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1.  PET Regional Cerebral Blood Flow Change During Working and Declarative Memory: Relationship With Task Performance 
Neuropsychology  1997;11(2):222-231.
Functional and anatomical relationships between working and declarative memory were investigated by contrasting regional cerebral blood flow (rCBF) change during standard working (Wisconsin Card Sorting Test, WCST) and declarative memory (Paired Associate Recognition Test, PART) tasks using identical stimulus–response modalities. The tasks and a resting baseline were administered to 30 participants (16 men, 14 women) during successive 10-min positron emission tomography 15O-water measures of rCBF. For both tasks, rCBF increased over baseline in inferior frontal and occipitotemporal regions, with more consistent dorsolateral prefrontal activation for WCST than PART. Additional orbitofrontal increases and dorsomedial decreases were seen for the PART. Activation patterns diverged when performance was considered. For the WCST, high performers activated dorsolateral and inferior frontal regions, whereas top PART performers activated only the occipitotemporal region. These results suggest operation of a frontotemporal network subserving both types of memory function that becomes more focal as performance increases.
PMCID: PMC4332579  PMID: 9110329
2.  Effect of Schizophrenia on Frontotemporal Activity During Word Encoding and Recognition: A PET Cerebral Blood Flow Study 
The American journal of psychiatry  2001;158(7):1114-1125.
Neuropsychological studies have shown that deficits in verbal episodic memory in schizophrenia occur primarily during encoding and retrieval stages of information processing. The current study used positron emission tomography to examine the effect of schizophrenia on change in cerebral blood flow (CBF) during these memory stages.
CBF was measured in 23 healthy comparison subjects and 23 patients with schizophrenia during four conditions: resting baseline, motor baseline, word encoding, and word recognition. The motor baseline was used as a reference that was subtracted from encoding and recognition conditions by using statistical parametric mapping.
Patients’ performance was similar to that of healthy comparison subjects. During word encoding, patients showed reduced activation of left prefrontal and superior temporal regions. Reduced left prefrontal activation in patients was also seen during word recognition, and additional differences were found in the left anterior cingulate, left mesial temporal lobe, and right thalamus. Although patients’ performance was similar to that of healthy comparison subjects, left inferior prefrontal activation was associated with better performance only in the comparison subjects.
Left frontotemporal activation during episodic encoding and retrieval, which is associated with better recognition in healthy people, is disrupted in schizophrenia despite relatively intact recognition performance and right prefrontal function. This may reflect impaired strategic use of semantic information to organize encoding and facilitate retrieval.
PMCID: PMC4332582  PMID: 11431234
3.  Assessment of vulnerable atherosclerotic and fibrotic plaques in coronary arteries using 68Ga-DOTATATE PET/CT 
Activated macrophages which express somatostatin receptor-2 (SSTR-2) play a vital role in rupture of the vulnerable atherosclerotic plaques, which result in death. 68Ga-DOTATATE binds to somatostatin receptors 2, and therefore, can serve as potential radiotracer to detect atherosclerotic plaques. The purpose of this study was to generate preliminary data with this agent in vulnerable or fibrotic atherosclerotic plaques in the coronary arteries. We evaluated a total of 44 patients with neuroendocrine tumors (NET) who underwent 68Ga-DOTATATE PET/CT. In each subject, 7 segments in the coronary arteries were assessed, maximum SUV values and target-to-background ratios (TBRs) were calculated. The lesions detected by CT (a total of 308) were divided into 3 groups based on the Hounsfield unites (HU), and of which, 131 with HU less than 70 were classified as being normal (Control Group), 129 with HU 71-188 as fibrotic plaques (Group 2), and. 48 lesions with HU more than 188 as atherosclerotic plaques (Group 3). The mean TBR value in the normal group was 1.345 ± 0.58 while the mean TBR value in the fibrotic plaque group was 1.752 ± 1.50 (p 0.0043) and in atherosclerotic plaques group was (2.043 ± 1.76, p<0.0001). There was a significant correlation (p=0.0026) between 68Ga-DOTATATE uptake and the progression to formation of atherosclerotic plaques, based on HU. In patients with neuroendocrine tumors, 68Ga-DOTATATE PET/CT showed significantly increased uptake in the fibrotic and vulnerable atherosclerotic plaques compared to normal coronary arteries suggesting a potential role of this tracer for molecular assessment of coronary artery disease in this population.
