Pulmonary 18F-FDG uptake helps refine current risk stratification in idiopathic pulmonary fibrosis (IPF).

PURPOSE: There is a lack of prognostic biomarkers in idiopathic pulmonary fibrosis (IPF) patients. The objective of this study is to investigate the potential of 18F-FDG-PET/ CT to predict mortality in IPF. METHODS: A total of 113 IPF patients (93 males, 20 females, mean age ± SD: 70 ± 9 years) were prospectively recruited for 18F-FDG-PET/CT. The overall maximum pulmonary uptake of 18F-FDG (SUVmax), the minimum pulmonary uptake or background lung activity (SUVmin), and target-to-background (SUVmax/ SUVmin) ratio (TBR) were quantified using routine region-of-interest analysis. Kaplan-Meier analysis was used to identify associations of PET measurements with mortality. We also compared PET associations with IPF mortality with the established GAP (gender age and physiology) scoring system. Cox analysis assessed the independence of the significant PET measurement(s) from GAP score. We investigated synergisms between pulmonary 18F-FDG-PET measurements and GAP score for risk stratification in IPF patients. RESULTS: During a mean follow-up of 29 months, there were 54 deaths. The mean TBR ± SD was 5.6 ± 2.7. Mortality was associated with high pulmonary TBR (p = 0.009), low forced vital capacity (FVC; p = 0.001), low transfer factor (TLCO; p < 0.001), high GAP index (p = 0.003), and high GAP stage (p = 0.003). Stepwise forward-Wald-Cox analysis revealed that the pulmonary TBR was independent of GAP classification (p = 0.010). The median survival in IPF patients with a TBR < 4.9 was 71 months, whilst in those with TBR > 4.9 was 24 months. Combining PET data with GAP data ("PET modified GAP score") refined the ability to predict mortality. CONCLUSIONS: A high pulmonary TBR is independently associated with increased risk of mortality in IPF patients.

The Impact of 68Ga-DOTATATE PET/CT Imaging on Management of Patients with Neuroendocrine Tumors: Experience from a National Referral Center in the United Kingdom.

UNLABELLED: (68)Ga-DOTATATE PET/CT scanning is a widely accepted method for imaging of neuroendocrine tumors. This cross-sectional study was performed to review the first 8 y of patient data from a large (68)Ga-DOTATATE PET/CT database in order to establish the impact of the modality on patient treatment and survival. METHODS: Demographic data, clinical outcome, survival, and change in management after (68)Ga-DOTATATE PET/CT were evaluated. RESULTS: Between May 2005 and August 2013, 1,258 (68)Ga-DOTATATE PET/CT scans were obtained in 728 patients with confirmed or suspected neuroendocrine tumors. In most patients, the primary site was located in the midgut (26.4%). Analysis of NET grading in patients with known histopathologic data revealed that 35.7% had NET grade G1, 12.2% G2, and 8.7% G3. The most common indications for (68)Ga-DOTATATE PET/CT were follow-up (24.4%) and initial tumor staging (23.4%). Of the 1,258 (68)Ga-DOTATATE PET/CT scans completed, 75.7% were positive and 24.3% negative; there were 14 false-positive and 29 false-negative scans. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 97%, 95.1%, 96.6%, 98.5%, and 90.4%, respectively. In 40.9% of patients, the treatment plan was changed after the scans, owing mainly to new, unexpected findings. Statistically significant differences in survival were shown between patients with G1, G2, and G3 grade tumors (P < 0.0001) and also between patients with bone metastasis versus patients with soft-tissue metastasis (P < 0.0001). CONCLUSION: (68)Ga-DOTATATE PET/CT scanning is safe and influences management in a large proportion of patients. Prognosis was dependent on tumor grade, and the presence of bone metastasis was associated with worse overall survival.

Simultaneous PET-MRI Studies of the Concordance of Atrophy and Hypometabolism in Syndromic Variants of Alzheimer's Disease and Frontotemporal Dementia: An Extended Case Series.

