Phase I Clinical Trial of Prostate-Specific Membrane Antigen-Targeting 68 Ga-NGUL PET/CT in Healthy Volunteers and Patients with Prostate Cancer

Objective@#68 Ga-NGUL is a novel prostate-specific membrane antigen (PSMA)-targeting tracer based on Glu-Urea-Lys derivatives conjugated to a 1,4,7-triazacyclononane-N,N’,N’’-triacetic acid (NOTA) chelator via a thiourea-type short linker. This phase I clinical trial of 68 Ga-NGUL was conducted to evaluate the safety and radiation dosimetry of 68 Ga-NGUL in healthy volunteers and the lesion detection rate of 68 Ga-NGUL in patients with prostate cancer. @*Materials and Methods@#We designed a prospective, open-label, single-arm clinical trial with two cohorts comprising six healthy adult men and six patients with metastatic prostate cancer. Safety and blood test-based toxicities were monitored throughout the study. PET/CT scans were acquired at multiple time points after administering 68 Ga-NGUL (2 MBq/kg; 96–165 MBq). In healthy adults, absorbed organ doses and effective doses were calculated using the OLINDA/EXM software. In patients with prostate cancer, the rates of detecting suspicious lesions by 68 Ga-NGUL PET/CT and conventional imaging (CT and bone scintigraphy) during the screening period, within one month after recruitment, were compared. @*Results@#All 12 participants (six healthy adults aged 31–32 years and six prostate cancer patients aged 57–81 years) completed the clinical trial. No drug-related adverse events were observed. In the healthy adult group, 68 Ga-NGUL was rapidly distributed, with the highest uptake in the kidneys. The median effective dose coefficient was calculated as 0.025 mSv/MBq, and cumulative activity in the bladder had the highest contribution. In patients with metastatic prostate cancer, 229 suspicious lesions were detected using either 68 Ga-NGUL PET/CT or conventional imaging. Among them, 68 Ga-NGUL PET/CT detected 199 (86.9%) lesions and CT or bone scintigraphy detected 114 (49.8%) lesions. @*Conclusion@#68 Ga-NGUL can be safely applied clinically and has shown a higher detection rate for the localization of metastatic lesions in prostate cancer than conventional imaging. Therefore, 68 Ga-NGUL is a valuable option for prostate cancer imaging.

Association between Education Level and Diabetes in Korean Adults Over 30 Years Old: The Seventh Korea National Health and Nutrition Examination Survey (2016–2017)

Background@#It has been reported that low education levels are associated with an increased prevalence of diabetes mellitus. The aim of this study was to investigate the relationship between education level and the prevalence of diabetes. @*Methods@#This study was based on the original data of the 7th Korea National Health and Nutrition Examination Survey (2016–2017). In total, 4,819 adults over 30 years of age participated in this study, and multiple logistic regression analysis was used to derive the odds ratio and 95% confidence interval to assess the relationship between education level and diabetes. The influence of sex, age, obesity, depression, drinking, smoking, and occupation was analyzed to determine the net influence of education level on the prevalence of diabetes mellitus. @*Results@#The level of education and prevalence of diabetes were significantly correlated. When the level of education was high, the possibility of diabetes mellitus was higher than that in university graduates (odds ratios=1.836, P<0.05); however, the prevalence of diabetes mellitus was not significantly different from that in college graduates. The effect of correction variables on the prevalence of diabetes showed significant differences (P<0.05) in sex, age, obesity, and occupation. @*Conclusion@#There was a statistically significant association between the low level of education and the prevalence of diabetes mellitus in this study; therefore, active intervention for diabetes is required in people with low education.

Nonmotor and Dopamine Transporter Change in REM Sleep Behavior Disorder by Olfactory Impairment

OBJECTIVE: It is unclear whether the decline in dopamine transporters (DAT) differs among idiopathic rapid eye movement sleep behavior disorder (iRBD) patients with different levels of olfactory impairment. This study aimed to characterize DAT changes in relation to nonmotor features in iRBD patients by olfactory loss. METHODS: This prospective cohort study consisted of three age-matched groups: 30 polysomnography-confirmed iRBD patients, 30 drug-naïve Parkinson's disease patients, and 19 healthy controls without olfactory impairment. The iRBD group was divided into two groups based on olfactory testing results. Participants were evaluated for reported prodromal markers and then underwent 18F-FP-CIT positron emission tomography and 3T MRI. Tracer uptakes were analyzed in the caudate, anterior and posterior putamen, substantia nigra, and raphe nuclei. RESULTS: Olfactory impairment was defined in 38.5% of iRBD patients. Mild parkinsonian signs and cognitive functions were not different between the two iRBD subgroups; however, additional prodromal features, constipation, and urinary and sexual dysfunctions were found in iRBD patients with olfactory impairment but not in those without. Tracer uptake showed significant group differences in all brain regions, except the raphe nuclei. The iRBD patients with olfactory impairment had uptake reductions in the anterior and posterior putamen, caudate, and substantia nigra (p < 0.016 in all, adjusted for age), which ranged from 0.6 to 0.8 of age-normative values. In contrast, those without olfactory impairment had insignificant changes in all regions ranging above 0.8. CONCLUSION: There was a clear distinction in DAT loss and nonmotor profiles by olfactory status in iRBD.

