerable plaque imaging, with a simple measurement of the single VOI method that is comparable to the multi-sample ROI-based approach.
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11.

Purpose

There is currently no single modality for accurate characterization of enlarged mediastinal lymph nodes into benign or malignant. Recently 18F-fluorothymidine (FLT) has been used as a proliferation marker. In this prospective study, we examined the role of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) and 18F-FLT PET/CT in categorizing mediastinal lymph nodes as benign or malignant.

Materials and methods

A total of 70 consecutive patients with mediastinal lymphadenopathy detected on computed tomography (CT) or chest radiograph underwent whole body 18F-FLT PET/CT and 18F-FDG PET/CT (within 1 week of each other). Lymph nodal tracer uptake was determined by calculation of standardized uptake value (SUV) with both the tracers. Results of PET/CT were compared with histopathology of the lymph nodes.

Results

Histopathology results showed thirty-seven patients with sarcoidosis, seven patients with tuberculosis, nine patients with non-small cell lung cancer, five patients with Hodgkin’s lymphoma and twelve patients with non-Hodgkin’s lymphoma. The mean FDG SUVmax of sarcoidosis, tuberculosis, Hodgkin’s and non-Hodgkin’s lymphoma was 12.7, 13.4, 8.2, and 8.8, respectively, and the mean FLT SUVmax was 6.0, 5.4, 4.4, and 3.8, respectively. It was not possible to characterize mediastinal lymphadenopathy as benign or malignant solely based on FDG SUVmax values (p > 0.05) or FLT SUVmax values (p > 0.05). There was no significant difference in FDG uptake (p > 0.9) or FLT uptake (p > 0.9) between sarcoidosis and tuberculosis. In lung cancer patients, the FDG SUVmax and FLT SUVmax of those lymph nodes with tumor infiltration on biopsy was 6.7 and 3.9, respectively, and those without nodal infiltration was 6.4 and 3.7, respectively, and both the tracers were not able to characterize the nodal status as malignant or benign (p > 0.05).

Conclusion

Though 18F-FLT PET/CT and 18F-FDG PET/CT reflect different aspects of biology, i.e., proliferation and metabolism, respectively, neither tracer could provide satisfactory categorization of benign and malignant lymph nodes. The results of this study clearly suggest that differentiation of mediastinal nodes into benign and malignant solely based on SUVmax values cannot be relied upon, especially in settings where tuberculosis and sarcoidosis are common.
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12.

Purpose

Despite improved treatment options, multiple myeloma (MM) remains an incurable disease. The aim of this study was to investigate the prognostic value of positron emission tomography/computed tomography (PET/CT) using 18F-2’-deoxy-2’-fluorodeoxyglucose ([18F]FDG) in MM patients shortly before and ~100 days after allogeneic hematopoietic cell transplantation (allo-HCT).

Methods

In this retrospective analysis, we evaluated [18F]FDG-PET/CT-scans of 45 heavily pre-treated MM patients before and 27 patients after scheduled allo-HCT. All scans were qualitatively and semi-quantitatively assessed for the presence of active disease. Serological response was recorded according to International Myeloma Working Group (IMWG) criteria. Progression-free (PFS) and overall survival (OS) were correlated with different PET/CT-derived parameters, such as presence, number and maximum standardized uptake value (SUVmax) of focal myeloma lesions. The impact of extramedullary disease on patient outcome was also assessed.

Results

PET/CT negativity -prior to or following allo-HCT- was a favorable prognostic factor for progression-free and overall survival (both, PFS and OS: pre-HSCT p?<?0.001, post-HCT p?<?0.005). High FDG-uptake (SUVmax?>?6.5) revealed a significantly shortened survival compared to patients with a lower SUVmax (<6.5) (OS, 5.0?±?1.1 m vs. not reached - longest 122.0 m; p?<?0.001). Moreover, our data prove that a higher number (>3) of focal lesions (pre-HCT: both PFS and OS: p?<?0.001; post-HCT PFS: p?<?0.001, OS: p?=?0.139) as well as the presence of extramedullary disease serve as adverse prognostic factors prior to and after allo-HCT. At response assessment after allo-HCT, [18F]FDG-PET/CT had a complementary value in prognostication in addition to IMWG criteria alone.

