FDG Positron Emission Tomography Imaging Research Articles

18 F]-Fludarabine Positron Emission Tomography in Chronic Lymphocytic Leukemia Patients: Results of a Phase I Study

Introduction. [18 F]-Fludarabine is a promising novel positron emission tomography (PET) radiotracer for lymphoid malignancies. The rationale supporting its development is the high selectivity of fludarabine uptake within lymphoid cells irrespective of their cycle activity, and the fluorine atom within the drug, which replaced by a [18 F] confers the positron-emitter property. Pre-clinical studies with [18 F]-fludarabine (Dhilly M et al, Mol Imaging Biol 2014,16:118-26; Hovhannisyan N et al, EJNMMI Res 2015,5:23) showed a marked tumor uptake in lymphoma-bearing mice. The aim of this study was to describe anatomical sites with abnormal [18 F]-fludarabine uptake in patients with B-cell chronic lymphocytic leukemia (B-CLL), in whom [18 F]-FDG PET imaging appears to be less informative than in other lymphoid malignancies. This study was designed as a clinical proof of concept.Methods. [18 F]-Fludarabine was produced according to a method already described (Guillouet S et al, Mol Imaging Biol 2014,16:28-35). [18 F]-Fludarabine PET/CT (Discovery RX VCT 64, GE Healthcare) was performed in 5 patients (51-70 years old) with a diagnosis of B-CLL (according to current recommendations), without suspicion of Richter's syndrome. Successive partial body scans (skull vertex to mid-thigh) were acquired for 250 min after intravenous injection of [18 F]-fludarabine with an activity of 4MBq/kg. PET images were analyzed by drawing volumes of interest (VOI) over the uptake sites on a late scan and projected onto all co-registered scans of the same subject. The intensity of tracer uptake was evaluated with the maximum standardized uptake value (SUVmax). The images of [18 F]-fludarabine PET/CT were visually compared with conventional modalities (high-resolution CT) and [18 F]-FDG PET in one patient.Results. No adverse event was recorded during and after the procedure. In the 5 patients studied, the uptake of [18 F]-fludarabine coincides with sites expected to be involved following conventional clinical and CT scan staging (i.e. lymph nodes, spleen, tonsils). Additionally, [18 F]-fludarabine PET/CT displayed a significant uptake in hematopoietic bone marrow, and unexpected uptake in the medulla of some bones (femur, humerus, sphenoid, calvarium), and in Peyer's patches. SUVmax were significantly greater in involved sites in comparison with normal tissues or organs (Figure 1). Within the involved sites, [18 F]-fludarabine demonstrated a wide range of uptake which would indicate heterogeneity and differing micro-environments. For instance, the most active sites of the case illustrated in Figure 1 (scan period 30-50 min) are lymph nodes (SUVmax 7.4), spleen (SUVmax 6.3) and bone marrow (SUVmax 3.8) with aortic uptake (SUVmax 1.5) as background level.Conclusion. These preliminary results showed a clear specificity of this novel radiotracer for lymphoid tissues. [18 F]-Fludarabine PET/CT appears to be a promising tool for the diagnosis and follow-up of B-CLL. These scans indicate variable activity within proliferation sites, information otherwise not accessible by current non-invasive procedures. Further studies for a more accurate comparison with [18 F]-FDG PET, evaluation of response during and after treatment and correlation with B-CLL prognostic criteria are underway. [Display omitted] [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Prediction of standard-dose brain PET image by using MRI and low-dose brain [18F]FDG PET images.