PMCID: PMC4299775  PMID: 25625028
Atherosclerotic plaques; 68Ga-DOTATATE; somatostatin receptor; cardiovascular risk factors; macrophage
4.  A phase I study of an agonist CD40 monoclonal antibody (CP-870,893) in combination with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma 
This phase I study investigated the maximum-tolerated dose (MTD), safety, pharmacodynamics, immunological correlatives, and anti-tumor activity of CP-870,893, an agonist CD40 antibody, when administered in combination with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma (PDA).
Experimental Design
Twenty-two patients with chemotherapy-naïve advanced PDA were treated with 1000 mg/m2 gemcitabine once weekly for 3 weeks with infusion of CP-870,893 at 0.1 mg/kg or 0.2 mg/kg on day 3 of each 28 day cycle.
CP-870,893 was well-tolerated; one dose-limiting toxicity (grade 4 cerebrovascular accident) occurred at the 0.2 mg/kg dose level, which was estimated as MTD. The most common adverse event was cytokine release syndrome (grade 1 to 2). CP-870,893 infusion triggered immune activation marked by an increase in inflammatory cytokines, an increase in B cell expression of co-stimulatory molecules, and a transient depletion of B cells. Four patients achieved a partial response (PR). [18F]-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) demonstrated >25% decrease in FDG uptake within primary pancreatic lesions in 6 of 8 patients; however, responses observed in metastatic lesions were heterogeneous with some lesions responding with complete loss of FDG uptake while other lesions in the same patient failed to respond. Improved overall survival correlated with a decrease in FDG uptake in hepatic lesions (R = −0.929; p = 0.007).
CP-870,893 in combination with gemcitabine was well-tolerated and associated with anti-tumor activity in patients with PDA. Changes in FDG uptake detected on PET/CT imaging provide insight into therapeutic benefit. Phase II studies are warranted.
PMCID: PMC3834036  PMID: 23983255
Pancreatic cancer; immunotherapy; CD40; CP-870,893; PET imaging; heterogeneity
5.  Prediction of Survival by [18F]Fluorodeoxyglucose Positron Emission Tomography in Patients With Locally Advanced Non–Small-Cell Lung Cancer Undergoing Definitive Chemoradiation Therapy: Results of the ACRIN 6668/RTOG 0235 Trial 
Journal of Clinical Oncology  2013;31(30):3823-3830.
In this prospective National Cancer Institute–funded American College of Radiology Imaging Network/Radiation Therapy Oncology Group cooperative group trial, we hypothesized that standardized uptake value (SUV) on post-treatment [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) correlates with survival in stage III non–small-cell lung cancer (NSCLC).
Patients and Methods
Patients received conventional concurrent platinum-based chemoradiotherapy without surgery; postradiotherapy consolidation chemotherapy was allowed. Post-treatment FDG-PET was performed at approximately 14 weeks after radiotherapy. SUVs were analyzed both as peak SUV (SUVpeak) and maximum SUV (SUVmax; both institutional and central review readings), with institutional SUVpeak as the primary end point. Relationships between the continuous and categorical (cutoff) SUVs and survival were analyzed using Cox proportional hazards multivariate models.