BACKGROUND: Simultaneous PET-MRI is used to compare patterns of cerebral hypometabolism and atrophy in six different dementia syndromes. OBJECTIVES: The primary objective was to conduct an initial exploratory study regarding the concordance of atrophy and hypometabolism in syndromic variants of Alzheimer's disease (AD) and frontotemporal dementia (FTD). The secondary objective was to determine the effect of image analysis methods on determination of atrophy and hypometabolism. METHOD: PET and MRI data were acquired simultaneously on 24 subjects with six variants of AD and FTD (n = 4 per group). Atrophy was rated visually and also quantified with measures of cortical thickness. Hypometabolism was rated visually and also quantified using atlas- and SPM-based approaches. Concordance was measured using weighted Cohen's kappa. RESULTS: Atrophy-hypometabolism concordance differed markedly between patient groups; kappa scores ranged from 0.13 (nonfluent/agrammatic variant of primary progressive aphasia, nfvPPA) to 0.49 (posterior cortical variant of AD, PCA). Heterogeneity was also observed within groups; the confidence intervals of kappa scores ranging from 0-0.25 for PCA to 0.29-0.61 for nfvPPA. More widespread MRI and PET changes were identified using quantitative methods than on visual rating. CONCLUSION: The marked differences in concordance identified in this initial study may reflect differences in the molecular pathologies underlying AD and FTD syndromic variants but also operational differences in the methods used to diagnose these syndromes. The superior ability of quantitative methodologies to detect changes on PET and MRI, if confirmed on larger cohorts, may favor their usage over qualitative visual inspection in future clinical diagnostic practice.

The utility of 18F-fluorodeoxyglucose PET (FDG PET) in epilepsy surgery.

PURPOSE: To investigate the utility of 18F-fluorodeoxyglucose Positron Emission Tomography (FDG PET) in helping decision making for epilepsy surgery. METHODS: All patients with medically refractory focal epilepsy and MRI that was normal or discordant with clinical and EEG data underwent FDG PET. FDG PET scans were reported by two investigators blinded to clinical data using visual assessment aided by the semiquantitative assessment. All clinical, MRI and FDG PET data were reviewed in the multidisciplinary patient management conferences for the localization and further decisions, which were recorded in the electronic database. For this study, we reviewed the charts of all these patients to decide the usefulness of PET in further decision making. FDG PET was considered to be useful if led directly to surgery, helped in planning intracranial EEG or helped in excluding patients from further evaluation. RESULTS: 194 consecutive adult patients (median age, 32.5 years) underwent FDG PET; 158 had normal MRI, 12 had subtle MRI abnormalities and 24 had discordant non-invasive data. Final localization was temporal lobe epilepsy (TLE, n=64), frontal lobe epilepsy (FLE, n=66), temporal-plus epilepsy (n=26) and other extratemporal lobe epilepsies (ETE, n=38). PET scans were normal in 72 (37%) patients, showed unifocal hypometabolism in 98 (50.5%) and bilateral hypometabolism in 24 (12%) patients. The TLE group had a higher proportion of abnormal PET scans (67%) than FLE (52%) and ETE (61%). PET data were useful in 103 (53%) patients, more in TLE (63%) than FLE (38%) or ETE (50%). It led directly to surgery in 12 (6%) cases, helped in planning intracranial EEG in 67 (35%) patients and excluded 24 (12%) patients from further evaluation. Focal hypometabolism on FDG PET increased the odds of being selected for surgery or intracranial EEG by five fold [odds ratio, 5.1 (2.8-9.4); p<0.0001]. CONCLUSIONS: FDG PET scan can help decision making in 53% of presurgical patients with normal or discordant MRI. PET findings need to be evaluated in conjunction with other data.

Motor and cognitive advantages persist 12 months after exenatide exposure in Parkinson's disease.

BACKGROUND: Data from an open label randomised controlled trial have suggested possible advantages on both motor and non-motor measures in patients with Parkinson's disease following 12 months exposure to exenatide. OBJECTIVE: Continued follow up of these same patients was performed to investigate whether these possible advantages persisted in the prolonged absence of this medication. METHODS: All participants from an open label, randomised controlled trial of exenatide as a treatment for Parkinson's disease, were invited for a further follow up assessment at the UCL Institute of Neurology. This visit included all 20 individuals who had previously completed twelve months exposure to exenatide 10ug bd and the 24 individuals who had acted as randomised controls. Motor severity of PD was compared after overnight withdrawal of conventional PD medication using blinded video assessment of the MDS-UPDRS, together with several non-motor tests. This assessment was thus 24 months after their original baseline visit, i.e. 12 months after cessation of exenatide. RESULTS: Compared to the control group of patients, patients previously exposed to exenatide had an advantage of 5.6 points (95% CI, 2.2-9.0; p = 0.002) using blinded video rating of the MDS-UPDRS part 3 motor subscale. There was also a difference of 5.3 points; (95% CI, 9.3-1.4; p = 0.006) between the 2 groups on the Mattis Dementia Rating scale. CONCLUSIONS: While these data must still not be interpreted as evidence of neuroprotection, they nevertheless provide strong encouragement for the further study of this drug as a potential disease modifying agent in Parkinson's disease.

