Reproducibility of 18F-fluoromisonidazole intratumour distribution in non-small cell lung cancer.
Ontology highlight
ABSTRACT:
SUBMITTER: Grkovski M
PROVIDER: S-EPMC5099292 | biostudies-literature | 2016 Dec
REPOSITORIES: biostudies-literature
Publications
Reproducibility of <sup>18</sup>F-fluoromisonidazole intratumour distribution in non-small cell lung cancer.
Grkovski Milan M Schwartz Jazmin J Rimner Andreas A Schöder Heiko H Carlin Sean D SD Zanzonico Pat B PB Humm John L JL Nehmeh Sadek A SA
EJNMMI research 20161107 1
<h4>Background</h4>Hypoxic tumours exhibit increased resistance to radiation, chemical, and immune therapies. <sup>18</sup>F-fluoromisonidazole (FMISO) positron emission tomography (PET) is a non-invasive, quantitative imaging technique used to evaluate the presence and spatial distribution of tumour hypoxia. To facilitate the use of FMISO PET for identification of individuals likely to benefit from hypoxia-targeted treatments, we investigated the reproducibility of FMISO PET spatiotemporal intr ...[more]
Similar Datasets
Project description:BACKGROUND:To determine the relative abilities of compartment models to describe time-courses of 18F-fluoromisonidazole (FMISO) tumor uptake in patients with advanced stage non-small cell lung cancer (NSCLC) imaged using dynamic positron emission tomography (dPET), and study correlations between values of the blood flow-related parameter K1 obtained from fits of the models and an independent blood flow measure obtained from perfusion CT (pCT). NSCLC patients had a 45-min dynamic FMISO PET/CT scan followed by two static PET/CT acquisitions at 2 and 4-h post-injection. Perfusion CT scanning was then performed consisting of a 45-s cine CT. Reversible and irreversible two-, three- and four-tissue compartment models were fitted to 30 time-activity-curves (TACs) obtained for 15 whole tumor structures in 9 patients, each imaged twice. Descriptions of the TACs provided by the models were compared using the Akaike and Bayesian information criteria (AIC and BIC) and leave-one-out cross-validation. The precision with which fitted model parameters estimated ground-truth uptake kinetics was determined using statistical simulation techniques. Blood flow from pCT was correlated with K1 from PET kinetic models in addition to FMISO uptake levels. RESULTS:An irreversible three-tissue compartment model provided the best description of whole tumor FMISO uptake time-courses according to AIC, BIC, and cross-validation scores totaled across the TACs. The simulation study indicated that this model also provided more precise estimates of FMISO uptake kinetics than other two- and three-tissue models. The K1 values obtained from fits of the irreversible three-tissue model correlated strongly with independent blood flow measurements obtained from pCT (Pearson r coefficient = 0.81). The correlation from the irreversible three-tissue model (r?=?0.81) was stronger than that from than K1 values obtained from fits of a two-tissue compartment model (r?=?0.68), or FMISO uptake levels in static images taken at time-points from tracer injection through to 4 h later (maximum at 2 min, r?=?0.70). CONCLUSIONS:Time-courses of whole tumor FMISO uptake by advanced stage NSCLC are described best by an irreversible three-tissue compartment model. The K1 values obtained from fits of the irreversible three-tissue model correlated strongly with independent blood flow measurements obtained from perfusion CT (r?=?0.81).
