Dataset Information

In vivo quantification of hypoxic and metabolic status of NSCLC tumors using [18F]HX4 and [18F]FDG-PET/CT imaging.

ABSTRACT: Increased tumor metabolism and hypoxia are related to poor prognosis in solid tumors, including non-small cell lung cancer (NSCLC). PET imaging is a noninvasive technique that is frequently used to visualize and quantify tumor metabolism and hypoxia. The aim of this study was to perform an extensive comparison of tumor metabolism using 2[(18)F]fluoro-2-deoxy-d-glucose (FDG)-PET and hypoxia using HX4-PET imaging.FDG- and HX4-PET/CT images of 25 patients with NSCLC were coregistered. At a global tumor level, HX4 and FDG parameters were extracted from the gross tumor volume (GTV). The HX4 high-fraction (HX4-HF) and HX4 high-volume (HX4-HV) were defined using a tumor-to-blood ratio > 1.4. For FDG high-fraction (FDG-HF) and FDG high-volume (FDG-HV), a standardized uptake value (SUV) > 50% of SUVmax was used. We evaluated the spatial correlation between HX4 and FDG uptake within the tumor, to quantify the (mis)match between volumes with a high FDG and high HX4 uptake.At a tumor level, significant correlations were observed between FDG and HX4 parameters. For the primary GTV, the HX4-HF was three times smaller compared with the FDG-HF. In 53% of the primary lesions, less than 1 cm(3) of the HX4-HV was outside the FDG-HV; for 37%, this volume was 1.9 to 12 cm(3). Remarkably, a distinct uptake pattern was observed in 11%, with large hypoxic volumes localized outside the FDG-HV.Hypoxic tumor volumes are smaller than metabolic active volumes. Approximately half of the lesions showed a good spatial correlation between the PET tracers. In the other cases, a (partial) mismatch was observed. The addition of HX4-PET imaging has the potential to individualize patient treatment.

SUBMITTER: Zegers CM

PROVIDER: S-EPMC5228298 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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In vivo quantification of hypoxic and metabolic status of NSCLC tumors using [18F]HX4 and [18F]FDG-PET/CT imaging.

Zegers Catharina M L CM van Elmpt Wouter W Reymen Bart B Even Aniek J G AJ Troost Esther G C EG Ollers Michel C MC Hoebers Frank J P FJ Houben Ruud M A RM Eriksson Jonas J Windhorst Albert D AD Mottaghy Felix M FM De Ruysscher Dirk D Lambin Philippe P

Clinical cancer research : an official journal of the American Association for Cancer Research 20141014 24

<h4>Purpose</h4>Increased tumor metabolism and hypoxia are related to poor prognosis in solid tumors, including non-small cell lung cancer (NSCLC). PET imaging is a noninvasive technique that is frequently used to visualize and quantify tumor metabolism and hypoxia. The aim of this study was to perform an extensive comparison of tumor metabolism using 2[(18)F]fluoro-2-deoxy-d-glucose (FDG)-PET and hypoxia using HX4-PET imaging.<h4>Experimental design</h4>FDG- and HX4-PET/CT images of 25 patients ...[more]

PMID: 25316821

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Project description:INTRODUCTION:Only a subgroup of non-small cell lung cancer (NSCLC) patients benefit from treatment using epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) such as afatinib. Tumour uptake of [18F]afatinib using positron emission tomography (PET) may identify those patients that respond to afatinib therapy. Therefore, the aim of this study was to find the optimal tracer kinetic model for quantification of [18F]afatinib uptake in NSCLC tumours. METHODS:[18F]Afatinib PET scans were performed in 10 NSCLC patients. The first patient was scanned for the purpose of dosimetry. Subsequent patients underwent a 20-min dynamic [15O]H2O PET scan (370 MBq) followed by a dynamic [18F]afatinib PET scan (342 ± 24 MBq) of 60 or 90 min. Using the Akaike information criterion (AIC), three pharmacokinetic plasma input models were evaluated with both metabolite-corrected sampler-based input and image-derived (IDIF) input functions in combination with discrete blood samples. Correlation analysis of arterial on-line sampling versus IDIF was performed. In addition, perfusion dependency and simplified measures were assessed. RESULTS:Ten patients were included. The injected activity of [18F]afatinib was 341 ± 37 MBq. Fifteen tumours could be identified in the field of view of the scanner. Based on AIC, tumour kinetics were best described using an irreversible two-tissue compartment model and a metabolite-corrected sampler-based input function (Akaike 50%). Correlation of plasma-based input functions with metabolite-corrected IDIF was very strong (r2 = 0.93). The preferred simplified uptake parameter was the tumour-to-blood ratio over the 60- to 90-min time interval (TBR60-90). Tumour uptake of [18F]afatinib was independent of perfusion. CONCLUSION:The preferred pharmacokinetic model for quantifying [18F]afatinib uptake in NSCLC tumours was the 2T3K_vb model. TBR60-90 showed excellent correlation with this model and is the best candidate simplified method. TRIAL REGISTRATION:https://eudract.ema.europa.eu/ nr 2012-002849-38.