Multifunctional imaging signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations in colorectal cancer.

UNLABELLED: This study explores the potential for multifunctional imaging to provide a signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutations in colorectal cancer. METHODS: This prospective study approved by the institutional review board comprised 33 patients undergoing PET/CT before surgery for proven primary colorectal cancer. Tumor tissue was examined histologically for presence of the KRAS mutations and for expression of hypoxia-inducible factor-1 (HIF-1) and minichromosome maintenance protein 2 (mcm2). The following imaging parameters were derived for each tumor: (18)F-FDG uptake ((18)F-FDG maximum standardized uptake value [SUVmax]), CT texture (expressed as mean of positive pixels [MPP]), and blood flow measured by dynamic contrast-enhanced CT. A recursive decision tree was developed in which the imaging investigations were applied sequentially to identify tumors with KRAS mutations. Monte Carlo analysis provided mean values and 95% confidence intervals for sensitivity, specificity, and accuracy. RESULTS: The final decision tree comprised 4 decision nodes and 5 terminal nodes, 2 of which identified KRAS mutants. The true-positive rate, false-positive rate, and accuracy (95% confidence intervals) of the decision tree were 82.4% (63.9%-93.9%), 0% (0%-10.4%), and 90.1% (79.2%-96.0%), respectively. KRAS mutants with high (18)F-FDG SUVmax and low MPP showed greater frequency of HIF-1 expression (P = 0.032). KRAS mutants with low (18)F-FDG SUV(max), high MPP, and high blood flow expressed mcm2 (P = 0.036). CONCLUSION: Multifunctional imaging with PET/CT and recursive decision-tree analysis to combine measurements of tumor (18)F-FDG uptake, CT texture, and perfusion has the potential to identify imaging signatures for colorectal cancers with KRAS mutations exhibiting hypoxic or proliferative phenotypes.

Qualitative and quantitative comparison of PET/CT and PET/MR imaging in clinical practice.

UNLABELLED: The aim of this study was to prospectively compare whole-body PET/MR imaging and PET/CT, qualitatively and quantitatively, in oncologic patients and assess the confidence and degree of inter- and intraobserver agreement in anatomic lesion localization. METHODS: Fifty patients referred for staging with known cancers underwent PET/CT with low-dose CT for attenuation correction immediately followed by PET/MR imaging with 2-point Dixon attenuation correction. PET/CT scans were obtained according to standard protocols (56 ± 20 min after injection of an average 367 MBq of (18)F-FDG, 150 MBq of (68)Ga-DOTATATE, or 333.8 MBq of (18)F-fluoro-ethyl-choline; 2.5 min/bed position). PET/MR was performed with 5 min/bed position. Three dual-accredited nuclear medicine physicians/radiologists identified the lesions and assigned each to an exact anatomic location. The image quality, alignment, and confidence in anatomic localization of lesions were scored on a scale of 1-3 for PET/CT and PET/MR imaging. Quantitative analysis was performed by comparing the standardized uptake values. Intraclass correlation coefficients and the Wilcoxon signed-rank test were used to assess intra- and interobserver agreement in image quality, alignment, and confidence in lesion localization for the 2 modalities. RESULTS: Two hundred twenty-seven tracer-avid lesions were identified in 50 patients. Of these, 225 were correctly identified on PET/CT and 227 on PET/MR imaging by all 3 observers. The confidence in anatomic localization improved by 5.1% when using PET/MR imaging, compared with PET/CT. The mean percentage interobserver agreement was 96% for PET/CT and 99% for PET/MR imaging, and intraobserver agreement in lesion localization across the 2 modalities was 93%. There was 10% (5/50 patients) improvement in local staging with PET/MR imaging, compared with PET/CT. CONCLUSION: In this first study, we show the effectiveness of whole-body PET/MR imaging in oncology. There is no statistically significant difference between PET/MR imaging and PET/CT in respect of confidence and degree of inter- and intraobserver agreement in anatomic lesion localization. The PET data on both modalities were similar; however, the observed superior soft-tissue resolution of MR imaging in head and neck, pelvis, and colorectal cancers and of CT in lung and mediastinal nodal disease points to future tailored use in these locations.