Of 250 enrolled patients (226 were evaluable for pretreatment SUV), 173 patients were evaluable for post-treatment SUV analyses. The 2-year survival rate for the entire population was 42.5%. Pretreatment SUVpeak and SUVmax (mean, 10.3 and 13.1, respectively) were not associated with survival. Mean post-treatment SUVpeak and SUVmax were 3.2 and 4.0, respectively. Post-treatment SUVpeak was associated with survival in a continuous variable model (hazard ratio, 1.087; 95% CI, 1.014 to 1.166; P = .020). When analyzed as a prespecified binary value (≤ v > 3.5), there was no association with survival. However, in exploratory analyses, significant results for survival were found using an SUVpeak cutoff of 5.0 (P = .041) or 7.0 (P < .001). All results were similar when SUVmax was used in univariate and multivariate models in place of SUVpeak.
Higher post-treatment tumor SUV (SUVpeak or SUVmax) is associated with worse survival in stage III NSCLC, although a clear cutoff value for routine clinical use as a prognostic factor is uncertain at this time.
PMCID: PMC3795891  PMID: 24043740
6.  The role of molecular imaging in diagnosis of deep vein thrombosis 
Venous thromboembolism (VTE) mostly presenting as deep venous thrombosis (DVT) and pulmonary embolism (PE) affects up to 600,000 individuals in United States each year. Clinical symptoms of VTE are nonspecific and sometimes misleading. Additionally, side effects of available treatment plans for DVT are significant. Therefore, medical imaging plays a crucial role in proper diagnosis and avoidance from over/under diagnosis, which exposes the patient to risk. In addition to conventional structural imaging modalities, such as ultrasonography and computed tomography, molecular imaging with different tracers have been studied for diagnosis of DVT. In this review we will discuss currently available and newly evolving targets and tracers for detection of DVT using molecular imaging methods.
PMCID: PMC4138136  PMID: 25143860
FDG-PET/CT; venous thromboembolism; deep vein thrombosis; SPECT; molecular imaging
7.  Clinical impact of FDG-PET/CT on colorectal cancer staging and treatment strategy 
FDG-PET/CT is rarely used for initial staging of patients with colorectal cancer (CRC). Surgical resection of primary tumor and isolated metastases may result in long-term survival or presumed cure, whereas disseminated disease contraindicates operation. We analyzed a retrospective material to elucidate the potential value of FDG-PET/CT for staging of CRC. Data were retrieved from 67 consecutive patients (24-84 years) with histopathologically proven CRC who had undergone FDG-PET/CT in addition to conventional imaging for initial staging. Treatment plans before and after FDG-PET/CT were compared and patients divided as follows: (A) Patients with a change in therapy following FDG-PET/CT and (B) Patients without a change following FDG-PET/CT. Sixty-two patients had colon and five had rectal cancer. Of these, 20 (30%; CI 20.2-41.7) belonged to group A, whereas 47 (70%; CI 58.3-79.8) fell in group B. In conclusion, FDG-PET/CT changed treatment plan in 30% of cases. In ⅓ of these there was either a change from intended curative to palliative therapy or vice versa, while in the remaining ⅔ the pattern was more mixed. Thus, even in a retrospective routine material there were substantial changes in management strategy following FDG-PET/CT for staging in CRC.
PMCID: PMC4138141  PMID: 25143865
FDG-PET/CT; colorectal cancer; clinical impact; treatment strategy
8.  GC-ASM: Synergistic Integration of Graph-Cut and Active Shape Model Strategies for Medical Image Segmentation 
Image segmentation methods may be classified into two categories: purely image based and model based. Each of these two classes has its own advantages and disadvantages. In this paper, we propose a novel synergistic combination of the image based graph-cut (GC) method with the model based ASM method to arrive at the GC-ASM method for medical image segmentation. A multi-object GC cost function is proposed which effectively integrates the ASM shape information into the GC framework. The proposed method consists of two phases: model building and segmentation. In the model building phase, the ASM model is built and the parameters of the GC are estimated. The segmentation phase consists of two main steps: initialization (recognition) and delineation. For initialization, an automatic method is proposed which estimates the pose (translation, orientation, and scale) of the model, and obtains a rough segmentation result which also provides the shape information for the GC method. For delineation, an iterative GC-ASM algorithm is proposed which performs finer delineation based on the initialization results. The proposed methods are implemented to operate on 2D images and evaluated on clinical chest CT, abdominal CT, and foot MRI data sets. The results show the following: (a) An overall delineation accuracy of TPVF > 96%, FPVF < 0.6% can be achieved via GC-ASM for different objects, modalities, and body regions. (b) GC-ASM improves over ASM in its accuracy and precision to search region. (c) GC-ASM requires far fewer landmarks (about 1/3 of ASM) than ASM. (d) GC-ASM achieves full automation in the segmentation step compared to GC which requires seed specification and improves on the accuracy of GC. (e) One disadvantage of GC-ASM is its increased computational expense owing to the iterative nature of the algorithm.