Conclusion

[18F]FDG-PET/CT before and shortly after allogeneic HCT is a powerful predictor for progression-free and overall survival in MM patients.
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13.

Purpose

The study aims to investigate the role of 18F-alfatide positron emission tomography/computed tomography (PET/CT) in predicting the short-term outcome of concurrent chemoradiotherapy (CCRT) in patients with advanced non-small cell lung cancer (NSCLC).

Methods

Eighteen patients with advanced NSCLC had undergone 18F-alfatide PET/CT scans before CCRT and PET/CT parameters including maximum and mean standard uptake values (SUVmax/SUVmean), peak standard uptake values (SUVpeak) and tumor volume (TVPET and TVCT) were obtained. The SUVmax of tumor and normal tissues (lung, blood pool and muscle) were measured, and their ratios were denoted as T/NT (T/NTlung, T/NTblood and T/NTmuscle). Statistical methods included the Two-example t test, Wilcoxon rank-sum test, Receiver-operating characteristic (ROC) curve analysis and logistic regression analyses.

Results

We found that SUVmax, SUVpeak, T/NTlung, T/NTblood and T/NTmuscle were higher in non-responders than in responders (P?=?0.0024, P?=?0.016, P?<?0.001, P?=?0.003, P?=?0.004). According to ROC curve analysis, the thresholds of SUVmax, SUVpeak, T/NTlung, T/NTblood and T/NTmuscle were 5.65, 4.46, 7.11, 5.41, and 11.75, respectively. The five parameters had high sensitivity, specificity and accuracy in distinguishing non-responders and responders. Multivariate logistic regression analyses showed that T/NTlung was an independent predictor of the short-term outcome of CCRT in patients with advanced NSCLC (P?=?0.032).

Conclusions

18F-alfatide PET/CT may be useful in predicting the short-term outcome of CCRT in patients with advanced NSCLC.
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14.

Aim

The purpose of this study was to investigate the diagnostic performance of 68Ga-PSMA-11 PET/CT in the evaluation of bone metastases in metastatic prostate cancer (PC) patients scheduled for radionuclide therapy in comparison to [18F]sodium fluoride (18F-NaF) PET/CT.

Methods

Sixteen metastatic PC patients with known skeletal metastases, who underwent both 68Ga-PSMA-11 PET/CT and 18F-NaF PET/CT for assessment of metastatic burden prior to radionuclide therapy, were analysed retrospectively. The performance of both tracers was calculated on a lesion-based comparison. Intensity of tracer accumulation of pathologic bone lesions on 18F-NaF PET and 68Ga-PSMA-11 PET was measured with maximum standardized uptake values (SUVmax) and compared to background activity of normal bone. In addition, SUVmax values of PET-positive bone lesions were analysed with respect to morphologic characteristics on CT. Bone metastases were either confirmed by CT or follow-up PET scan.

Results

In contrast to 468 PET-positive lesions suggestive of bone metastases on 18F-NaF PET, only 351 of the lesions were also judged positive on 68Ga-PSMA-11 PET (75.0%). Intensity of tracer accumulation of pathologic skeletal lesions was significantly higher on 18F-NaF PET compared to 68Ga-PSMA-11 PET, showing a median SUVmax of 27.0 and 6.0, respectively (p?<?0.001). Background activity of normal bone was lower on 68Ga-PSMA-11 PET, with a median SUVmax of 1.0 in comparison to 2.7 on 18F-NaF PET; however, tumour to background ratio was significantly higher on 18F-NaF PET (9.8 versus 5.9 on 68Ga-PSMA-11 PET; p?=?0.042). Based on morphologic lesion characterisation on CT, 18F-NaF PET revealed median SUVmax values of 23.6 for osteosclerotic, 35.0 for osteolytic, and 19.0 for lesions not visible on CT, whereas on 68Ga-PSMA-11 PET median SUVmax values of 5.0 in osteosclerotic, 29.5 in osteolytic, and 7.5 in lesions not seen on CT were measured. Intensity of tracer accumulation between18F-NaF PET and 68Ga-PSMA-11 PET was significantly higher in osteosclerotic (p?<?0.001) and lesions not visible on CT (p?=?0.012).

