Kyung-Han Lee

Improved Detection of Second Primary Cancer Using Integrated [18F] Fluorodeoxyglucose Positron Emission Tomography and Computed Tomography for Initial Tumor Staging

PURPOSE This study evaluated prospectively the value of integrated whole-body positron emission tomography and computed tomography (PET/CT) using [18F] fluorodeoxyglucose (FDG) in detecting a second primary cancer at the time of the initial staging in comparison with a conventional staging work-up (CSW). METHODS The participants were 547 patients diagnosed with cancer who underwent FDG PET/CT imaging for the initial staging. An additional diagnostic evaluation was performed when there were abnormal findings indicative of a second primary cancer on either PET/CT or CSW considering the site and the biologic behavior of the alleged primary tumor. RESULTS A total of 27 second primary malignant tumors were identified in 26 of the 547 patients (4.8%). FDG PET/CT found 45 lesions indicative of a second primary cancer, of which 24 lesions were proved to be a second primary cancer, seven were clinically unexpected metastases, and 14 lesions were benign. Therefore, sensitivity and positive predictive value of FDG PET/CT in detecting a second primary cancer or an unexpected metastasis were 91% (31 of 34) and 69% (31 of 45), respectively. In contrast, CSW could not identify 16 second primary cancers and one metastatic lesion. CONCLUSION FDG PET/CT at the time of the initial staging is useful for screening a second primary cancer with a high sensitivity. An additional diagnostic work-up is essential when abnormal findings, which are indicative of a second primary cancer, are obtained on PET/CT images to rule out the presence of either a second primary cancer or an unexpected metastasis.

Prognostic value of 18F-FDG PET/CT in patients with squamous cell carcinoma of the tonsil: comparisons of volume-based metabolic parameters.

The prognostic significance of volume‐based metabolic parameters measured by 18F‐fluorodeoxyglucose positron emission tomography/CT (18F‐FDG PET/CT) is not established. We evaluated the prognostic value of metabolic parameters in patients with squamous cell carcinoma (SCC) of the tonsil.

Prognostic Significance of Vascular Endothelial Growth Factor Expression and Microvessel Density in Esophageal Squamous Cell Carcinoma: Comparison With Positron Emission Tomography

BackgroundThis study investigated whether the expression of vascular endothelial growth factor (VEGF) in a primary tumor and the intratumoral microvessel density (MVD) were independent prognostic factors in patients with an esophageal squamous cell carcinoma (SCC) in comparison with positron emission tomography (PET) by using 18F-fluorodeoxyglucose (FDG) and stage.MethodsFifty-one patients with a newly diagnosed esophageal SCC who underwent preoperative FDG-PET and esophagectomy with intent to cure were enrolled in this study. The VEGF expression level, the intratumoral MVD, and the Ki-67 labeling index were evaluated by using immunohistochemical staining. Only significant variables in the univariate survival analysis were examined by multivariate survival analysis with the Cox proportional hazards model.ResultCancer-related deaths occurred in 17 of 51 patients during the follow-up. Univariate survival analysis showed that the pathologic stage, pNM, maximum standardized uptake value of the primary tumor, tumor length on PET, number of PET-positive lymph nodes, PET stage, Ki-67 labeling index, intratumoral MVD, and the presence of VEGF expression were significant prognostic predictors for the overall survival. Multivariate analysis revealed that the pathologic stage, number of PET-positive nodes (0, 1, 2, or ≥3), intratumoral MVD (cutoff, 60/mm2), and presence of VEGF expression were independent significant prognostic predictors for overall survival.ConclusionIn addition to the pathologic stage, the intratumoral MVD, the presence of VEGF expression, and the number of FDG-PET–positive nodes were independent prognostic predictors in patients with an esophageal SCC undergoing curative surgery.

Up-Regulation of Insulin-Like Growth Factor-II Expression Is a Feature of TrkA but Not TrkB Activation in SH-SY5Y Neuroblastoma Cells

The types of neurotrophin receptors that are expressed in neuroblastomas have different prognostic implications; trkA is a marker of good prognosis, whereas trkB expression is associated with poor prognosis. This suggests that either the signaling that is mediated via these receptors modulates the biological features of neuroblastoma cells differently, or that distinct lineages of sympathoadrenal precursors have been transformed. In this report, we evaluate the biological effects after activation of trkA or trkB by their major ligands in SH-SY5Y human neuroblastoma cells. Both trkA and trkB induce differentiation, inhibit growth, and promote the survival of cells under conditions of nutrient deprivation. However, the up-regulation of insulin-like growth factor-II (IGF-II) expression is a predominant feature of trkA activation by nerve growth factor (NGF). The growth inhibition induced by blocking the insulin-like growth factor-I receptor suggests that IGF-II is a component of the effector mechanism of trkA activation by NGF in trkA-transfected cells. Although trkA and trkB expression is associated with different prognoses in neuroblastoma, our study indicates that the effects mediated by these receptors in vivo may be quite similar for certain subsets of neuroblastomas.