PMCID: PMC3622953  PMID: 23585712
Object Recognition; Image Segmentation; Statistical Shape Models; Graph Cut
9.  Quantification of Atherosclerotic Plaque Activity and Vascular Inflammation using [18-F] Fluorodeoxyglucose Positron Emission Tomography (PET)/Computed Tomography (CT) 
Conventional non-invasive imaging modalities of atherosclerosis such as coronary artery calcium (CAC)1 and carotid intimal medial thickness (C-IMT)2 provide information about the burden of disease. However, despite multiple validation studies of CAC3–5, and C-IMT2,6, these modalities do not accurately assess plaque characteristics7,8, and the composition and inflammatory state of the plaque determine its stability and, therefore, the risk of clinical events9–13.
[18F]-2-fluoro-2-deoxy-D-glucose (FDG) imaging using positron-emission tomography (PET)/computed tomography (CT) has been extensively studied in oncologic metabolism14,15. Studies using animal models and immunohistochemistry in humans show that FDG-PET/CT is exquisitely sensitive for detecting macrophage activity16, an important source of cellular inflammation in vessel walls. More recently, we17,18 and others have shown that FDG-PET/CT enables highly precise, novel measurements of inflammatory activity of activity of atherosclerotic plaques in large and medium-sized arteries9,16,19,20. FDG-PET/CT studies have many advantages over other imaging modalities: 1) high contrast resolution; 2) quantification of plaque volume and metabolic activity allowing for multi-modal atherosclerotic plaque quantification; 3) dynamic, real-time, in vivo imaging; 4) minimal operator dependence. Finally, vascular inflammation detected by FDG-PET/CT has been shown to predict cardiovascular (CV) events independent of traditional risk factors21,22 and is also highly associated with overall burden of atherosclerosis23. Plaque activity by FDG-PET/CT is modulated by known beneficial CV interventions such as short term (12 week) statin therapy24 as well as longer term therapeutic lifestyle changes (16 months)25.
The current methodology for quantification of FDG uptake in atherosclerotic plaque involves measurement of the standardized uptake value (SUV) of an artery of interest and of the venous blood pool in order to calculate a target to background ratio (TBR), which is calculated by dividing the arterial SUV by the venous blood pool SUV. This method has shown to represent a stable, reproducible phenotype over time, has a high sensitivity for detection of vascular inflammation, and also has high inter-and intra-reader reliability26. Here we present our methodology for patient preparation, image acquisition, and quantification of atherosclerotic plaque activity and vascular inflammation using SUV, TBR, and a global parameter called the metabolic volumetric product (MVP). These approaches may be applied to assess vascular inflammation in various study samples of interest in a consistent fashion as we have shown in several prior publications9,20,27,28
PMCID: PMC3466935  PMID: 22588186
FDG-PET/CT; atherosclerosis; vascular inflammation; quantitative radiology
11.  A comparison of vascular inflammation in psoriasis, rheumatoid arthritis, and healthy subjects by FDG-PET/CT: a pilot study 
Objective: Psoriasis (PSO) and rheumatoid arthritis (RA) increase cardiovascular diseases (CVD) beyond traditional risk factors. Vascular inflammation has previously been demonstrated to be present in PSO and RA using [18F]-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging. However, vascular inflammation has not been compared in these two disorders relative to a healthy reference population. Thus, vascular inflammation was quantitatively assessed in patients with PSO (n=10), RA (n=5), and healthy subjects (n=10) using FDG-PET/CT. Methods: FDG-PET/CT mean standardized uptake value (SUVmean) was determined slice by slice within the ascending, aortic arch, descending thoracic, suprarenal abdominal, and infrarenal abdominal aorta, and the mean metabolic volumetric product (MVPmean) was then calculated for each aortic subsegment. Plasma lipids and metabolic and inflammatory markers were also assessed. Results: CVD risk profiles were largely similar across groups. After adjustment for CV risk factors, regional aortic vascular inflammation based on MVPmean was elevated for both PSO (beta coefficients 0.31-1.47, p<0.001) and RA (beta coefficients 0.15-0.69, p<0.05) compared to healthy subjects. Conclusions: These observations using FDG-PET/CT to estimate vascular inflammation support epidemiological findings of premature atherosclerosis in PSO and RA. The use of FDG-PET/CT to investigate vascular inflammation across systemic inflammatory diseases warrants further examination in larger study populations.