Areas of normal pulmonary parenchyma on HRCT exhibit increased FDG PET signal in IPF patients.

PURPOSE: Patients with idiopathic pulmonary fibrosis (IPF) show increased PET signal at sites of morphological abnormality on high-resolution computed tomography (HRCT). The purpose of this investigation was to investigate the PET signal at sites of normal-appearing lung on HRCT in IPF. METHODS: Consecutive IPF patients (22 men, 3 women) were prospectively recruited. The patients underwent (18)F-FDG PET/HRCT. The pulmonary imaging findings in the IPF patients were compared to the findings in a control population. Pulmonary uptake of (18)F-FDG (mean SUV) was quantified at sites of morphologically normal parenchyma on HRCT. SUVs were also corrected for tissue fraction (TF). The mean SUV in IPF patients was compared with that in 25 controls (patients with lymphoma in remission or suspected paraneoplastic syndrome with normal PET/CT appearances). RESULTS: The pulmonary SUV (mean ± SD) uncorrected for TF in the controls was 0.48 ± 0.14 and 0.78 ± 0.24 taken from normal lung regions in IPF patients (p < 0.001). The TF-corrected mean SUV in the controls was 2.24 ± 0.29 and 3.24 ± 0.84 in IPF patients (p < 0.001). CONCLUSION: IPF patients have increased pulmonary uptake of (18)F-FDG on PET in areas of lung with a normal morphological appearance on HRCT. This may have implications for determining disease mechanisms and treatment monitoring.

The contribution of medical physics to nuclear medicine: a physician's perspective.

This paper is the second in a series of invited perspectives by four pioneers of nuclear medicine imaging and physics. A medical physicist and a nuclear medicine clinical specialist each take a backward look and a forward look at the contributions of physics to nuclear medicine. Here is a backward look from a nuclear medicine physician's perspective.

Clinical evaluation of reducing acquisition time on single-photon emission computed tomography image quality using proprietary resolution recovery software.

INTRODUCTION: A three-dimensional model-based resolution recovery (RR) reconstruction algorithm that compensates for collimator-detector response, resulting in an improvement in reconstructed spatial resolution and signal-to-noise ratio of single-photon emission computed tomography (SPECT) images, was tested. The software is said to retain image quality even with reduced acquisition time. Clinically, any improvement in patient throughput without loss of quality is to be welcomed. Furthermore, future restrictions in radiotracer supplies may add value to this type of data analysis. AIM: The aims of this study were to assess improvement in image quality using the software and to evaluate the potential of performing reduced time acquisitions for bone and parathyroid SPECT applications. MATERIALS AND METHODS: Data acquisition was performed using the local standard SPECT/CT protocols for 99mTc-hydroxymethylene diphosphonate bone and 99mTc-methoxyisobutylisonitrile parathyroid SPECT imaging. The principal modification applied was the acquisition of an eight-frame gated data set acquired using an ECG simulator with a fixed signal as the trigger. This had the effect of partitioning the data such that the effect of reduced time acquisitions could be assessed without conferring additional scanning time on the patient. The set of summed data sets was then independently reconstructed using the RR software to permit a blinded assessment of the effect of acquired counts upon reconstructed image quality as adjudged by three experienced observers. Data sets reconstructed with the RR software were compared with the local standard processing protocols; filtered back-projection and ordered-subset expectation-maximization. RESULTS: Thirty SPECT studies were assessed (20 bone and 10 parathyroid). The images reconstructed with the RR algorithm showed improved image quality for both full-time and half-time acquisitions over local current processing protocols (P<0.05). CONCLUSION: The RR algorithm improved image quality compared with local processing protocols and has been introduced into routine clinical use. SPECT acquisitions are now acquired at half of the time previously required. The method of binning the data can be applied to any other camera system to evaluate the reduction in acquisition time for similar processes. The potential for dose reduction is also inherent with this approach.