Positron emission tomography (PET) is a nuclear medical imaging technology that produces 3D images reflecting tissue metabolic activity in human body. PET has been widely used in various clinical applications, such as in diagnosis of brain disorders. High-quality PET images play an essential role in diagnosing brain diseases/disorders. In practice, in order to obtain high-quality PET images, a standard-dose radionuclide (tracer) needs to be used and injected into a living body. As a result, it will inevitably increase the patient's exposure to radiation. One solution to solve this problem is predicting standard-dose PET images using low-dose PET images. As yet, no previous studies with this approach have been reported. Accordingly, in this paper, the authors propose a regression forest based framework for predicting a standard-dose brain [(18)F]FDG PET image by using a low-dose brain [(18)F]FDG PET image and its corresponding magnetic resonance imaging (MRI) image. The authors employ a regression forest for predicting the standard-dose brain [(18)F]FDG PET image by low-dose brain [(18)F]FDG PET and MRI images. Specifically, the proposed method consists of two main steps. First, based on the segmented brain tissues (i.e., cerebrospinal fluid, gray matter, and white matter) in the MRI image, the authors extract features for each patch in the brain image from both low-dose PET and MRI images to build tissue-specific models that can be used to initially predict standard-dose brain [(18)F]FDG PET images. Second, an iterative refinement strategy, via estimating the predicted image difference, is used to further improve the prediction accuracy. The authors evaluated their algorithm on a brain dataset, consisting of 11 subjects with MRI, low-dose PET, and standard-dose PET images, using leave-one-out cross-validations. The proposed algorithm gives promising results with well-estimated standard-dose brain [(18)F]FDG PET image and substantially enhanced image quality of low-dose brain [(18)F]FDG PET image. In this paper, the authors propose a framework to generate standard-dose brain [(18)F]FDG PET image using low-dose brain [(18)F]FDG PET and MRI images. Both the visual and quantitative results indicate that the standard-dose brain [(18)F]FDG PET can be well-predicted using MRI and low-dose brain [(18)F]FDG PET.

Monitoring therapeutic efficacy of sunitinib using [(18)F]FDG and [(18)F]FMISO PET in an immunocompetent model of luminal B (HER2-positive)-type mammary carcinoma.

BackgroundClinical studies implying the sunitinib multi-kinase inhibitor have led to disappointing results for breast cancer care but mostly focused on HER2-negative subtypes. Preclinical researches involving this drug mostly concern Triple Negative Breast Cancer (TNBC) murine models. Here, we explored the therapeutic efficacy of sunitinib on a PyMT-derived transplanted model classified as luminal B (HER2-positive) and monitored the response to treatment using both in vivo and ex vivo approaches.MethodsTumour-induced animals were treated for 9 (n = 7) or 14 (n = 8) days with sunitinib at 40 mg/kg or with vehicle only. Response to therapy was assessed in vivo by monitoring glucose tumour metabolism and hypoxia using 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) and [18F]fluoromisonidazole ([18F]FMISO) Positron Emission Tomography (PET). After primary tumour excision, ex vivo digital microscopy was performed on treated and control samples to estimate vascular density (CD31), apoptosis (Tunel), proliferation (Ki-67), Tumour-Associated Macrophage (TAM) infiltration (F4/80), metabolism (GLUT1) and cellular response to hypoxia (HIF1 alpha). The drug impact on the metastasis rate was evaluated by monitoring the PyMT gene expression in the lungs of the treated and control groups.ResultsConcomitant with sunitinib-induced tumour size regression, [18F]FDG PET imaging showed a stable glycolysis-related metabolism inside tumours undergoing treatment compared to an increased metabolism in untreated tumours, resulting at treatment end in 1.5 less [18F]FDG uptake in treated (n = 4) vs control (n = 3) tumours (p < 0.05). With this small sample, [18F]FMISO PET showed a non-significant decrease of hypoxia in treated vs control tumours. The drug triggered a 4.9 fold vascular volume regression (p < 0.05), as well as a 17.7 fold induction of tumour cell apoptosis (p < 0.001). The hypoxia induced factor 1 alpha (HIF1 alpha) expression was twice lower in the treated group than in the control group (p < 0.05). Moreover, the occurrence of lung metastases was not reduced by the drug.Conclusions[18F]FDG and [18F]FMISO PET were relevant approaches to study the response to sunitinib in this luminal B (HER2-positive) model. The sunitinib-induced vascular network shrinkage did not significantly increase tumour hypoxia, suggesting that tumour regression was mainly due to the pro-apoptotic properties of the drug. Sunitinib did not inhibit the metastatic process in this PyMT transplanted model.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1540-2) contains supplementary material, which is available to authorized users.

Improving (18)F-Fluoro-D-Glucose-Positron Emission Tomography/Computed Tomography Imaging in Alzheimer's Disease Studies.