PMCID: PMC3819587  PMID: 24224139
Psoriasis; rheumatoid arthritis; atherosclerosis; vascular inflammation; FDG-PET/CT
12.  Amyloid-β Positron Emission Tomography Imaging Probes: A Critical Review 
The rapidly rising prevalence and cost of Alzheimer’s disease (AD) in recent decades has made the imaging of amyloid-β (Aβ) deposits the focus of intense research. Several amyloid imaging probes with purported specificity for Aβ plaques are currently at various stages of FDA approval. However, a number of factors appear to preclude these probes from clinical utilization. As the available “amyloid specific” PET imaging probes have failed to demonstrate diagnostic value and have shown limited utility for monitoring therapeutic interventions in humans, a debate on their significance has emerged. The aim of this review is to identify and discuss critically the scientific issues contributing to the extensive inconsistencies reported in the literature on their purported in vivo amyloid specificity and potential utilization in patients.
PMCID: PMC3740015  PMID: 23648516
amyloid imaging; amyloid ‘specific’ imaging probes; Amyvid; PIB; critical review; neuropathologic criteria; silent medial temporal lobe
13.  Direct Comparison of FDG-PET and ASL-MRI in Alzheimer’s Disease 
The utility flourodeoxyglucose PET (FDG-PET) imaging in Alzheimer’s Disease (AD) diagnosis is well established. Recently, measurement of cerebral blood flow using arterial spin labeling MRI (ASL-MRI) has shown diagnostic potential in AD, though it has never been directly compared to FDG-PET.
We employed a novel imaging protocol to obtain FDG-PET and ASL-MRI images concurrently in 17 AD patients and 19 age-matched controls. Paired FDG-PET and ASL-MRI images from 19 controls and 15 AD patients were included for qualitative analysis, while paired images 18 controls and 13 AD patients were suitable for quantitative analyses.
The combined imaging protocol was well tolerated. Both modalities revealed very similar regional abnormalities in AD, as well as comparable sensitivity and specificity for the detection of AD following visual review by two expert readers. Interobserver agreement was better for FDG-PET (kappa 0.75, SE 0.12) than ASL-MRI (kappa 0.51, SE 0.15), intermodality agreement was moderate to strong (kappa 0.45-0.61), and readers were more confident of FDG-PET reads. Simple quantitative analysis of global cerebral FDG uptake (FDG-PET) or whole brain cerebral blood flow (ASL-MRI) showed excellent diagnostic accuracy for both modalities, with area under ROC curves of 0.90 for FDG-PET (95% CI 0.79-0.99) and 0.91 for ASL-MRI (95% CI 0.80-1.00).
Our results demonstrate that FDG-PET and ASL-MRI identify similar regional abnormalities and have comparable diagnostic accuracy in a small population of AD patients, and support the further study of ASL-MRI in dementia diagnosis.
