Kisoo Pahk

Correlation between Semi-Quantitative (18)F-FDG PET/CT Parameters and Ki-67 Expression in Small Cell Lung Cancer.

PurposeThe aim of this study was to evaluate the relationship between semiquantitative parameters on 18F-FDG PET/CT including maximum standardized uptake value (SUVmax), mean standardized uptake value (SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) and the expression level of Ki-67 in small-cell lung cancer (SCLC).MethodsNinety-four consecutive patients with SCLC were enrolled in this study. They underwent 18F-FDG PET/CT for initial evaluation of SCLC, and we measured SUVmax, avgSUVmean, MTVsum, and TLGtotal on 18F-FDG PET/CT images. The protein expression of Ki-67 was examined by immunohistochemical staining.ResultsSignificant correlations were found between the MTVsum and Ki-67 labeling index (r = 0.254, p = 0.014) and the TLGtotal and Ki-67 labeling index (r = 0.239, p = 0.020). No correlation was found between the SUVmax and Ki-67 labeling index (r = 0.116, p = 0.264) and the avgSUVmean and Ki-67 labeling index (r = 0.031, p = 0.770). Dividing the Ki-67 expression level into three categories, it was suggested that increasing Ki-67 expression level caused a stepwise increase in the MTVsum and TLGtotal. (p = 0.028 and 0.039, respectively), but not the SUVmax and avgSUVmean (p = 0.526 and 0.729, respectively).ConclusionIn conclusion, the volume-based parameters of 18F-FDG PET/CT correlate with immunohistochemical staining of Ki-67 in SCLC. Measurement of the MTVsum and TLGtotal by 18F-FDG PET/CT might be a simple, noninvasive, and useful method to determine the proliferative potential of cancer cells.

Predictive Role of Functional Visceral Fat Activity Assessed by Preoperative F-18 FDG PET/CT for Regional Lymph Node or Distant Metastasis in Patients with Colorectal Cancer

Objectives To investigate the role of functional visceral fat activity assessed by preoperative F-18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in colorectal cancer (CRC) for predicting regional lymph node (LN) or distant metastasis. Method We evaluated 131 patients with newly diagnosed CRC. They all underwent pre-operative 18F-FDG PET/CT and surgery. Functional fat activity was measured by maximum standardized uptake value (SUVmax) using 18F-FDG PET/CT. Functional visceral fat activity was measured by SUVmax of visceral fat/SUVmax of subcutaneous fat (V/S) ratio. Mann-Whitney U test, χ2 test, Fisher’s exact test, receiver-operating characteristic (ROC) analysis, Spearrman’s correlation coefficient, and uni- and multivariate logistic regression statistical analyses were done. Results Patients with higher V/S ratio displayed a significantly higher rate of regional LN (p = 0.004) and distant metastasis (p<0.001). In addition, V/S ratio was the only factor that was significantly associated with distant metastasis. An optimal cut-off V/S ratio of 1.88 was proposed for predicting distant metastasis with a sensitivity of 84.6% and specificity of 78.8% (area under the curve: 0.86; p<0.0001) Conclusion Functional visceral fat activity is significantly associated with distant metastasis in CRC patients. Furthermore, V/S ratio can be useful as a complementary factor in predicting distant metastasis.

Early prediction of pathological complete response in luminal B type neoadjuvant chemotherapy-treated breast cancer patients: comparison between interim 18F-FDG PET/CT and MRI.