The goal was to improve Alzheimer's 2-deoxy-2-18F-fluoro-D-glucose (18F FDG)-positron emission tomography (PET)/computed tomography (CT) imaging through application of a novel, hybrid Fourier-wavelet windowed Fourier transform (WFT) restoration technique, in order to provide earlier and more accurate clinical results. General Electric Medical Systems downward-looking sonar PET/CT 16 slice system was used to acquire studies. Patient data were acquired according the Alzheimer's disease Neuroimaging Initiative (ADNI) protocol. Here, we implemented Fourier-wavelet regularized restoration, with a Butterworth low-pass filter, order n = 6 and a cut-off frequency f = 0.35 cycles/pixel and wavelet (Daubechies, order 2) noise suppression. The original (PET-O) and restored (PET-R) ADNI subject PET images were compared using the Alzheimer's discrimination analysis by dedicated software. Forty-two PET/CT scans were used in the study. They were performed on eleven ADNI subjects at intervals of approximately 6 months. The final clinical diagnosis was used as a gold standard. For three subjects, the final clinical diagnosis was mild cognitive impairment and those 13 PET/CT studies were not included in the final comparison, as the result was considered as inconclusive. Using the reminding 29 PET/CT studies (23 AD and 6 normal), the sensitivity and specificity of the PET-O and PET-R were calculated. The sensitivity was 0.65 and 0.96 for PET-O and PET-R, respectively, and the specificity was 0.67 and 0.50 for PET-O and PET-R. The accuracy was 0.66 and 0.86 for PET-O and PET-R, respectively. The results of the study demonstrated that the accuracy of three-dimensional brain F-18 FDG PET images was significantly improved by Fourier-wavelet restoration filtering.

18F-FDG PET/MRI for therapy response assessment in sarcoma: comparison of PET and MR imaging results

Background18F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) has proven to be of substantial benefit in imaging of sarcoma patients. We therefore investigated the feasibility and benefit of combined PET/magnetic resonance imaging (MRI). MethodsTwelve patients with sarcoma who underwent FDG PET/MRI for staging and response assessment after chemotherapy were included. ResultsBased on contrast-enhanced MRI and application of Choi criteria, therapy response was classified as stable disease in 6/12 patients (50%) and as partial remission in 6/12 patients (50%). ConclusionIn sarcoma patients, response assessment using Choi criteria based on contrast-enhanced MRI in comparison to FDG PET imaging only demonstrates slight correlation.

Roles of facilitative glucose transporter GLUT1 in [18F]FDG positron emission tomography (PET) imaging of human diseases

The facilitative glucose transport protein GLUT1 has important roles in positron emission tomography (PET) imaging of human diseases. GLUT1 has widespread expression and catalyses the energyindependent facilitated diffusion of glucose down its concentration gradient across red blood cell membranes, blood-brain and blood-tissue barriers and membranes of some oragnelles. Import is usually the prevailing direction of transport for providing metabolic fuel, especially in proliferating cells. PET imaging using 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) measures the uptake of [ 18 F]FDG into cells and tissues as a marker of glucose transport and glycolytic activity. Diseases can alter glycolytic activity in localised regions of tissues or organs, which can be visualised using [ 18 F]FDG PET. Expression and/or activity levels of GLUT1 contribute to the pattern and intensity of [ 18 F]FDG. [ 18 F]FDG PET imaging is used in diagnosing and monitoring a range of human diseases and in analysing their response to treatments. Proliferating cancer cells display overexpression of GLUT1 and a vastly higher rate of glycolysis for satisfying their increased nutrient demands. Tumours therefore have significantly enhanced [ 18 F]FDG uptake compared with normal cells, so [ 18 F]FDG PET is routinely used in diagnosing and monitoring cancers. [ 18 F]FDG PET imaging of the brain allows identification of distinct patterns of hypometabolism and/or hypermetabolism associated with neurological disorders including Alzheimer’s disease, Parkinson’s disease, epilespsy,

Abstract 2058: Molecular imaging of glutaminolysis as a tool for evaluating therapeutic response in preclinical models of colorectal cancer