| S-EPMC6070455 | biostudies-literature
Project description:BACKGROUND:There is an increasing interest in developing predictive biomarkers of tissue hypoxia using functional imaging for personalised radiotherapy in patients with rectal cancer that are considered for neoadjuvant chemoradiotherapy (CRT). The study explores [18F]fluoromisonidazole ([18F]FMISO) positron emission tomography (PET) scans for predicting clinical response in rectal cancer patients receiving neoadjuvant CRT. METHODS:Patients with biopsy-proven rectal adenocarcinoma were imaged at 0-45 min, 2 and 4 h, at baseline and after 8-10 fractions of CRT (week 2). The first 6 patients did not receive an enema (the non-enema group) and the last 4 patients received an enema before PET-CT scan (the enema group). [18F]FMISO production failed on 2 occasions. Static PET images at 4 h were analysed using tumour-to-muscle (T:M) SUVmax and tumour-to-blood (T:B) SUVmax. The 0-45 min dynamic PET scans were analysed using Casciari model to report hypoxia and perfusion. Akaike information criteria (AIC) were used to compare data fittings for different pharmacokinetic models. Pathological tumour regression grade was scored using American Joint Committee on Cancer (AJCC) 7.0. Shapiro-Wilk test was used to evaluate the normality of the data. RESULTS:Five out of eleven (5/11) patients were classed as good responders (AJCC 0/1 or good clinical response) and 6/11 as poor responders (AJCC 2/3 or poor clinical response). The median T:M SUVmax was 2.14 (IQR 0.58) at baseline and 1.30 (IQR 0.19) at week 2, and the corresponding median tumour hypoxia volume was 1.08 (IQR 1.31) cm3 and 0 (IQR 0.15) cm3, respectively. The median T:B SUVmax was 2.46 (IQR 1.50) at baseline and 1.61 (IQR 0.14) at week 2, and the corresponding median tumour hypoxia volume was 5.68 (IQR 5.86) cm3 and 0.76 (IQR 0.78) cm3, respectively. For 0-45 min tumour modelling, the median hypoxia was 0.92 (IQR 0.41) min-1 at baseline and 0.70 (IQR 0.10) min-1 at week 2. The median perfusion was 4.10 (IQR 1.71) ml g-1 min-1 at baseline and 2.48 (IQR 3.62) ml g-1 min-1 at week 2. In 9/11 patients with both PET scans, tumour perfusion decreased in non-responders and increased in responders except in one patient. None of the changes in other PET parameters showed any clear trend with clinical outcome. CONCLUSIONS:This pilot study with small number of datasets revealed significant challenges in delivery and interpretation of [18F]FMISO PET scans of rectal cancer. There are two principal problems namely spill-in from non-tumour tracer activity from rectal and bladder contents. Emphasis should be made on reducing spill-in effects from the bladder to improve data quality. This preliminary study has shown fundamental difficulties in the interpretation of [18F]FMISO PET scans for rectal cancer, limiting its clinical applicability.
| S-EPMC5607050 | biostudies-literature
Project description:Hypoxic tumors exhibit increased resistance to radiation, chemical, and immune therapies. 18F-fluoromisonidazole (18F-FMISO) PET is a noninvasive, quantitative imaging technique used to evaluate the magnitude and spatial distribution of tumor hypoxia. In this study, pharmacokinetic analysis (PKA) of 18F-FMISO dynamic PET extended to 3 h after injection is reported for the first time, to our knowledge, in stage III-IV non-small cell lung cancer (NSCLC) patients. Methods: Sixteen patients diagnosed with NSCLC underwent 2 PET/CT scans (1-3 d apart) before radiation therapy: a 3-min static 18 F-FDG and a dynamic 18F-FMISO scan lasting 168 ± 15 min. The latter data were acquired in 3 serial PET/CT dynamic imaging sessions, registered with each other and analyzed using pharmacokinetic modeling software. PKA was performed using a 2-tissue, 3-compartment irreversible model, and kinetic parameters were estimated for the volumes of interest determined using coregistered 18F-FDG images for both the volume of interest-averaged and the voxelwise time-activity curves for each patient's lesions, normal lung, and muscle. Results: We derived average values of 18F-FMISO kinetic parameters for NSCLC lesions as well as for normal lung and muscle. We also investigated the correlation between the trapping rate (k3) and delivery rate (K1), influx rate (Ki ) constants, and tissue-to-blood activity concentration ratios (TBRs) for all tissues. Lesions had trapping rates 1.6 times larger, on average, than those of normal lung and 4.4 times larger than those in muscle. Additionally, for almost all cases, k3 and Ki had a significant strong correlation for all tissue types. The TBR-k3 correlation was less straightforward, showing a moderate to strong correlation for only 41% of lesions. Finally, K1-k3 voxelwise correlations for tumors were varied, but negative for 76% of lesions, globally exhibiting a weak inverse relationship (average R = -0.23 ± 0.39). However, both normal tissue types exhibited significant positive correlations for more than 60% of patients, with 41% having moderate to strong correlations (R > 0.5). Conclusion: All lesions showed distinct 18F-FMISO uptake. Variable 18F-FMISO delivery was observed across lesions, as indicated by the variable values of the kinetic rate constant K1 Except for 3 cases, some degree of hypoxia was apparent in all lesions based on their nonzero k3 values.