Exenatide and the treatment of patients with Parkinson's disease.

UNLABELLED: BACKGROUND. There is increasing interest in methods to more rapidly and cost-efficiently investigate drugs that are approved for clinical use in the treatment of another condition. Exenatide is a type 2 diabetes treatment that has been shown to have neuroprotective/neurorestorative properties in preclinical models of neurodegeneration. METHODS. As a proof of concept, using a single-blind trial design, we evaluated the progress of 45 patients with moderate Parkinson's disease (PD), randomly assigned to receive subcutaneous exenatide injection for 12 months or to act as controls. Their PD was compared after overnight withdrawal of conventional PD medication using blinded video assessment of the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), together with several nonmotor tests, at baseline, 6 months, and 12 months and after a further 2-month washout period (14 months). RESULTS. Exenatide was well tolerated, although weight loss was common and l-dopa dose failures occurred in a single patient. Single-blinded rating of the exenatide group suggested clinically relevant improvements in PD across motor and cognitive measures compared with the control group. Exenatide-treated patients had a mean improvement at 12 months on the MDS-UPDRS of 2.7 points, compared with mean decline of 2.2 points in control patients (P = 0.037). CONCLUSION. These results demonstrate a potential cost-efficient approach through which preliminary clinical data of possible biological effects are obtainable, prior to undertaking the major investment required for double-blind trials of a potential disease-modifying drug in PD. TRIAL REGISTRATION: Clinicaltrials.gov NCT01174810. FUNDING: Cure Parkinson's Trust.

Tumor heterogeneity and permeability as measured on the CT component of PET/CT predict survival in patients with non-small cell lung cancer.

PURPOSE: We prospectively examined the role of tumor textural heterogeneity on positron emission tomography/computed tomography (PET/CT) in predicting survival compared with other clinical and imaging parameters in patients with non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: The feasibility study consisted of 56 assessed consecutive patients with NSCLC (32 males, 24 females; mean age 67 ± 9.7 years) who underwent combined fluorodeoxyglucose (FDG) PET/CT. The validation study population consisted of 66 prospectively recruited consecutive consenting patients with NSCLC (37 males, 29 females; mean age, 67.5 ± 7.8 years) who successfully underwent combined FDG PET/CT-dynamic contrast-enhanced (DCE) CT. Images were used to derive tumoral PET/CT textural heterogeneity, DCE CT permeability, and FDG uptake (SUVmax). The mean follow-up periods were 22.6 ± 13.3 months and 28.5± 13.2 months for the feasibility and validation studies, respectively. Optimum threshold was determined for clinical stage and each of the above biomarkers (where available) from the feasibility study population. Kaplan-Meier analysis was used to assess the ability of the biomarkers to predict survival in the validation study. Cox regression determined survival factor independence. RESULTS: Univariate analysis revealed that tumor CT-derived heterogeneity (P < 0.001), PET-derived heterogeneity (P = 0.003), CT-derived permeability (P = 0.002), and stage (P < 0.001) were all significant survival predictors. The thresholds used in this study were derived from a previously conducted feasibility study. Tumor SUVmax did not predict survival. Using multivariable analysis, tumor CT textural heterogeneity (P = 0.021), stage (P = 0.001), and permeability (P < 0.001) were independent survival predictors. These predictors were independent of patient treatment. CONCLUSIONS: Tumor stage and CT-derived textural heterogeneity were the best predictors of survival in NSCLC. The use of CT-derived textural heterogeneity should assist the management of many patients with NSCLC.

Comparison of 68Ga-DOTANOC and 68Ga-DOTATATE PET/CT within patients with gastroenteropancreatic neuroendocrine tumors.