Abstract The metabolic repertoire of cancer cells diverge significantly from that of normal cells. Energy production in cancer cells tends to depend on aerobic glycolysis, a feature that is routinely monitored by positron emission tomography (PET) imaging using 2-[18F]fluoro-2-deoxy-D-glucose ([18F]FDG). In addition to predilection for glycolysis, cancer cells may possess other unique metabolic characteristics, such as increased consumption of glutamine. As with glucose, glutamine also serves as a key carbon source for ATP production and biosynthesis. Given this, quantitative measures of glutaminolysis may reflect critical processes in oncology. Accordingly, PET agents targeting glutamine uptake, such as 4-[18F]fluoro-glutamine ([18F]4F-GLN), have been reported and used in preclinical models of cancer. The goal of this study was to elucidate the feasibility of using [18F]4F-GLN PET to predict response to targeted therapy within the context of colorectal cancer (CRC). Initially we validated expression of SLC1A5, the primary plasma membrane transporter of glutamine, in tumor and normal colon specimens for 58 patients with primary and advanced CRC. We found that SLC1A5 expression was elevated in over 80%of primary tumor specimens but did not correlate with grade or gender. Furthermore, elevated SLC1A5 expression correlated strongly with elevated Ki67, a molecular marker of proliferation. Given this, we evaluated [18F]4F-GLN PET in preclinical models of V600EBRAF-expressing CRC as a means of detecting anti-proliferation responses to targeted therapeutics. Simulating a clinical study within the context of the Vanderbilt GI SPORE, the regimen included an inhibitor of mutant BRAF, a PI3K/mTOR inhibitor, and a combination there of. Strikingly, [18F]4F-GLN PET was found to correlate more closely to markers of anti-proliferative responses in vivo than analogously performed [18F]FDG PET imaging studies. We believe that these findings not only provide a greater understanding of the role that glutaminolysis plays in CRC but also illuminate the potential impact that glutaminolysis derived PET could have towards guiding drug development clinical trials as an imaging metric of early therapeutic response detection. Citation Format: Matthew R. Hight, Michael L. Schulte, Samir Saleh, Gregory D. Ayers, Frank L. Revetta, M. Kay Washington, Robert J. Coffey, H. Charles Manning. Molecular imaging of glutaminolysis as a tool for evaluating therapeutic response in preclinical models of colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2058. doi:10.1158/1538-7445.AM2014-2058

In vivo [¹⁸F] FDG PET imaging reveals that p-chloroamphetamine neurotoxicity is associated with long-term cortical and hippocampal hypometabolism.

p-Chloroamphetamine (PCA) is a neurotoxin that selectively degenerates the serotonin (5-HT) axon terminals. In order to study the brain metabolic consequences induced by serotonergic denervation, a single dose of PCA (2.5 or 10 mg/kg i.p.) was administered to male adult rats. In vivo regional brain metabolism was evaluated 3 and 21 days after PCA (2.5 or 10 mg/kg; i.p.) injection by 2-deoxy-2-[(18)F] fluoro-D-glucose ([(18)F] FDG) positron emission tomography (PET). At day 22, the following markers of neurotoxicity were determined: (a) 5-HT axon terminal lesion by 5-HT transporter (SERT) autoradiography, (b) reactive gliosis by glial fibrillary acidic protein immunohistochemistry, and (c) eventual neurodegeneration by DAPI/Fluoro-Jade C labeling. An average of 20 % reduction of [(18)F] FDG uptake in most brain areas was observed at day 21 under 10 mg/kg PCA treatment. Instead, 2.5 mg/kg PCA only reduced metabolic activity in neocortex. Likewise, the high dose of PCA exerted a strong decrease (>30 %) in SERT density in several 5-HT innervated regions, but no effect was found in midbrain raphe nuclei, the main source of serotonergic neurons. Although PCA induced astroglial activation both in hippocampus and cortex in response to axotomy, no signs of neuronal death in these areas were detected. Overall, [(18)F] FDG PET revealed that the reduction of the brain metabolic activity induced by PCA is related to 5-HT axon terminal lesion, with no apparent affectation of neuronal viability.

Visualization of angiogenesis during cancer development in the polyoma middle T breast cancer model: molecular imaging with (R)-[11C]PAQ

BackgroundVascular endothelial growth factor receptor 2 (VEGFR2) is a crucial mediator of tumour angiogenesis. High expression levels of the receptor have been correlated to poor prognosis in cancer patients. Reliable imaging biomarkers for stratifying patients for anti-angiogenic therapy could therefore be valuable for increasing treatment success rates. The aim of this study was to investigate the pharmacokinetics and angiogenesis imaging abilities of the VEGFR2-targeting positron emission tomography (PET) tracer (R)-[11C]PAQ.Methods(R)-[11C]PAQ was evaluated in the mouse mammary tumour virus-polyoma middle T (MMTV-PyMT) model of metastatic breast cancer. Mice at different stages of disease progression were imaged with (R)-[11C]PAQ PET, and results were compared to those obtained with [18 F]FDG PET and magnetic resonance imaging. (R)-[11C]PAQ uptake levels were also compared to ex vivo immunofluorescence analysis of tumour- and angiogenesis-specific biomarkers. Additional pharmacokinetic studies were performed in rat and mouse.ResultsA heterogeneous uptake of (R)-[11C]PAQ was observed in the tumorous mammary glands. Ex vivo analysis confirmed the co-localization of areas with high radioactivity uptake and areas with elevated levels of VEGFR2. In some animals, a high focal uptake was observed in the lungs. The lung uptake correlated to metastatic and angiogenic activity, but not to uptake of [18 F]FDG PET. The pharmacokinetic studies revealed a limited metabolism and excretion during the 1-h scan and a distribution of radioactivity mainly to the liver, kidneys and lungs. In rat, a high uptake was additionally observed in adrenal and parathyroid glands.ConclusionThe results indicate that (R)-[11C]PAQ is a promising imaging biomarker for visualization of angiogenesis, based on VEGFR2 expression, in primary tumours and during metastasis development.