Relation of Carotid Artery 18F-FDG Uptake to C-Reactive Protein and Framingham Risk Score in a Large Cohort of Asymptomatic Adults

We investigated the relation of carotid 18F-FDG uptake to high-sensitivity C-reactive protein (hsCRP) and Framingham risk score (FRS) in a large cohort of asymptomatic adults. Methods: Carotid artery 18F-FDG uptake was measured on the PET/CT scans of 1,181 asymptomatic subjects, and maximum target-to-background ratio (M-TBR) and intima-media thickness (IMT) were compared with clinical risk factors and hsCRP. The estimated 10-y risk for general cardiovascular disease was calculated by FRS. Results: FRS increased from 11.5% ± 7.8% to 14.8% ± 10.5% in subjects with an M-TBR ≥ 1.7, compared with < 1.7, and the odds ratio for an FRS ≥ 10% was 1.9 (95% confidence interval [CI], 1.4–2.5). Adjusting for age confirmed a significant association of M-TBR and IMT with FRS. Independent determinants of high M-TBR were abdominal fat (β coefficient [B], 1.1040; P < 0.0001), low-density lipoprotein (LDL) (B, 0.0006; P < 0.05), and FRS (B, 0.0025; P < 0.05) for subjects < 50 y and abdominal fat (B, 0.9740; P < 0.0001), age (B, 0.0040; P = 0.0001), LDL (B, 0.0008; P = 0.0001), and IMT (B, 0.1097; P < 0.01) for subjects ≥ 50 y. Although hsCRP also stratified subjects for FRS-based risk, no correlation was found between hsCRP and M-TBR or IMT, suggesting that they may have different inferences. Importantly, in the low-hsCRP (14.2% ± 9.7% vs. 11.3% ± 7.4%) and high-hsCRP groups (18.8% ± 14.3% vs. 13.3% ± 10.2%), FRS was significantly greater for subjects with high M-TBR than for those with low M-TBR. The odds ratio for FRS ≥ 10% between subjects with high and low M-TBR was 1.20 (95% CI, 0.90–1.60; P = 0.209) in the low-hsCRP group and 2.95 (95% CI, 1.48–5.86; P = 0.002) in the high-hsCRP group. Conclusion: High carotid 18F-FDG uptake in asymptomatic adults is associated with increased clinical risk factors and FRS. Furthermore, it appears to reflect aspects of atherosclerotic inflammation distinct from hsCRP concentration and may offer incremental information regarding cardiovascular risk.

Oxidized Low-Density Lipoprotein Stimulates Macrophage 18F-FDG Uptake via Hypoxia-Inducible Factor-1α Activation Through Nox2-Dependent Reactive Oxygen Species Generation

For 18F-FDG PET to be widely used to monitor atherosclerosis progression and therapeutic response, it is crucial to better understand how macrophage glucose metabolism is influenced by the atherosclerotic microenvironment and to elucidate the molecular mechanisms of this response. Oxidized low-density lipoprotein (oxLDL) is a key player in atherosclerotic inflammation that promotes macrophage recruitment, activation, and foam cell formation. We thus explored the effect of oxLDL on macrophage 18F-FDG uptake and investigated the underlying molecular mechanism including the roles of hypoxia-inducible factor-1α (HIF-1α) and reactive oxygen species (ROS). Methods: RAW264.7 macrophages were stimulated with native LDL, oxLDL, or lipopolysaccharide. Cells were assessed for 18F-FDG uptake, lactate production, membrane glucose transporter 1 (GLUT1) expression, and hexokinase activity. ROS generation, Nox expression, and HIF-1α activity were also measured. Results: oxLDL (20 μg/mL) induced a 17.5 ± 1.7-fold increase in macrophage 18F-FDG uptake by 24 h, which was accompanied by increased lactate production, membrane GLUT1 expression, and hexokinase activity. oxLDL-stimulated 18F-FDG uptake was completely blocked by inhibitors of Src or phosphoinositide 3-kinase. ROS generation was increased to 262.4% ± 17.9% of controls by oxLDL, and N-acetyl-l-cysteine completely abrogated both oxLDL-induced ROS production and 18F-FDG uptake. oxLDL increased Nox2 expression, and nicotinamide adenine dinucleotide phosphate oxidase inhibition totally blocked increased ROS generation and 18F-FDG uptake by oxLDL. Finally, there was a clear ROS-dependent increase of HIF-1α accumulation by oxLDL, and silencing of HIF-1α completely abolished the metabolic effect of oxLDL. Conclusion: oxLDL is a strong stimulator of macrophage 18F-FDG uptake and glycolysis through upregulation of GLUT1 and hexokinase. This metabolic response is mediated by Nox2-dependent ROS generation that promotes HIF-1α activation.