Project description:UnlabelledFor brown adipose tissue (BAT) to be effective at consuming calories, its blood flow must increase enough to provide sufficient fuel to sustain energy expenditure and also transfer the heat created to avoid thermal injury. Here we used a combination of human and rodent models to assess changes in BAT blood flow and glucose utilization.Methods(99m)Tc-methoxyisobutylisonitrile (MIBI) SPECT (n = 7) and SPECT/CT (n = 74) scans done in adult humans for parathyroid imaging were reviewed for uptake in regions consistent with human BAT. Site-directed biopsies of subcutaneous and deep neck fat were obtained for electron microscopy and gene expression profiling. In mice, tissue perfusion was measured with (99m)Tc-MIBI (n = 16) and glucose uptake with (18)F-FDG (n = 16). Animals were kept fasting overnight, anesthetized with pentobarbital, and given intraperitoneally either the β3-adrenergic receptor agonist CL-316,243, 1 mg/kg (n = 8), or saline (n = 8) followed by radiotracer injection 5 min later. After 120 min, the mice were imaged using SPECT/CT or PET/CT. Vital signs were recorded over 30 min during the imaging. BAT, white adipose tissue (WAT), muscle, liver, and heart were resected, and tissue uptake of both (99m)Tc-MIBI and (18)F-FDG was quantified by percentage injected dose per gram of tissue and normalized to total body weight.ResultsIn 5.4% of patients (4/74), (99m)Tc-MIBI SPECT/CT showed increased retention in cervical and supraclavicular fat that displayed multilocular lipid droplets, dense capillary investment, and a high concentration of ovoid mitochondria. Expression levels of the tissue-specific uncoupling protein-1 were 180 times higher in BAT than in subcutaneous WAT (P < 0.001). In mice, BAT tissue perfusion increased by 61% (P < 0.01), with no significant changes in blood flow to WAT, muscle, heart, or liver. CL-316,243 increased glucose uptake in BAT even more, by 440% (P < 0.01).ConclusionPharmacologic activation of BAT requires increased blood flow to deliver glucose and oxygen for thermogenesis. However, the glucose consumption far exceeds the vascular response. These findings demonstrate that activated BAT increases glucose uptake beyond what might occur by increased blood flow alone and suggest that activated BAT likely uses glucose for nonthermogenic purposes.

Project description:BACKGROUND:Total metabolic active tumour volume (TMATV) and total tumour burden (TTB) are increasingly studied as prognostic and predictive factors in non-small cell lung cancer (NSCLC) patients. In this study, we investigated the repeatability of TMATV and TTB as function of uptake interval, positron emission tomography/computed tomography (PET/CT) image reconstruction settings, and lesion delineation method. We used six lesion delineation methods, four direct PET image-derived delineations and two based on a majority vote approach, i.e. intersection between two or more delineations (MV2) and between three or more delineations (MV3). To evaluate the accuracy of those methods, they were compared with a reference delineation obtained from the consensus of the segmentations performed by three experienced observers. Ten NSCLC patients underwent two baseline whole-body [18F]2-Fluoro-2-deoxy-2-D-glucose ([18F]FDG) PET/CT studies on separate days, within 3 days. Two scans were obtained on each day at 60 and 90?min post-injection to assess the influence of tracer uptake interval. PET/CT images were reconstructed following the European Association of Nuclear Medicine Research Ltd. (EARL) compliant settings and with point-spread-function (PSF) modelling. Repeatability between the measurements of each day was determined and the influence of uptake interval, reconstruction settings, and lesion delineation method was assessed using the generalized estimating equations model. RESULTS:Based on the Jaccard index with the reference delineation, the MV2 lesion delineation method was the most successful method for automated lesion segmentation. The best overall repeatability (lowest repeatability coefficient, RC) was found for TTB from 90?min of tracer uptake scans reconstructed with EARL compliant settings and delineated with 41% of lesion's maximum SUV method (RC?=?11%). In most cases, TMATV and TTB repeatability were not significantly affected by changes in tracer uptake time or reconstruction settings. However, some lesion delineation methods had significantly different repeatability when applied to the same images. CONCLUSIONS:This study suggests that under some circumstances TMATV and TTB repeatability are significantly affected by the lesion delineation method used. Performing the delineation with a majority vote approach improves reliability and does not hamper repeatability, regardless of acquisition and reconstruction settings. It is therefore concluded that by using a majority vote based tumour segmentation approach, TMATV and TTB in NSCLC patients can be measured with high reliability and precision.

Dataset Information

In vivo quantification of hypoxic and metabolic status of NSCLC tumors using [18F]HX4 and [18F]FDG-PET/CT imaging.

Publications

In vivo quantification of hypoxic and metabolic status of NSCLC tumors using [18F]HX4 and [18F]FDG-PET/CT imaging.

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