Adrenergic pathway activation enhances brown adipose tissue metabolism: A [18F]FDG PET/CT study in mice

Pharmacologic approaches to study brown adipocyte activation in vivo with a potential of being translational to humans are desired. The aim of this study was to examine pre- and postsynaptic targeting of adrenergic system for enhancing brown adipose tissue (BAT) metabolism quantifiable by [(18)F]fluoro-2-deoxyglucose ([(18)F]FDG) positron emission tomography (PET)/computed tomography (CT) in mice. A β₃-adrenoreceptor selective agonist (CL 316243), an adenylyl cyclase enzyme activator (forskolin) and a potent blocker of presynaptic norepinephrine transporter (atomoxetine), were injected through the tail vein of Swiss Webster mice 30 minutes before intravenous (iv) administration of [(18)F]FDG. The mice were placed on the PET/CT bed for 30 min PET acquisition followed by 10 min CT acquisition for attenuation correction and anatomical delineation of PET images. Activated interscapular (IBAT), cervical, periaortic and intercostal BAT were observed in 3-dimentional analysis of [(18)F]FDG PET images. CL 316243 increased the total [(18)F]FDG standard uptake value (SUV) of IBAT 5-fold greater compared to that in placebo-treated mice. It also increased the [(18)F]FDG SUV of white adipose tissue (2.4-fold), and muscle (2.7-fold), as compared to the control. There was no significant difference in heart, brain, spleen and liver uptakes between groups. Forskolin increased [(18)F]FDG SUV of IBAT 1.9-fold greater than that in placebo-treated mice. It also increased the [(18)F]FDG SUV of white adipose tissue (2.2-fold) and heart (5.4-fold) compared to control. There was no significant difference in muscle, brain, spleen, and liver uptakes between groups. Atomoxetine increased [(18)F]FDG SUV of IBAT 1.7-fold greater than that in placebo-treated mice. There were no significant differences in all other organs compared to placebo-treated mice except liver (1.6 fold increase). A positive correlation between SUV levels of IBAT and CT Hounsfield unit (HU) (R(2)=0.55, p<0.001) and between CT HU levels of IBAT and liver (R(2)=0.69, p<0.006) was observed. The three pharmacologic approaches reported here enhanced BAT metabolism by targeting different sites in adrenergic system as measured by [(18)F]FDG PET/CT.

THU0085 Effect of CSF-1R Kinase Inhibitor on FDG PET, MMP Optical, and Microct Imaging in a Rat SCW Model of Rheumatoid Arthritis: Use of Functional and Structural Imaging as Translation Tools

BackgroundTissue macrophage recruitment and osteoclastogenesis is dependent on the activation of colony stimulating factor-1 (CSF-1) receptor (R). To target macrophages and block osteoclastogenesis a JNJ compound was identified as a...

Abstract 2661: C11 Acetate and 18F FDG PET/CT imaging of MDR2-/- mouse model of hepatocellular carcinoma.