UNLABELLED: Somatostatin receptor PET tracers such as [(68)Ga-DOTA,1-Nal(3)]-octreotide ((68)Ga-DOTANOC) and [(68)Ga-DOTA,Tyr(3)]-octreotate ((68)Ga-DOTATATE) have shown promising results in patients with neuroendocrine tumors, with a higher lesion detection rate than is achieved with (18)F-fluorodihydroxyphenyl-l-alanine PET, somatostatin receptor SPECT, CT, or MR imaging. (68)Ga-DOTANOC has high affinity for somatostatin receptor subtypes 2, 3, and 5 (sst2,3,5). It has a wider receptor binding profile than (68)Ga-DOTATATE, which is sst2-selective. The wider receptor binding profile might be advantageous for imaging because neuroendocrine tumors express different subtypes of somatostatin receptors. The goal of this study was to prospectively compare (68)Ga-DOTANOC and (68)Ga-DOTATATE PET/CT in the same patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) and to evaluate the clinical impact of (68)Ga-DOTANOC PET/CT. METHODS: Eighteen patients with biopsy-proven GEP-NETs were evaluated with (68)Ga-DOTANOC and (68)Ga-DOTATATE using a randomized crossover design. Labeling of DOTANOC and DOTATATE with (68)Ga was standardized using a fully automated synthesis device. PET/CT findings were compared with 3-phase CT scans and in some patients with MR imaging, (18)F-FDG PET/CT, and histology. Uptake in organs and tumor lesions was quantified and compared by calculation of maximum standardized uptake values (SUVmax) using volume computer-assisted reading. RESULTS: Histology revealed low-grade GEP-NETs (G1) in 4 patients, intermediate grade (G2) in 7, and high grade (G3) in 7. (68)Ga-DOTANOC and (68)Ga-DOTATATE were false-negative in only 1 of 18 patients. In total, 248 lesions were confirmed by cross-sectional and PET imaging. The lesion-based sensitivity of (68)Ga-DOTANOC PET was 93.5%, compared with 85.5% for (68)Ga-DOTATATE PET (P = 0.005). The better performance of (68)Ga-DOTANOC PET is attributed mainly to the significantly higher detection rate of liver metastases rather than tumor differentiation grade. Multivariate analysis revealed significantly higher SUVmax in G1 tumors than in G3 tumors (P = 0.009). This finding was less pronounced with (68)Ga-DOTANOC (P > 0.001). Altogether, (68)Ga-DOTANOC changed treatment in 3 of 18 patients (17%). CONCLUSION: The sst2,3,5-specific radiotracer (68)Ga-DOTANOC detected significantly more lesions than the sst2-specific radiotracer (68)Ga-DOTATATE in our patients with GEP-NETs. The clinical relevance of this finding has to be proven in larger studies.

Automatic semi-quantification of [123I]FP-CIT SPECT scans in healthy volunteers using BasGan version 2: results from the ENC-DAT database.

PURPOSE: The aim of this study was to assess striatal dopamine transporter (DAT) availability in a large group of normal subjects. METHODS: The study included 122 healthy subjects, aged 18-83 years, recruited in the multicentre 'ENC-DAT' study (promoted by the European Association of Nuclear Medicine). Brain single photon emission computed tomography (SPECT) was acquired by means of dual-head cameras 3 h after [(123)I]FP-CIT administration. Specific to nondisplaceable binding ratios (SBRs) in the basal ganglia were computed using the 'BasGan' software, allowing automatic value extraction with partial volume effect correction. Multicentre camera inhomogeneity was taken into account by calibrating values on basal ganglia phantom data. SBR in each caudate nucleus (C) and putamen (P) were the dependent variables in a repeated measures general linear model analysis; age, gender, handedness and body mass index (BMI) were the independent variables. RESULTS: SBR values in C and P were significantly associated with age (mean rate decrease with age: 0.0306 per year, or 0.57 % of the general mean; p < 0.0001) and gender (women had higher values; p = 0.015), while no significant effect was found for handedness and BMI. A significant interaction was found between age and region (p < 0.0001) as the age-related decline was 0.028 for left C, 0.026 for right C and 0.034 for both P. P/C ratio analysis confirmed that age-related SBR decrease was stronger in P than in C (p < 0.0001). No significant effect was found for season or time of the day when the scan was acquired by analysing the residual of SBR values in C and P, after subtraction of age and gender effects. CONCLUSION: This study confirms the dependency of DAT on ageing and highlights the gender differences in a large sample of healthy subjects, while it does not support the dependency of DAT on BMI, handedness, circadian rhythm or season.