| S-EPMC5450365 | biostudies-literature
Project description:Epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) are a response to EGFR-tyrosine kinase inhibitor. However, a lack of sufficient tumor tissue has been a limitation for determining EGFR mutation status in clinical practice. The objective of this study was to predict EGFR mutation status in NSCLC patients based on a model including maximum standardized uptake value (SUVmax) and clinical features.We retrospectively reviewed NSCLC patients undergoing EGFR mutation testing and pretreatment positron emission tomography/computed tomography between March 2009 and December 2013. The relationships of EGFR mutations with both SUVmax and patient characteristics were evaluated, and a multivariate logistic regression analysis was performed. The model was assessed by area under the receiver-operating characteristic curve (AUC) and was prospectively validated during January to June 2014.Three hundred and sixteen patients meeting the criteria were enrolled for model construction. The SUVmax values were significantly lower for EGFR mutations (mean, 9.5 ± 5.74) than for EGFR wild-type (mean, 12.7 ± 6.43; P < 0.001). ROC curve analysis showed that the SUVmax cutoff point was 8.1, for which the AUC was 0.65 (95% confidence interval [CI], 0.60-0.72). In addition, multivariate analysis also showed that low SUVmax (≤8.1) was a predictor of EGFR mutations, for which the AUC was 0.77, combining nonsmoking history and primary tumor size (≤5 cm). Eighty-five patients were enrolled to validate the predictive model, and the overall accuracy, sensitivity, and specificity were 77.6%, 64.6% (95% CI 40.7-82.8), and 82.5% (95% CI 70.9-91.0), respectively.The specific FDG uptake value could be considered to effectively predict EGFR mutation status of NSCLC patients by considering smoking history and primary tumor size when genetic tests are not available.
| S-EPMC5265876 | biostudies-literature
Project description:This is a clinical study to compare noninvasive hypoxia imaging using 18F-fluoroerythronitroimidazole (18F-FETNIM) and 18F-fluoromisonidazole (18F-FMISO) positron emission tomography/computed tomography (PET/CT) in patients with inoperable stages III-IV lung cancer.A total of forty-two patients with inoperable stages III-IV lung cancer underwent 18F-FETNIM PET/CT (n = 18) and 18F-FMISO PET/CT (n = 24) before chemo/radiation therapy. The standard uptake values (SUVs) of malignant and normal tissues depict 18F-FETNIM PET/CT and 18F-FMISO PET/CT uptake. Tumor-to-blood ratios (T/B) were used to quantify hypoxia.All patients with lung cancer underwent 18F-FETNIM PET/CT and 18F-FMISO PET/CT successfully. Compared to 18F-FMISO, 18F-FETNIM showed similar uptake in muscle, thyroid, spleen, pancreas, heart, lung and different uptake in blood, liver, and kidney. Significantly higher SUV and T/B ratio with 18F-FMISO (2.56±0.77, 1.98±0.54), as compared to 18F-FETNIM (2.12±0.56, 1.42±0.33) were seen in tumor, P = 0.022, <0.001. For the patients with different histopathological subtypes, no significant difference of SUV (or T/B ratio) was observed both in 18F-FMISO and 18F-FETNIM in tumor. A significantly different SUV (or T/B ratio) was detected between < = 2cm, 2~5cm, and >5cm groups in 18F-FMISO PET/CT, P = 0.015 (or P = 0.029), whereas no difference was detected in 18F-FMISO PET/CT, P = 0.446 (or P = 0.707). Both 18F-FETNIM and 18F-FMISO showed significantly higher SUVs (or T/B ratios) in stage IV than stage III, P = 0.021, 0.013 (or P = 0.032, 0.02).18F-FMISO showed significantly higher uptake than 18F-FETNIM in tumor/non-tumor ratio and might be a better hypoxia tracer in lung cancer.