Abstract Our previous research reveals a link between the enzyme autotaxin (ATX) and its product lysophosphatidic acid (LPA) in hepatocellular carcinoma (HCC). We have shown a shift in ATX levels and LPA variant biosynthesis associated with HCC in patients that was corrected by liver transplantation. Moreover we have demonstrated a reduction in hepatic tumor burden in the MDR2-/- mouse model of HCC by treatment with commercial ATX inhibitors. The purpose of this study was to establish the relevance of FDG PET versus 11C acetate imaging to monitor response to ATX inhibition in the in-vivo MDR2 /- mouse model of HCC whereby we would be able to test the impact of novel inhibitors on both the initiation and progression of HCC. Methods: Dynamic high-resolution Positron Emission Tomography (PET) images of 12 month MDR-/- mice and FVB controls were acquired using 18F-FDG or 11C-Acetate (N=3 per group). At the end of the PET imaging session whole body CT images were acquired. Image segmentation for discrete volumes of interests (VOI) was manually constructed from parametric images for the liver for 18F-FDG images while for 11C-Acetate VOIs were submitted to kinetic modeling, using a 3-compartment, 4-parameter model. Results. MDR2-/- mice had significant hepatic tumors at 12 month (7.9±1.8mm) whereas no tumors were observed in FVB controls. MDR2-/- mice had significantly higher hepatic 11C-Acetate uptake and metabolic rates when compared to FVB controls (0.6±0.04 vs 0.49±0.02ml/g/min P=0.038). In contrast there was no significant difference in 18F-FDG metabolism or uptake in the livers of MDR2-/- mice when compared to wild type FVB controls (1.1±0.23 v 1.32±0.2 and 3.61±0.97 vs. 4.3±0.6SUV respectively p=ns). Conclusion: The biology of HCC formation in MDR2-/- is better suited to 11C acetate PET/CT imaging than 18F FDG. 11C acetate is the most effective imaging method available to test response to treatment in an in-vivo model of HCC. Citation Format: Nicholas J. Skill, Paul R. Territo, Amanda A. Riley, Brian P. McCarthy, Mary A. Maluccio. C11 Acetate and 18F FDG PET/CT imaging of MDR2-/- mouse model of hepatocellular carcinoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2661. doi:10.1158/1538-7445.AM2013-2661 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.

Metabolic brain network in the Chinese patients with Parkinson's disease based on 18F-FDG PET imaging

The objective of this study was to validate Parkinson's disease-related pattern (PDRP) as a measure of network biomarker of Parkinson's disease (PD) in Chinese population by using 18F-fluorodeoxyglucose (FDG) and Positron Emission Tomography (PET). Resting-state brain FDG PET imaging was performed in a cohort of 33 PD patients and 33 age/gender-matched healthy controls to identify a PDRP. PDRP expression was then computed in a new cohort of 30 PD patients and 30 healthy controls using a voxel-based network quantification algorithm. Differences in PDRP expression were compared across groups and correlations with severities of PD were investigated. As a result, we identified a PDRP characterized by relative increases in pallidothalamic, pontine, and cerebellar metabolism, associated with concurrent metabolic decreases in the premotor and posterior parietal areas. PDRP expression in each of the two PD groups was significantly elevated relative to that of the healthy controls (P < 0.001). Receiver operating characteristic (ROC) analysis revealed that the PDRP-based discrimination for PD patients and controls had high sensitivity and specificity (both = 93.9%) in the derivation cohort, which declined slightly in the validation cohort (both = 90.0%) at the same diagnostic threshold. Moreover, PDRP scores correlated positively with Hoehn and Yahr scores (r ≥ 0.590, P ≤ 0.001) and Unified Parkinson's Disease Rating Scale motor scores (r ≥ 0.646, P < 0.001) in both patient groups. In conclusion, PDRP is highly reproducible in Chinese cohorts based on FDG PET imaging. Network activity of PDRP can differentiate PD patients from healthy controls and correlates with the severities of the disease.

Abstract 2369: Correlating circulating tumor cells with 18F-FDG positron emission tomography (PET) uptake in patients with treatment naïve non-small cell lung cancer: A pilot study

Abstract BACKGROUND: Circulating tumor cells (CTCs) represent disease derived cells identified in the blood of cancer patients with prognostic implications. 18F-2-fluoro-2-deoxyglucose (FDG) PET tumor uptake in non-small cell lung cancer (NSCLC) may be associated with poor prognosis despite therapy since the tracer accumulates in increasing amounts in more aggressive cancers. We therefore set out to investigate whether CTCs correlate with FDG uptake. METHODS: For this multi-center, prospective, observational study patients were consented and underwent phlebotomy into a cell preservative blood collection tube. Samples were shipped at ambient temperature and processed within 36 hours. CTC detection was defined by immunofluorescence (CK, DAPI, CD45) followed by automated morphometric analysis that was validated manually. Patients who underwent surgery or had medical treatment prior to imaging were excluded and only those with biopsy proven NSCLC who had PET images acquired within 4 weeks of CTC sample procurement were eligible. Semi-quantitative values (maximum standardized uptake value [SUVmax]) were extracted from images using a region of interest drawn over the tumor by the interpreting physician. Correlations were calculated by either a Pearson or Spearman-rank test depending on the distribution of the underlying variable. RESULTS: Twenty-six patients with treatment naïve NSCLC underwent phlebotomy for CTCs and had FDG PET imaging done at four medical centers during the pilot phase of this study. Five patients were excluded for further analysis due to pending results or more than 4 weeks from PET imaging to CTC draw. The average age for this cohort was 67 (± 11) years, 13 of 21 patients were male (62%) and 71% were stage I or II NSCLC. Mean tumor size was 3.0 cm (range 1.5-7.5 cm), median SUVmax was 7.4 (IQR 4.4-16.1) and two-thirds of patients had adenocarcinoma. At least one CTC per ml was detected in 81% of patients (17/21), and the median CTC count was 27 per ml (IQR 2.4-59.0) across all samples and histologic types. CTCs appeared to correlate more with tumor size (r=0.42) than with glucose metabolism as measured by SUVmax (r=0.22). CONCLUSION: We have established a multi-center workflow to expeditiously study tumor glucose metabolism using imaging and in-vitro diagnostics. Preliminary data show good sensitivity for a combined immunofluorescent and cytometric CTC detection approach in early-stage disease. CTC count may not correlate well with tumor glucose metabolism in NSCLC but further study is required. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2369. doi:1538-7445.AM2012-2369