Conclusion

In comparison to 68Ga-PSMA-11 PET/CT, 18F-NaF PET/CT detects a higher number of pathologic bone lesions in advanced stage PC patients scheduled for radionuclide therapy. Our data suggest that 68Ga-PSMA-11 PET should be combined with 18F-NaF PET in PC patients with skeletal metastases for restaging prior to initiation or modification of therapy.
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15.

Purpose

Quantification of myocardial blood flow (MBF) with generator-produced 82Rb is an attractive alternative for centres without an on-site cyclotron. Our aim was to validate 82Rb-measured MBF in relation to that measured using 15O-water, as a tracer 100% of which can be extracted from the circulation even at high flow rates, in healthy control subject and patients with mild coronary artery disease (CAD).

Methods

MBF was measured at rest and during adenosine-induced hyperaemia with 82Rb and 15O-water PET in 33 participants (22 control subjects, aged 30?±?13 years; 11 CAD patients without transmural infarction, aged 60?±?13 years). A one-tissue compartment 82Rb model with ventricular spillover correction was used. The 82Rb flow-dependent extraction rate was derived from 15O-water measurements in a subset of 11 control subjects. Myocardial flow reserve (MFR) was defined as the hyperaemic/rest MBF. Pearson’s correlation r, Bland-Altman 95% limits of agreement (LoA), and Lin’s concordance correlation ρ c (measuring both precision and accuracy) were used.

Results

Over the entire MBF range (0.66–4.7 ml/min/g), concordance was excellent for MBF (r?=?0.90, [82Rb–15O-water] mean difference?±?SD?=?0.04?±?0.66 ml/min/g, LoA?=??1.26 to 1.33 ml/min/g, ρ c?=?0.88) and MFR (range 1.79–5.81, r?=?0.83, mean difference?=?0.14?±?0.58, LoA?=??0.99 to 1.28, ρ c?=?0.82). Hyperaemic MBF was reduced in CAD patients compared with the subset of 11 control subjects (2.53?±?0.74 vs. 3.62?±?0.68 ml/min/g, p?=?0.002, for 15O-water; 2.53?±?1.01 vs. 3.82?±?1.21 ml/min/g, p?=?0.013, for 82Rb) and this was paralleled by a lower MFR (2.65?±?0.62 vs. 3.79?±?0.98, p?=?0.004, for 15O-water; 2.85?±?0.91 vs. 3.88?±?0.91, p?=?0.012, for 82Rb). Myocardial perfusion was homogeneous in 1,114 of 1,122 segments (99.3%) and there were no differences in MBF among the coronary artery territories (p?>?0.31).

Conclusion

Quantification of MBF with 82Rb with a newly derived correction for the nonlinear extraction function was validated against MBF measured using 15O-water in control subjects and patients with mild CAD, where it was found to be accurate at high flow rates. 82Rb-derived MBF estimates seem robust for clinical research, advancing a step further towards its implementation in clinical routine.
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16.

Purpose

Positron emission tomography (PET) using O-(2-18F-fluoroethyl)-L-tyrosine (18F-FET) is a well-established method for the diagnostics of brain tumors. This study investigates reproducibility of 18F-FET uptake kinetics in rat gliomas and the influence of the frequently used dexamethasone (Dex) therapy.

Methods

F98 glioma or 9L gliosarcoma cells were implanted into the striatum of 31 Fischer rats. After 10–11 days of tumor growth, the animals underwent dynamic PET after injection of 18F-FET (baseline). Thereafter, animals were divided into a control group and a group receiving Dex injections, and all animals were reinvestigated 2 days later. Tumor-to-brain ratios (TBR) of 18F-FET uptake (18–61 min p.i.) and the slope of the time-activity-curves (TAC) (18–61 min p.i.) were evaluated using a Volume-of-Interest (VOI) analysis. Data were analyzed by two-way repeated measures ANOVA and reproducibility by the intraclass correlation coefficient (ICC).