PMCID: PMC3264701  PMID: 22018493
ASL; FDG; PET; MRI; Alzheimer’s disease; spin label; fluorodeoxyglucose; dementia
14.  Post-Surgical Atypical FDG-PET Uptake 
Clinical nuclear medicine  2009;34(11):808-810.
False positive recognition is crucial for proper interpretation of FDG-PET studies. The authors present a case of a woman who underwent surgery over a month prior to PET/CT imaging which revealed significant tracer uptake within muscles and soft tissue in several sites contralateral to the location of surgery. The FDG-PET images of this case illustrate the importance of communication between physicians ordering and physicians reading FDG-PET/CT scans as well as atypical FDG-PET findings that could be interpreted as concerning but are, in fact, innocuous. This study also demonstrates the unusual glucose metabolic patterns which may arise following treatment be it surgical, chemotherapeutic or radiation.
PMCID: PMC3530922  PMID: 19851183
positron emission tomography; fluorodeoxyglucose; inflammation; post-surgical changes
15.  Evaluation of 18F-FDG PET and MRI Associations in Pediatric Diffuse Intrinsic Brain stem Glioma: A Report from the Pediatric Brain Tumor Consortium 
To assess 18F-labeled 2-fluoro-2-deoxy-D-glucose (18F-FDG) uptake in children with a newly diagnosed diffuse intrinsic brainstem glioma (BSG) and to investigate associations with progression-free survival (PFS), overall survival (OS) and MRI indices.
Two Pediatric Brain Tumor Consortium (PBTC) therapeutic trials in children with newly diagnosed BSG were designed to test radiation therapy combined with molecularly targeted agents (PBTC-007: Phase I/II study of gefitinib; PBTC-014: Phase I/II study of tipifarnib). Baseline brain 18F-FDG PET scans were obtained in 40 children in these trials. Images were evaluated by consensus of two PET experts for intensity and uniformity of tracer uptake. Associations of 18F-FDG uptake intensity and uniformity with both PFS and OS were evaluated as well as associations with tumor MRI indices at baseline (tumor volume on FLAIR, baseline intratumoral enhancement, diffusion and perfusion values.
In the majority of children, BSG 18F-FDG uptake was less than gray matter uptake. Survival was poor irrespective of intensity of 18F-FDG uptake, with no association between intensity of 18F-FDG uptake and PFS or OS. However, hyperintense 18F-FDG uptake in tumor compared to gray matter suggested poorer survival rates. Patients with 18F-FDG uptake in ≥ 50% of the tumor had shorter PFS and OS compared to patients with 18F-FDG uptake in < 50% of tumor. There was some evidence that tumors with higher 18F-FDG uptake were more likely to show enhancement; and when the diffusion ratio was lower the uniformity of 18F- FDG uptake appeared higher.
Children with BSG where 18F-FDG uptake involves at least half the tumor appear to have inferior survival compared to children with uptake in <50% of tumor. A larger independent study is needed to verify this hypothesis. Intense tracer uptake in the tumors compared to gray matter suggests decreased survival. Higher 18F-FDG uptake within the tumor was associated with enhancement on MRI. Increased tumor cellularity as reflected by restricted MR diffusion may be associated with increased 18F-FDG uniformity throughout the tumor.