| S-EPMC4913930 | biostudies-literature
Project description:Platelets play a multifaceted role in cancer progression and metastasis. Mean platelet volume (MPV) and platelet distribution width (PDW) are commonly used platelet parameters from routine blood test. The aim of the present study was to investigate the correlation between platelet indices and prognosis in patients with non-small cell lung cancer (NSCLC). A total of 270 patients who were diagnosed with NSCLC between January 2009 and December 2009 were retrospectively analyzed. Patients' characteristics and hematologic tests data at initial diagnosis were collected. The overall survival rate was estimated using Kaplan-Meier method. The prognostic analysis was carried out with univariate and multivariate Cox regressions model. Reduced PDW was significantly correlated with T stage, N stage, TNM stage, and histological type of the disease. Moreover, survival analysis showed that the overall survival of patients with PDW???16.3% was significantly longer than that of those with PDW?<?16.3% (P?<?0.001). In multivariate Cox regression model, age, sex, TNM stage, and PDW were identified as independent prognostic factors for overall survival (for PDW, P?<?0.001). In conclusion, reduced PDW is an unfavorable predictive factor of NSCLC patient survival. Further studies are warranted.
| S-EPMC5471191 | biostudies-literature
Project description:PurposeThe aim of this study was to determine the relative abilities of compartment models to describe time-courses of 18 F-fluoromisonidazole (FMISO) uptake in tumor voxels of patients with non-small cell lung cancer (NSCLC) imaged using dynamic positron emission tomography. Also to use fits of the best-performing model to investigate changes in fitted rate-constants with distance from the tumor edge.MethodsReversible and irreversible two- and three-tissue compartment models were fitted to 24 662 individual voxel time activity curves (TACs) obtained from tumors in nine patients, each imaged twice. Descriptions of the TACs provided by the models were compared using the Akaike and Bayesian information criteria (AIC and BIC). Two different models (two- and three-tissue) were fitted to 30 measured voxel TACs to provide ground-truth TACs for a statistical simulation study. Appropriately scaled noise was added to each of the resulting ground-truth TACs, generating 1000 simulated noisy TACs for each ground-truth TAC. The simulation study was carried out to provide estimates of the accuracy and precision with which parameter values are determined, the estimates being obtained for both assumptions about the ground-truth kinetics. A BIC clustering technique was used to group the fitted rate-constants, taking into consideration the underlying uncertainties on the fitted rate-constants. Voxels were also categorized according to their distance from the tumor edge.ResultsFor uptake time-courses of individual voxels an irreversible two-tissue compartment model was found to be most precise. The simulation study indicated that this model had a one standard deviation precision of 39% for tumor fractional blood volumes and 37% for the FMISO binding rate-constant. Weighted means of fitted FMISO binding rate-constants of voxels in all tumors rose significantly with increasing distance from the tumor edge, whereas fitted fractional blood volumes fell significantly. When grouped using the BIC clustering, many centrally located voxels had high-fitted FMISO binding rate-constants and low rate-constants for tracer flow between the vasculature and tumor, both indicative of hypoxia. Nevertheless, many of these voxels had tumor-to-blood (TBR) values lower than the 1.4 level commonly expected for hypoxic tissues, possibly due to the low rate-constants for tracer flow between the vasculature and tumor cells in these voxels.ConclusionsTime-courses of FMISO uptake in NSCLC tumor voxels are best analyzed using an irreversible two-tissue compartment model, fits of which provide more precise parameter values than those of a three-tissue model. Changes in fitted model parameter values indicate that levels of hypoxia rise with increasing distance from tumor edges. The average FMISO binding rate-constant is higher for voxels in tumor centers than in the next tumor layer out, but the average value of the more simplistic TBR metric is lower in tumor centers. For both metrics, higher values might be considered indicative of hypoxia, and the mismatch in this case is likely to be due to poor perfusion at the tumor center. Kinetics analysis of dynamic PET images may therefore provide more accurate measures of the hypoxic status of such regions than the simpler TBR metric, a hypothesis we are presently exploring in a study of tumor imaging versus histopathology.