Results

The slope of the tumor TACs showed high reproducibility with an ICC of 0.93. A systematic increase of the TBR in the repeated scans was noted (3.7?±?2.8 %; p?<?0.01), and appeared to be related to tumor growth as indicated by a significant correlation of TBR and tumor volume (r?=?0.77; p?<?0.0001). After correction for tumor growth TBR showed high longitudinal stability with an ICC of 0.84. Dex treatment induced a significant decrease of the TBR (?8.2?±?6.1 %; p?<?0.03), but did not influence the slope of the tumor TAC.

Conclusion

TBR of 18F-FET uptake and tracer kinetics in brain tumors showed high longitudinal stability. Dex therapy may induce a minor decrease of the TBR; this needs further investigation.
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17.

Objective

The objective of this study was to determine if clinical dynamic PET/CT imaging with 11C-L-methyl-methionine (11C-MET) in healthy older women can provide an estimate of tissue-level post-absorptive and post-prandial skeletal muscle protein synthesis that is consistent with the more traditional method of calculating fractional synthesis rate (FSR) of muscle protein synthesis from skeletal muscle biopsies obtained during an infusion of L-[ring 13C6] phenylalanine (13C6-Phe).

Methods

Healthy older women (73?±?5 years) completed both dynamic PET/CT imaging with 11C-MET and a stable isotope infusion of 13C6-Phe with biopsies to measure the skeletal muscle protein synthetic response to 25 g of a whey protein supplement. Graphical estimation of the Patlak coefficient Ki from analysis of the dynamic PET/CT images was employed as a measure of incorporation of 11 C-MET in the mid-thigh muscle bundle.

Results

Post-prandial values [mean?±?standard error of the mean (SEM)] were higher than post-absorptive values for both Ki (0.0095?±?0.001 vs. 0.00785?±?0.001 min?1, p?<?0.05) and FSR (0.083?±?0.008 vs. 0.049?±?0.006%/h, p?<?0.001) in response to the whey protein supplement. The percent increase in Ki and FSR in response to the whey protein supplement was significantly correlated (r?=?0.79, p?=?0.015).

Conclusions

Dynamic PET/CT imaging with 11C-MET provides an estimate of the post-prandial anabolic response that is consistent with a traditional, invasive stable isotope, and muscle biopsy approach. These results support the potential future use of 11C-MET imaging as a non-invasive method for assessing conditions affecting skeletal muscle protein synthesis.
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18.

Objectives

To compare the diagnostic performance of 68Ga-DOTATOC PET/MRI and 68Ga-DOTATOC PET/CT in the whole-body staging of patients with neuroendocrine tumours (NET).

Methods

Thirty patients with histopathologically confirmed NET underwent PET/CT and PET/MRI in a single-injection protocol. PET/CT and PET/MRI scans were prospectively evaluated with regard to lesion count, localization, nature (NET/non-NET), and conspicuity (four-point scale). Histopathology and follow-up imaging served as the reference standards. The proportions of NET and non-NET lesions rated correctly were compared using McNemar’s chi-squared test. The Wilcoxon test was used to assess differences in SUVmax and lesion conspicuity. The correlation between the SUVmax for the same lesions from each modality was analysed using Pearson’s correlation coefficient (r).

Results

According to the reference standard, there were 197 lesions (142 NET, 55 non-NET). Lesion-based analysis showed a higher proportion of correctly rated NET lesions on PET/MRI than on PET/CT (90.8% vs. 86.7%, p?=?0.031), whereas on PET/CT there was a higher proportion of correctly rated non-NET lesions (94.5% vs. 83.6%, p?=?0.031). SUVmax was strongly correlated (r?=?0.86; p?<?0.001) and did not differ significantly (p?=?0.35) between the modalities. Overall conspicuity and NET lesion conspicuity were higher on PET/MRI (both p?<?0.01).