PurposeThe aim of this study is to justify the effectiveness of interim PET/computed tomography (CT) for predicting pathological complete response (pCR) in luminal B type breast cancer patients and to compare the diagnostic performance of interim PET/CT and MRI. Materials and methodsTwenty-one patients with neoadjuvant chemotherapy (NAC)-treated luminal B type breast cancer were included. All patients underwent PET/CT and MRI at baseline and interim (mid-point). Breast surgery was performed after completion of NAC. Maximum standardized uptake values (SUVmax) of breast malignant lesions in each PET/CT scan were acquired in each patient. The metabolic response was calculated as follows: &Dgr;SUV (%)=(baseline SUVmax−interim SUVmax)/baseline SUVmax×100 (%). In MRI, the relative size change was calculated as follows: Size change (%)=longest diameter interim MRI−longest diameter baseline MRI/longest diameter baseline MRI×100 (%). pCR was concluded through the final pathologic specimen after breast surgery. The receiver-operating characteristic analysis was used as a statistical method. ResultsOf 21 patients, seven achieved a pCR after surgery. In PET/CT, an optimal cut-off &Dgr;SUV (%) of 69.0% was proposed with a sensitivity of 85.7% and a specificity of 100% (P<0.0001). In MRI, an optimal cut-off size change (%) was 38.2% with a sensitivity of 64.3% and a specificity of 71.4% (P=0.29). The area under the curve was 0.92 and 0.65, respectively. PET/CT presented better predictability of the pCR than MRI (P=0.04). ConclusionIn luminal B type NAC-treated breast cancer patients, it is possible to use PET/CT as an early surrogate marker for predicting pCR and it is significantly more predictable for pCR than MRI.

Simvastatin Reduces Lipopolysaccharides-Accelerated Cerebral Ischemic Injury via Inhibition of Nuclear Factor-kappa B Activity

Preceding infection or inflammation such as bacterial meningitis has been associated with poor outcomes after stroke. Previously, we reported that intracorpus callosum microinjection of lipopolysaccharides (LPS) strongly accelerated the ischemia/reperfusion-evoked brain tissue damage via recruiting inflammatory cells into the ischemic lesion. Simvastatin, 3-hydroxy-3-methylgultaryl (HMG)-CoA reductase inhibitor, has been shown to reduce inflammatory responses in vascular diseases. Thus, we investigated whether simvastatin could reduce the LPS-accelerated ischemic injury. Simvastatin (20 mg/kg) was orally administered to rats prior to cerebral ischemic insults (4 times at 72, 48, 25, and 1-h pre-ischemia). LPS was microinjected into rat corpus callosum 1 day before the ischemic injury. Treatment of simvastatin reduced the LPS-accelerated infarct size by 73%, and decreased the ischemia/reperfusion-induced expressions of pro-inflammatory mediators such as iNOS, COX-2 and IL-1β in LPS-injected rat brains. However, simvastatin did not reduce the infiltration of microglial/macrophageal cells into the LPS-pretreated brain lesion. In vitro migration assay also showed that simvastatin did not inhibit the monocyte chemoattractant protein-1-evoked migration of microglial/macrophageal cells. Instead, simvastatin inhibited the nuclear translocation of NF-κB, a key signaling event in expressions of various proinflammatory mediators, by decreasing the degradation of IκB. The present results indicate that simvastatin may be beneficial particularly to the accelerated cerebral ischemic injury under inflammatory or infectious conditions.

Non-Selective Cannabinoid Receptor Antagonists, Hinokiresinols Reduce Infiltration of Microglia/Macrophages into Ischemic Brain Lesions in Rat via Modulating 2-Arachidonolyglycerol-Induced Migration and Mitochondrial Activity.

Growing evidence suggests that therapeutic strategies to modulate the post-ischemic inflammatory responses are promising approaches to improve stroke outcome. Although the endocannabinoid system has been emerged as an endogenous therapeutic target to regulate inflammation after stroke insult, the downstream mechanisms and their potentials for therapeutic intervention remain controversial. Here we identified trans- and cis-hinokiresinols as novel non-selective antagonists for two G-protein-coupled cannabinoid receptors, cannabinoid receptor type 1 and type 2. The Electric Cell-substrate Impedance Sensing and Boyden chamber migration assays using primary microglial cultures revealed that both hinokiresinols significantly inhibited an endocannabinoid, 2-arachidonoylglycerol-induced migration. Hinokiresinols modulated 2-arachidonoylglycerol-induced mitochondrial bioenergetics in microglia as evidenced by inhibition of ATP turnover and reduction in respiratory capacity, thereby resulting in impaired migration activity. In rats subjected to transient middle cerebral artery occlusion (1.5-h) followed by 24-h reperfusion, post-ischemic treatment with hinokiresinols (2 and 7-h after the onset of ischemia, 10 mg/kg) significantly reduced cerebral infarct and infiltration of ED1-positive microglial/macrophage cells into cerebral ischemic lesions in vivo. Co-administration of exogenous 2-AG (1 mg/kg, i.v., single dose at 2 h after starting MCAO) abolished the protective effect of trans-hinokiresionol. These results suggest that hinokiresinols may serve as stroke treatment by targeting the endocannabinoid system. Alteration of mitochondrial bioenergetics and consequent inhibition of inflammatory cells migration may be a novel mechanism underlying anti-ischemic effects conferred by cannabinoid receptor antagonists.