| S-EPMC5600259 | biostudies-literature
Project description:The identification of surgical non-small cell lung cancer (NSCLC) patients with poor prognosis is a priority in clinical oncology because of their high 5-year mortality. This meta-analysis explored the prognostic value of maximal standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) on disease-free survival (DFS) and overall survival (OS) in surgical NSCLC patients.MEDLINE, EMBASE and Cochrane Libraries were systematically searched until August 1, 2015. Prospective or retrospective studies that evaluated the prognostic roles of preoperative 18F-FDG PET/CT with complete DFS and OS data in surgical NSCLC patients were included. The impact of SUVmax, MTV or TLG on survival was measured using hazard ratios (HR). Sub-group analyses were performed based on disease stage, pathological classification, surgery only and cut-off values.Thirty-six studies comprised of 5807 patients were included. The combined HRs for DFS were 2.74 (95%CI 2.33-3.24, unadjusted) and 2.43 (95%CI: 1.76-3.36, adjusted) for SUVmax, 2.27 (95%CI 1.77-2.90, unadjusted) and 2.49 (95%CI 1.23-5.04, adjusted) for MTV, and 2.46 (95%CI 1.91-3.17, unadjusted) and 2.97 (95%CI 1.68-5.28, adjusted) for TLG. The pooled HRs for OS were 2.54 (95%CI 1.86-3.49, unadjusted) and 1.52 (95%CI 1.16-2.00, adjusted) for SUVmax, 2.07 (95%CI 1.16-3.69, unadjusted) and 1.91 (95%CI 1.13-3.22, adjusted) for MTV, and 2.47 (95%CI 1.38-4.43, unadjusted) and 1.94 (95%CI 1.12-3.33, adjusted) for TLG. Begg's test detected publication bias, the trim and fill procedure was performed, and similar HRs were obtained. The prognostic role of SUVmax, MTV and TLG remained similar in the sub-group analyses.High values of SUVmax, MTV and TLG predicted a higher risk of recurrence or death in patients with surgical NSCLC. We suggest the use of FDG PET/CT to select patients who are at high risk of disease recurrence or death and may benefit from aggressive treatments.
| S-EPMC4699812 | biostudies-literature
Project description:PurposeTexture indices (TI) calculated from 18F-FDG PET tumor images show promise for predicting response to therapy and survival. Their calculation involves a resampling of standardized uptake values (SUV) within the tumor. This resampling can be performed differently and significantly impacts the TI values. Our aim was to investigate how the resampling approach affects the ability of TI to reflect tissue-specific pattern of metabolic activity.Methods18F-FDG PET were acquired for 48 naïve-treatment patients with non-small cell lung cancer and for a uniform phantom. We studied 7 TI, SUVmax and metabolic volume (MV) in the phantom, tumors and healthy tissue using the usual relative resampling (RR) method and an absolute resampling (AR) method. The differences in TI values between tissue types and cancer subtypes were investigated using Wilcoxon's tests.ResultsMost RR-based TI were highly correlated with MV for tumors less than 60 mL (Spearman correlation coefficient r between 0.74 and 1), while this correlation was reduced for AR-based TI (r between 0.06 and 0.27 except for RLNU where r = 0.91). Most AR-based TI were significantly different between tumor and healthy tissues (pvalues <0.01 for all 7 TI) and between cancer subtypes (pvalues<0.05 for 6 TI). Healthy tissue and adenocarcinomas exhibited more homogeneous texture than tumor tissue and squamous cell carcinomas respectively.ConclusionTI computed using an AR method vary as a function of the tissue type and cancer subtype more than the TI involving the usual RR method. AR-based TI might be useful for tumor characterization.
| S-EPMC4682929 | biostudies-literature
Project description:BACKGROUND:[18F]HX4 is a promising new PET tracer developed to identify hypoxic areas in tumor tissue. This study analyzes [18F]HX4 kinetics and assesses the performance of simplified methods for quantification of [18F]HX4 uptake. To this end, eight patients with non-small cell lung cancer received dynamic PET scans at three different time points (0, 120, and 240 min) after injection of 426?±?72 MBq [18F]HX4, each lasting 30 min. Several compartment models were fitted to time activity curves (TAC) derived from various areas within tumor tissue using image-derived input functions. RESULTS:Best fits were obtained using the reversible two-tissue compartment model with blood volume parameter (2T4k+VB). Simplified measures correlated well with VT estimates (tumor-to-blood ratio (TBr) R 2?=?0.96, tumor-to-muscle ratio R 2?=?0.94, standardized uptake value R 2?=?0.89). CONCLUSIONS:[18F]HX4 shows reversible kinetics in tumor tissue: 2T4k+VB. TBr based on static imaging at 2 or 4 h can be used for quantification of [18F]HX4 uptake.
| S-EPMC5153396 | biostudies-literature