Conclusions

Ga-DOTATOC PET/MRI yielded a higher proportion of correctly rated NET lesions and should be regarded as a valuable alternative to 68Ga-DOTATOC PET/CT in whole-body staging of NET patients.

Key Points

? 68 Ga-DOTATOC PET/MRI correctly identified more NET lesions than 68 Ga-DOTATOC PET/CT. ? 68 Ga-DOTATOC PET/MRI provides better NET lesion conspicuity than 68 Ga-DOTATOC PET/CT. ? SUVmax values from the two modalities are strongly correlated and do not differ significantly.
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19.

Purpose

The purpose of our study was to determine the value of 18F-FDG PET before and after induction chemotherapy in patients with oesophageal adenocarcinoma for the early prediction of a poor pathologic response to subsequent preoperative chemoradiotherapy (CRT).

Methods

In 70 consecutive patients receiving a three-step treatment strategy of induction chemotherapy and preoperative chemoradiotherapy for oesophageal adenocarcinoma, 18F-FDG PET scans were performed before and after induction chemotherapy (before preoperative CRT). SUVmax, SUVmean, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) were determined at these two time points. The predictive potential of (the change in) these parameters for a poor pathologic response, progression-free survival (PFS) and overall survival (OS) was assessed.

Results

A poor pathologic response after induction chemotherapy and preoperative CRT was found in 27 patients (39 %). Patients with a poor pathologic response experienced less of a reduction in TLG after induction chemotherapy (p?<?0.01). The change in TLG was predictive for a poor pathologic response at a threshold of ?26 % (sensitivity 67 %, specificity 84 %, accuracy 77 %, PPV 72 %, NPV 80 %), yielding an area-under-the-curve of 0.74 in ROC analysis. Also, patients with a decrease in TLG lower than 26 % had a significantly worse PFS (p?=?0.02), but not OS (p?=?0.18).

Conclusions

18F-FDG PET appears useful to predict a poor pathologic response as well as PFS early after induction chemotherapy in patients with oesophageal adenocarcinoma undergoing a three-step treatment strategy. As such, the early 18F-FDG PET response after induction chemotherapy could aid in individualizing treatment by modification or withdrawal of subsequent preoperative CRT in poor responders.
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20.

Aim

The aim of the study was to compare the kinetic analysis of 18F-labeled choline (FCH) uptake with static analysis and clinicopathological parameters in patients with newly diagnosed prostate cancer (PC).

Materials and methods

Sixty-one patients were included. PSA was performed few days before FCH PET/CT. Gleason scoring (GS) was collected from systematic sextant biopsies. FCH PET/CT consisted in a dual phase: early pelvic list-mode acquisition (from 0 to10 min post-injection) and late whole-body acquisition (60 min post-injection). PC volume of interest was drawn using an adaptative thresholding (40% of the maximal uptake) on the late acquisition and projected onto an early static frame of 10 min and each of the 20 reconstructed frames of 30 s. Kinetic analysis was performed using an imaging-derived plasma input function. Early kinetic parameter (K1 as influx) and static parameters (early SUVmean, late SUVmean, and retention index) were extracted and compared to clinicopathological parameters.

Results

K1 was significantly, but moderately correlated with early SUVmean (r?=?0.57, p?<?0.001) and late SUVmean (r?=?0.43, p?<?0.001). K1, early SUVmean, and late SUVmean were moderately correlated with PSA level (respectively, r?=?0.36, p?=?0.004; r?=?0.67, p?<?0.001; r?=?0.51, p?<?0.001). Concerning GS, K1 was higher for patients with GS?≥?4?+?3 than for patients with GS?<?4?+?3 (median value 0.409 vs 0.272 min??1, p?<?0.001). No significant difference was observed for static parameters.

Conclusions

FCH influx index K1 seems to be related to GS and could be a non-invasive tool to gain further information concerning tumor aggressiveness.
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