Peripheral bone involvement of intravascular large B-cell lymphoma on 99mTc-MDP bone scan and 18F-FDG PET/CT.

A 64-year-old man was admitted for evaluation of recently developed anemia and bone pain. The bone scan showed diffusely active lesions in the peripheral bones, symmetrically. Interestingly, 18F-FDG PET/CT revealed the hypermetabolic changes in the peripheral bones as well as the internal organs. Biopsy of bone marrow confirmed the diagnosis of intravascular B-cell lymphoma. After the 3 cycles of R-CHOP chemotherapy, 18F-FDG PET/CT showed improvement of the previous hypermetabolic lesions, suggesting good response. Intravascular B-cell lymphoma is a rare and aggressive variant of diffuse large cell lymphoma characterized by proliferation of malignant cells within the vascular lumina.

Visualization of Synthetic Vascular Smooth Muscle Cells in Atherosclerotic Carotid Rat Arteries by F-18 FDG PET.

Synthetic vascular smooth muscle cells (VSMCs) play important roles in atherosclerosis, in-stent restenosis, and transplant vasculopathy. We investigated the synthetic activity of VSMCs in the atherosclerotic carotid artery using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). Atherosclerosis was induced in rats by partial ligation of the right carotid artery coupled with an atherogenic diet and vitamin D injections (2 consecutive days, 600,000 IU/day). One month later, rats were imaged by F-18 FDG PET. The atherosclerotic right carotid arteries showed prominent luminal narrowing with neointimal hyperplasia. The regions with neointimal hyperplasia were composed of α-smooth muscle actin-positive cells with decreased expression of smooth muscle myosin heavy chain. Surrogate markers of synthetic VSMCs such as collagen type III, cyclophilin A, and matrix metallopeptidase-9 were increased in neointima region. However, neither macrophages nor neutrophils were observed in regions with neointimal hyperplasia. F-18 FDG PET imaging and autoradiography showed elevated FDG uptake into the atherosclerotic carotid artery. The inner vessel layer showed higher tracer uptake than the outer layer. Consistently, the expression of glucose transporter 1 was highly increased in neointima. The present results indicate that F-18 FDG PET may be a useful tool for evaluating synthetic activities of VSMCs in vascular remodeling disorders.

Is it Feasible to Use the Commercially Available Autoquantitation Software for the Evaluation of Myocardial Viability on Small-Animal Cardiac F-18 FDG PET Scan?

PurposeTo evaluate the reliability of quantitation of myocardial viability on cardiac F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) scans with three different methods of visual scoring system, autoquantitation using commercially available autoquantitation software, and infarct-size measurement using histogram-based maximum pixel threshold identification on polar-map in rat hearts.MethodsA myocardial infarct (MI) model was made by left anterior descending artery (LAD) ligation in rat hearts. Eighteen MI rats underwent cardiac FDG-PET-computed tomography (CT) twice within a 4-week interval. Myocardium was partitioned into 20 segments for the comparison, and then we quantitated non-viable myocardium on cardiac FDG PET-CT with three different methods: method A—infarct-size measurement using histogram-based maximum pixel threshold identification on polar-map; method B—summed MI score (SMS) by a four-point visual scoring system; method C—metabolic non-viable values by commercially available autoquantitation software. Changes of non-viable myocardium on serial PET-CT scans with three different methods were calculated by the change of each parameter. Correlation and reproducibility were evaluated between the different methods.ResultsInfarct-size measurement, visual SMS, and non-viable values by autoquantitation software presented proportional relationship to each other. All the parameters of methods A, B, and C showed relatively good correlation between each other. Among them, infarct-size measurement (method A) and autoquantitation software (method C) showed the best correlation (r = 0.87, p < 0.001). When we evaluated the changes of non-viable myocardium on the serial FDG-PET-CT- however, autoquantitation program showed less correlation with the other methods. Visual assessment (method B) and those of infarct size (method A) showed the best correlation (r = 0.54, p = 0.02) for the assessment of interval changes.ConclusionsCommercially available quantitation software could be applied to measure the myocardial viability on small animal cardiac FDG-PET-CT scan. This kind of quantitation showed good correlation with infarct size measurement by histogram-based maximum pixel threshold identification. However, this method showed the weak correlation when applied in the measuring the changes of non-viable myocardium on the serial scans, which means that the caution will be needed to evaluate the changes on the serial monitoring.