Anomalous PiB enhancement in the Superior Sagittal and Transverse Venous Sinuses

Pittsburgh compound-B (PiB), an amyloid-binding positron emission tomography (PET) tracer, is widely used for imaging amyloid-β in those with and at risk for Alzheimer disease. Here, we report on an otherwise normal 68-year-old female with abnormally high and very focal PiB retention. Coregistered T1-weighted magnetic resonance imaging and dynamic 2-fluoro-2-deoxy-D-glucose (FDG) images confirmed that the focal PiB enhancement was in the superior sagittal and transverse sinuses, outside of the adjacent cortex. Flow through the venous vasculature was normal as assessed by dynamic FDG PET imaging. These features supported the conclusion that PiB retention was not simply due to a hemodynamic abnormality, but may have represented PiB binding to fibrillar deposits of a β-sheet protein (ie, amyloid), whose nature is currently unclear.

Application of Metabolic PET Imaging in Radiation Oncology

Positron emission tomography (PET) is a noninvasive imaging technique that provides functional or metabolic assessment of normal tissue or disease conditions and is playing an increasing role in cancer radiotherapy planning. (18)F-Fluorodeoxyglucose PET imaging (FDG-PET) is widely used in the clinic for tumor imaging due to increased glucose metabolism in most types of tumors; its role in radiotherapy management of various cancers is reviewed. In addition, other metabolic PET imaging agents at various stages of preclinical and clinical development are reviewed. These agents include radiolabeled amino acids such as methionine for detecting increased protein synthesis, radiolabeled choline for detecting increased membrane lipid synthesis, and radiolabeled acetate for detecting increased cytoplasmic lipid synthesis. The amino acid analogs choline and acetate are often more specific to tumor cells than FDG, so they may play an important role in differentiating cancers from benign conditions and in the diagnosis of cancers with either low FDG uptake or high background FDG uptake. PET imaging with FDG and other metabolic PET imaging agents is playing an increasing role in complementary radiotherapy planning.

Comparison Between Endoscopic Macroscopic Classification and F-18 FDG PET Findings in Gastric Mucosa–Associated Lymphoid Tissue Lymphoma Patients

The aim of this study was to compare endoscopic macroscopic classification with fluorine-18 fluorodeoxyglucose (F-18 FDG) uptake in gastric mucosa-associated lymphoid tissue (MALT) lymphoma and to investigate the usefulness of F-18 FDG positron emission tomography (PET) for diagnosing gastric MALT lymphoma. Sixteen patients with gastric MALT lymphoma who underwent F-18 FDG PET and gastrointestinal imaging modalities were included in this study. Sixteen healthy asymptomatic participants undergoing both F-18 FDG PET and endoscopy for cancer screening were in the control group. We investigated the difference of F-18 FDG uptake between the gastric MALT lymphoma and the control group and compared the uptake pattern in gastric MALT lymphoma with our macroscopic classification. The endoscopic findings of 16 gastric MALT lymphoma patients were classified macroscopically as chronic gastritis-like tumors (n = 6), depressed tumors (n = 5), and protruding tumors (n = 5). Abnormal gastric F-18 FDG uptake was observed in 63% of tumors in the gastric MALT lymphoma group and 50% of cases in the control group. The median maximum standardized uptake values for gastric MALT lymphoma patients and control group were 4.0 and 2.6, respectively, the difference of which was statistically significant (P = 0.003). F-18 FDG uptake results were positive for all protruding tumors but only 50% for chronic gastritis-like tumors and 40% for depressed-type tumors. F-18 FDG PET may be a useful method for evaluating protrusion-type gastric MALT lymphoma. When strong focal or diffuse F-18 FDG uptake is detected in the stomach, endoscopic biopsy should be performed, even if the endoscopic finding is chronic gastritis.