Glucagon-like peptide-1 receptor imaging for the localisation of insulinomas: a prospective multicentre imaging study.

BACKGROUND: Small benign insulinomas are hard to localise, leading to difficulties in planning of surgical interventions. We aimed to prospectively assess the insulinoma detection rate of single-photon emission CT in combination with CT (SPECT/CT) with a glucagon-like peptide-1 receptor avid radiotracer, and compare detection rates with conventional CT/MRI techniques. METHODS: In our prospective imaging study, we enrolled adults aged 25-81 years at centres in Germany, Switzerland, and the UK. Eligible patients had proven clinical and biochemical endogenous hyperinsulinaemic hypoglycaemia and no evidence for metastatic disease on conventional imaging. CT/MRI imaging was done at referring centres according to standard protocols. At three tertiary nuclear medicine centres, we used whole body planar images and SPECT/CT of the abdomen up to 168 h after injection of (111)In-[Lys40(Ahx-DTPA-(111)In)NH2]-exendin-4 ((111)In-DTPA-exendin-4) to identify insulinomas. Consenting patients underwent surgery and imaging findings were confirmed histologically. FINDINGS: Between Oct 1, 2008, and Dec 31, 2011, we recruited 30 patients. All patients underwent (111)In-DTPA-exendin-4 imaging, 25 patients underwent surgery (with histological analysis), and 27 patients were assessed with CT/MRI. (111)In-DTPA-exendin-4 SPECT/CT correctly detected 19 insulinomas and four additional positive lesions (two islet-cell hyperplasia and two uncharacterised lesions) resulting in a positive predictive value of 83% (95% CI 62-94). One true negative (islet-cell hyperplasia) and one false negative (malignant insulinoma) result was identified in separate patients by (111)In-DTPA-exendin-4 SPECT/CT. Seven patients (23%) were referred to surgery on the basis of (111)In-DTPA-exendin-4 imaging alone. For 23 assessable patients, (111)In-DTPA-exendin-4 SPECT/CT had a higher sensitivity (95% [95% CI 74-100]) than did CT/MRI (47% [27-68]; p=0.011). INTERPRETATION: (111)In-DTPA-exendin-4 SPECT/CT could provide a good second-line imaging strategy for patients with negative results on initial imaging with CT/MRI. FUNDING: Oncosuisse, the Swiss National Science Foundation, and UK Department of Health.

Integrated 18F-fluorodeoxyglucose-positron emission tomography/dynamic contrast-enhanced computed tomography to phenotype non-small cell lung carcinoma.

We applied modern molecular and functional imaging to the pretreatment assessment of lung cancer using combined dynamic contrast-enhanced computed tomography (DCE-CT) and (18)F-fluorodeoxyglucose-positron emission tomography ((18)F-FDG-PET) to phenotype tumors. Seventy-four lung cancer patients were prospectively recruited for (18)F-FDG-PET/DCE-CT using PET/64-detector CT. After technical failures, there were 64 patients (35 males, 29 females; mean age [± SD] 67.5 ± 7.9 years). DCE-CT yielded tumor peak enhancement (PE) and standardized perfusion value (SPV). The uptake of (18)F-FDG quantified on PET as the standardized uptake value (SUV(max)) assessed tumor metabolism. The median values for SUV(max) and SPV were used to define four vascular-metabolic phenotypes. There were associations (Spearman rank correlation [rs]) between tumor size and vascular-metabolic parameters: SUV(max) versus size (rs  =  .40, p  =  .001) and SUV/PE versus size (r  =  .43, p < .001). Patients with earlier-stage (I-IIA, n  =  30) disease had mean (± SD) SUV/PE 0.36 ± 0.28 versus 0.56 ± 0.32 in later-stage (stage IIB-IV, n  =  34) disease (p  =  .007). The low metabolism with high vascularity phenotype was significantly more common among adenocarcinomas (p  =  .018), whereas the high metabolism with high vascularity phenotype was more common among squamous cell carcinomas (p  =  .024). Other non-small cell lung carcinoma tumor types demonstrated a high prevalence of the high metabolism with low vascularity phenotype (p  =  .028). We show that tumor subtypes have different vascular-metabolic associations, which can be helpful clinically in managing lung cancer patients to hone targeted therapy.