PMCID: PMC3526809  PMID: 21233173
pediatric; brainstem glioma; 18F-FDG PET; MRI; diffusion; enhancement; perfusion; brain tumor
16.  Aortic vascular inflammation in psoriasis is associated with HDL particle size and concentration: a pilot study 
Psoriasis is a model Th1-mediated inflammatory disease associated with increased incidence of stroke and cardiovascular disease (CVD). The mechanism behind these associations is unknown, however abnormal HDL particle composition measured by nuclear magnetic resonance (NMR) spectroscopy has been shown to be associated with CVD. Using [18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT), a validated surrogate marker of CVD, we assessed whether HDL particle size and concentration were associated with vascular inflammation in patients with psoriasis. Patients with psoriasis were prospectively enrolled (439 aortic samples from 10 patients). Lipoprotein profiles using NMR spectroscopy were obtained and the relationship between vascular inflammation within the thoracic aorta by FDG-PET/CT was analyzed for association with lipoprotein particle characteristics. The plasma total cholesterol (206 mg/dL (IQR 154-229)), LDL (105 (90-161)), and triglyceride levels were within normal range (151 (94-191)) while HDL levels were low (28.9 (27.2-31.3)); however, the NMR profile demonstrated an atherogenic profile with increased small LDL and HDL particles. Total HDL particle concentration (p<0.001) and HDL particle size (p<0.001) were associated with decreased aortic inflammation, while concentration of small HDL particles was associated with increased inflammation (p<0.001). The association of total HDL particle concentration (β -0.0113, p=0.002) and small HDL particle concentration (β 0.026, p<0.001) with aortic inflammation persisted following adjustment for CVD risk factors. Total HDL particle concentration and small HDL particle concentration were associated with vascular inflammation within the thoracic aorta in psoriasis. These findings suggest that HDL particle characteristics may play an important role in psoriatic vascular inflammation and CVD.
PMCID: PMC3499940  PMID: 23173102
Psoriasis; inflammation; atherosclerosis; high-density lipoprotein cholesterol particle; FDG PET CT
19.  Emerging role of radiolabeled nanoparticles as an effective diagnostic technique 
EJNMMI Research  2012;2:39.
Nanomedicine is emerging as a promising approach for diagnostic applications. Nanoparticles are structures in the nanometer size range, which can present different shapes, compositions, charges, surface modifications, in vitro and in vivo stabilities, and in vivo performances. Nanoparticles can be made of materials of diverse chemical nature, the most common being metals, metal oxides, silicates, polymers, carbon, lipids, and biomolecules. Nanoparticles exist in various morphologies, such as spheres, cylinders, platelets, and tubes. Radiolabeled nanoparticles represent a new class of agent with great potential for clinical applications. This is partly due to their long blood circulation time and plasma stability. In addition, because of the high sensitivity of imaging with radiolabeled compounds, their use has promise of achieving accurate and early diagnosis. This review article focuses on the application of radiolabeled nanoparticles in detecting diseases such as cancer and cardiovascular diseases and also presents an overview about the formulation, stability, and biological properties of the nanoparticles used for diagnostic purposes.
PMCID: PMC3441881  PMID: 22809406
nanoparticles; PET imaging; SPECT imaging; tumor; inflammation; cardiovascular disease
20.  The Value of Radiologic Interventions and 18F-DOPA PET in Diagnosing and Localizing Focal Congenital Hyperinsulinism: Systematic Review and Meta-Analysis 
Molecular Imaging and Biology  2012;15(1):97-105.
This systematic review and meta-analysis aimed to quantify the diagnostic performance of pancreatic venous sampling (PVS), selective pancreatic arterial calcium stimulation with hepatic venous sampling (ASVS), and 18F-DOPA positron emission tomography (PET) in diagnosing and localizing focal congenital hyperinsulinism (CHI).
This systematic review and meta-analysis was conducted according to the PRISMA statement. PubMed, EMBASE, SCOPUS and Web of Science electronic databases were systematically searched from their inception to November 1, 2011. Using predefined inclusion and exclusion criteria, two blinded reviewers selected articles. Critical appraisal ranked the retrieved articles according to relevance and validity by means of the QUADAS-2 criteria. Pooled data of homogeneous study results estimated the sensitivity, specificity, likelihood ratios and diagnostic odds ratio (DOR).
18F-DOPA PET was superior in distinguishing focal from diffuse CHI (summary DOR, 73.2) compared to PVS (summary DOR, 23.5) and ASVS (summary DOR, 4.3). Furthermore, it localized focal CHI in the pancreas more accurately than PVS and ASVS (pooled accuracy, 0.82 vs. 0.76, and 0.64, respectively). Important limitations comprised the inclusion of studies with small sample sizes, high probability of bias and heterogeneity among their results. Studies with small sample sizes and high probability of bias tended to overestimate the diagnostic accuracy.