Result of FDG PET Imaging After Chemotherapy +/− Immunotherapy Is a Significant and Independent Prognostic Indicator of Outcome for Patients with Follicular Lymphoma: Survey From a Single Institution

Abstract 2674 AimFDG positron emission tomography (PET) is the mainstay of response evaluation in some lymphoma subgroups such as DLBCL or HL according to Cheson criteria 2007. Due to its indolent behaviour, PET restaging has been poorly explored in Follicular Lymphoma (FL) Methods:The analysis was retrospectively conducted in pts with FL who underwent whole-body 18F-FDG-PET as part of response evaluation at the end of first line or savage treatment program at our institution from August 2001 to June 2010. Results:Seventy five patients were identified. Main clinical characteristics: median age 58 (range 26– 78); male 37 pts; B symptoms 6 pts; bulky disease 5 pts; stage IV 42 pts; bone marrow involvement 32 pts. Fifty-five pts were evaluated after first line treatment program, while 20 pts after salvage therapy program. Main chemotherapy regimen: CHOP or CHOP-like 38, CVP 11, polichemotherapy containing high-dose cytosine-arabinoside 11, fludarabine containing regimens 4. Furthermore, 19 pts underwent autologous peripheral stem-cell transplantation after either first line or salvage therapy. Eleven pts also received consolidation radiotherapy. Forty-two pts received Rituximab during chemotherapy. At the end of treatment, 54 pts reached complete remission as confirmed by PET. With a median follow-up of 53 months, a significantly lower actuarial 4yr PFS was observed in post-treatment PET+ versus. PET- patients: 35.1% vs. 74.8% (log rank p<0.01). Among all other prognostic factors analyzed (B-symptoms, bulky disease, chemotherapy regimens, chemotherapy vs chemoimmunotherapy, first line therapy vs salvage chemotherapy), only stage IV showed a correlation with PFS.In a multivariate Cox model including all patients, post-treatment PET+ (HR 2.20; C.I. 95%: 1.02–4.76 p<0.04) and Stage IV (HR 3.08; C.I. 95%: 1.23–7.73 p<0.01) were unfavorable predictors for PFS. Conclusion:This retrospective study demonstrates that post-treatment negative PET is a powerful predictor for PFS. Patients who are PET- can expect a prolonged PFS either in first line or successive lines of treatment. Future clinical trials are needed to evaluate a PET oriented approach focused on improving outcomes according to PET response.PET-PET+N°5421PFS %74.835.1 Disclosures:No relevant conflicts of interest to declare.

FDG–PET imaging, EEG and sleep phenotypes as translational biomarkers for research in Alzheimer's disease

The lack of reliable translational procedures applicable to both patients and experimental models are a major obstacle for the advancement of basic research as well as for the development of therapeutics. This is particularly relevant to neurodegenerative disorders such as AD (Alzheimer's disease), where the predictive validity of animal models and procedures applied preclinically have met with little success. Two approaches available for human diagnostics are currently experiencing major advancements in preclinical research: in vivo imaging using MRI (magnetic resonance imaging) or PET (positron-emission tomography) and recordings of brain electrical activity via surface EEG (electroencephalogram). The present paper reviews the results obtained so far in rodent AD models, and summarizes advantages and disadvantages of such procedures.

Evolving role of FDG PET imaging in assessing joint disorders: a systematic review

Assessing joint disorders has been a relatively recent and evolving application of 18F-2-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography (PET) imaging. FDG is taken up by inflammatory cells, particularly when they are active as part of an ongoing inflammatory process. Hence FDG PET has been employed to assess a wide array of arthritic disorders. FDG PET imaging has been investigated in various joint diseases for diagnostic purposes, treatment monitoring, and as a prognostic indicator as in other disorders. In some of the diseases the ancillary findings in FDG PET have provided important clues about the underlying pathophysiology and pathogenesis processes. While substantial promise has been demonstrated in a number of studies, it is clear that the potential utility of PET in this clinical realm far outweighs that which has been established to date.