Cognitive deficits of pure subcortical vascular dementia vs Alzheimer disease PiB-PET–based study

Objectives: Despite many neuropsychological studies to differentiate subcortical vascular dementia (SVaD) from Alzheimer disease (AD), previous studies did not eliminate confounding effects of mixed Alzheimer and vascular pathology. We aimed to investigate neuropsychological differences between patients with Pittsburgh compound B (PiB)–negative SVaD and those with PiB-positive AD. Methods: We recruited patients who were clinically diagnosed with SVaD or AD and underwent an 11C-PiB-PET scan. All patients with SVaD fulfilled DSM-IV criteria for vascular dementia and had severe white matter hyperintensities. The diagnosis of AD was made on the basis of criteria for probable AD proposed by the National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association. Results: The final patient sample consisted of 44/67 (65.7%) patients with SVaD who tested negative for PiB retention [PiB(−) SVaD] and 61/68 (89.7%) patients with AD who tested positive for PiB retention [PiB(+) AD]. Patients with PiB(−) SVaD performed better than patients with PiB(+) AD on both verbal and visual memory tests including delayed recalls of the Seoul Verbal Learning Test and Rey Complex Figure Test. Patients with PiB(−) SVaD were worse than patients with PiB(+) AD on phonemic fluency of the Controlled Oral Word Association Test and Stroop color test. Conclusions: Patients with PiB(−) SVaD were better at memory but worse at frontal function than patients with PiB(+) AD. The differences in memory/frontal functions observed between the 2 groups, however, could not differentiate all individual data due to some overlap in the cutoff threshold.

Optimization of pinhole collimator for small animal SPECT using Monte Carlo simulation

The aim of this study is to design an optimized pinhole collimator using Monte Carlo simulation for the development of an ultra high-resolution SPECT using a position sensitive photo-multiplier tube. Simulations using Monte Carlo N-Particle Transport code, version 4c were performed to model the pinhole SPECT system. The simulation geometries consist of a cone-shaped pinhole collimator with tungsten aperture and a NaI(Tl) scintillation crystal measuring 6 mm in thickness and 120 mm in diameter. Spatial resolution, sensitivity, edge penetration, and scatter fraction were simulated by changing the pinhole diameter and channel height. The optimal ranges of pinhole diameter and channel height were determined from tradeoff curves of resolution and sensitivity and from penetration and scatter fraction. Tradeoff curves allowed us to determine the optimal range of pinhole diameter to be from 1 mm to 1.5 mm for the system configured in this study. The penetration and scatter fraction curve indicated that the channeled aperture was preferable over knife-edge. The optimal range of channel height was from 0.3 to 0.6 mm. The results demonstrate that the pinhole collimator designed in this study could be utilized to perform ultra high-resolution small animal imaging.

Tumor-Homing Glycol Chitosan-Based Optical/PET Dual Imaging Nanoprobe for Cancer Diagnosis

Imaging techniques including computed tomography, magnetic resonance imaging, and positron emission tomography (PET) offer many potential benefits to diagnosis and treatment of cancers. Each method has its own strong and weak points. Therefore, multimodal imaging techniques have been highlighted as an alternative method for overcoming the limitations of each respective imaging method. In this study, we fabricated PET/optical activatable imaging probe based on glycol chitosan nanoparticles (CNPs) for multimodal imaging. To prepare the dual PET/optical probes based on CNPs, both (64)Cu radiolabeled DOTA complex and activatable matrix metalloproteinase (MMP)-sensitive peptide were chemically conjugated onto azide-functionalized CNPs via bio-orthogonal click chemistry, which was a reaction between azide group and dibenzyl cyclooctyne. The PET/optical activatable imaging probes were visualized by PET and optical imaging system. Biodistribution of probes and activity of MMP were successfully measured in tumor-bearing mice.

Effects of atorvastatin pretreatment on infarct size in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

BACKGROUND Atorvastatin pretreatment has been reported to reduce myocardial damage in patients undergoing percutaneous coronary intervention (PCI). We sought to investigate the effect of atorvastatin pretreatment on infarct size in patients with ST-segment elevation myocardial infarction (STEMI). METHODS Patients undergoing primary PCI for ST-segment elevation myocardial infarction within 12 hours after symptom onset were randomized to an atorvastatin group (80 mg before PCI and for 5 days after PCI [n = 89]) or a control group (10 mg daily after PCI [n = 84]). The primary end point was infarct size measured by technetium Tc 99m tetrofosmin single-photon emission computed tomography between days 5 and 14. RESULTS Baseline clinical, angiographic, and procedural characteristics were not significantly different between groups except for age and current smoking status. There was no significant difference in infarct size (as a percentage of the left ventricle) between groups (22.2% ± 15.5% in the atorvastatin group vs 21.6% ± 15.4% in the control group, P = .79). The median infarct size was 19.0% (interquartile range 9.0-32.0) in the atorvastatin group and 18.0% (9.3-32.5) in the control group (P = .76). Achievement of myocardial blush grade 2/3 and complete ST-segment resolution at 60 minutes after PCI occurred with similar frequency (72.8% vs 81.9%, P = .33 and 43.2% vs 47.5%, P = .57, respectively). CONCLUSIONS Pretreatment with high-dose atorvastatin followed by further treatment for 5 days did not reduce infarct size measured by single-photon emission computed tomography in patients undergoing primary PCI.