This systematic review and meta-analysis found evidence for the superiority of 18F-DOPA PET in diagnosing and localizing focal CHI in patients requiring surgery for this disease.
PMCID: PMC3553406  PMID: 22752652
Congenital hyperinsulinism; Pancreatic venous sampling; Arterial stimulation venous sampling; 18F-DOPA PET; Positron emission tomography; Diagnosis
21.  Systemic and Vascular Inflammation in Patients with Moderate to Severe Psoriasis as measured by [18F]-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT): A Pilot Study 
Archives of dermatology  2011;147(9):1031-1039.
To evaluate the feasibility of utilizing [18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) to detect and quantify systemic inflammation in psoriasis patients.
Case series with a nested case-control study.
Referral dermatology and preventive cardiology practices.
Six patients with psoriasis affecting >10% body surface area and 4 controls age and sex matched to 4 psoriasis patients for a nested case-control study.
Main Outcome Measures
FDG uptake in the liver, musculoskeletal structures, and aorta measured by mean Standardized Uptake Value (SUV), a measure of FDG tracer uptake by macrophages and other inflammatory cells.
FDG-PET/CT identified numerous foci of inflammation in 6 patients with psoriasis within the skin, liver, joints, tendons, and aorta. Inflammation in the joints was observed in a patient with psoriatic arthritis as well as in 1 patient with no history of joint disease or joint symptoms. In a nested case-control study, FDG-PET/CT imaging demonstrated increased vascular inflammation in multiple segments of the aorta compared to controls. These findings persisted after adjustment for traditional cardiovascular risk factors in multivariate analysis (mean beta 0.33, p<0.001). Patients with psoriasis further demonstrated increased hepatic inflammation after adjusting for cardiovascular risk factors (beta 0.18, p<0.001), but the association was no longer significant when adjusted for alcohol intake (beta −0.25, p=0.07).
FDG-PET/CT is a sensitive tool for identifying inflammation and can be used to identify clinically observed inflammation in the skin and subclinical inflammation in the blood vessels, joints, and liver of patients with psoriasis.
PMCID: PMC3158301  PMID: 21576552
24.  Gd3+-DTPA-DG: novel nanosized dual anticancer and molecular imaging agent 
Difficulties in the use, preparation, and cost of radioactively-labeled glycosylated compounds led to this research and development study of a new gadolinium-labeled glucose compound that does not have a radioactive half-life or difficulties in its synthesis and utilization.
Based on the structure of the 2-fluoro-2-deoxy-D-glucose molecule (18FDG), a new compound consisting of D-glucose (1.1 nm) conjugated to a well-known chelator, diethylenetriamine penta-acetic acid (DTPA), was synthesized, labeled with Gd3+, and examined in vitro and in vivo.
This novel compound not only demonstrated excellent and less costly imaging capability, but also showed anticancer effects on treated cells. Our results demonstrated that the new Gd3+-DTPA-DG compound (GDD, with GDD conjugate aggregation of about 8 nm at 0.02 mg/mL concentration) significantly decreased HT1080 and HT29 tumor cell numbers. Application of GDD to cancer cells also increased levels of tumor necrosis factor alpha, but did not alter blood glucose levels. Interestingly, no toxicological findings were seen in normal human kidney cells.
Dual application of GDD for both imaging and treatment of tumor cells could be remarkably advantageous in both the diagnosis and treatment of cancer.
PMCID: PMC3090272  PMID: 21589643
fluorodeoxyglucose; Gd3+-DTPA-DG; positron emission tomography; diagnostics; treatment
25.  Role of Imaging in Prostate Cancer 
PET clinics  2009;4(2):135-138.
PMCID: PMC2746671  PMID: 20161047

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