Predictive value of dual-time 18F-FDG PET/CT to distinguish primary lung and metastatic adenocarcinoma in solitary pulmonary nodule

Aims and background: Distinction between primary lung adenocarcinoma and metastatic adenocarcinoma from extrapulmonary origin in solitary pulmonary nodule (SPN) is crucial for cancer treatment. We investigated the predictive role of dual-time-point 18F-FDG PET/CT to distinguish primary and metastatic lung adenocarcinoma in SPN. Methods: A total of 96 consecutive patients with newly diagnosed SPN and biopsy-proven adenocarcinoma were enrolled in this study, retrospectively (54 male; 42 female; age 59.68 ± 8.2 years). They all underwent dual-time-point 18F-FDG PET/CT at 60 minutes (early) for whole body and 120 minutes (delayed) for chest region after FDG injection. Maximum standardized uptake values (early SUVmax and delayed SUVmax) and retention index (RI) were acquired for analysis. Final pathology results were confirmed by surgical specimens. Results: Metastatic adenocarcinoma showed significantly higher early SUVmax, delayed SUVmax, and RI compared to primary lung adenocarcinoma. Delayed SUVmax and RI presented superior diagnostic performance for prediction of metastatic adenocarcinoma than early 18F-FDG PET/CT. Among metastatic adenocarcinoma, metastasis from colorectal origin showed significantly higher RI than from other origins. In addition, RI significantly predicted metastatic adenocarcinoma from colorectal cancer than early or delayed SUVmax. Conclusions: Dual-timepoint 18F-FDG PET/CT can be useful to distinguish primary and metastatic lung adenocarcinoma in SPN. Furthermore, it may also be useful to predict metastatic adenocarcinoma from colorectal origin.

Metabolic tumor heterogeneity analysis by F-18 FDG PET/CT predicts mediastinal lymph node metastasis in non-small cell lung cancer patients with clinically suspected N2

OBJECTIVES Accurate prediction of pathological N2 metastasis is crucial for choosing the best therapeutic strategy for non-small cell lung cancer (NSCLC) patients. The aim of this study is to evaluate the usefulness of metabolic heterogeneity assessed by the positron emission tomography combined with computed tomography (PET/CT) using F-18 fluorodeoxyglucose (FDG) in primary NSCLC with clinically suspected N2 metastasis in predicting pathological mediastinal lymph node metastasis. MATERIALS AND METHODS Fifty patients with newly diagnosed NSCLC and clinically suspected N2 on preoperative CT and F-18 FDG PET/CT were included. Pathological results were confirmed by surgical specimens and the coefficient of variation (COV) was used to evaluate the metabolic heterogeneity of primary tumor mass by using F-18 FDG PET/CT. RESULTS Among the 50 patients with clinically suspected N2, 23 patients were pathologically confirmed as positive mediastinal lymph node metastasis and 27 patients were negative. Pathologically confirmed positive mediastinal lymph node metastasis group presented higher COV than the negative metastasis group (p < 0.001). An optimal cut-off value of 41.9 was proposed for discriminating metastasis from non-metastasis group. The sensitivity and specificity were 65.2% and 88.9%, respectively (AUC: 0.84; p < 0.0001). In addition, compared with other metabolic parameters, metabolic heterogeneity defined as COV showed the superior predictability of the mediastinal metastasis. (p = 0.001) CONCLUSION: Metabolic heterogeneity which was defined as COV of primary tumor could predict pathological mediastinal lymph node metastasis in NSCLC patients with clinically suspected N2. Therefore, COV of primary tumor may play a complementary role to conventional imaging in providing nodal information before taking biopsy.