Comparison of Risk Factors for Type 2 Diabetes Mellitus in One-Person Households and Multi-Person Households

BACKGROUND: Recently, the number of one-person households has increased, and the prevalence of type 2 diabetes mellitus has risen in Korea. Major complications of diabetes, such as stroke and myocardial infarction are major causes of death. Therefore, we conducted this study to test the hypothesis that the risk factors and prevalence of type 2 diabetes mellitus differ between one-person and multi-person households.METHODS: This retrospective study analyzed data of 3,691 adults over 19 years old from the 7th (2016) Korea National Health and Nutrition Examination Survey. Data were analyzed by composite sampling for age, family history, waist circumference, body mass index, hypertension, high-density lipoprotein cholesterol, triglycerides, smoking, alcohol consumption, physical activity, and consumption of breakfast. Multivariate logistic regression analysis was performed by household-type in order to estimate the relative risk of factors associated with diabetes.RESULTS: Hypertension was a significant risk factor for diabetes in both groups. Among other diabetic risk factors, individuals in one-person households were more likely to skip breakfast and less likely to engage in physical activity than those in multi-person households.CONCLUSION: One-person households have a high risk of hypertension, skipping breakfast, and poor physical activity. It is important to consider the role of one-person households when studying the management and treatment of disease.

Intracellular Ca2+ Mobilization and Beta-hexosaminidase Release Are Not Influenced by 60 Hz-electromagnetic Fields (EMF) in RBL 2H3 Cells

The effects of extremely low frequency electromagnetic fields (EMF) on intracellular Ca2+ mobilization and cellular function in RBL 2H3 cells were investigated. Exposure to EMF (60 Hz, 0.1 or 1 mT) for 4 or 16 h did not produce any cytotoxic effects in RBL 2H3 cells. Melittin, ionomycin and thapsigargin each dose-dependently increased the intracellular Ca2+ concentration. The increase of intracellular Ca2+ induced by these three agents was not affected by exposure to EMF (60 Hz, 1 mT) for 4 or 16 h in RBL 2H3 cells. To investigate the effect of EMF on exocytosis, we measured beta-hexosaminidase release in RBL 2H3 cells. Basal release of beta-hexosaminidase was 12.3+/-2.3% in RBL 2H3 cells. Exposure to EMF (60 Hz, 0.1 or 1 mT) for 4 or 16 h did not affect the basal or 1 microM melittin-induced beta-hexosaminidase release in RBL 2H3 cells. This study suggests that exposure to EMF (60 Hz, 0.1 or 1 mT), which is the limit of occupational exposure, has no influence on intracellular Ca2+ mobilization and cellular function in RBL 2H3 cells.

Small Animal PET Imaging Study of 68Ga-BAPEN / 의학물리

The purpose of this study was to analyze 68Ga-BAPEN dynamic PET image in rat myocardium to evaluate potential of this radiotracer as a perfusion imaging agent. Animal PET/CT scan was done in 9 rats during 120 minutes. Especially we synthesized 68Ga-BAPEN with kit which is simple and low cost method. PET images showed the in vivo dynamic distribution of 68Ga-BAPEN in the chest region of rats. Initially 68Ga-BAPEN PET images showed aorta and liver activities and a few minutes later, 68Ga-BAPEN moved to myocardium. Regions of interest were drawn on myocardium, liver, lung and blood pool. Time-activity curves showed significant uptake of 68Ga-BAPEN in myocardium. The contrast ratios of myocardial to blood pool, lung and liver at 60 minutes after injection were 1.66, 2.82 and 0.60. To estimate accurate kinetic parameters, 60 minutes after injection was required to PET scan as myocardium image contrast ratios reached to constant values. As a result, 68Ga-BAPEN would be suitable radiotracer for PET which can applied to diagnosis of myocardial perfusion diseases after further preclinical and clinical investigations.

Effect of Extremely Low Frequency Electromagnetic Fields (EMF) on Phospholipase Activity in the Cultured Cells

This study was conducted to investigate the effects of extremely low frequency electromagnetic fields (EMF) on signal pathway in plasma membrane of cultured cells (RAW 264.7 cells and RBL 2H3 cells), by measuring the activity of phospholipase A2 (PLA2), phospholipase C (PLC) and phospholipase D (PLD). The cells were exposed to the EMF (60 Hz, 0.1 or 1 mT) for 4 or 16 h. The basal and 0.5 microM melittin-induced arachidonic acid release was not affected by EMF in both cells. In cell-free PLA2 assay, we failed to observe the change of cPLA2 and sPLA2 activity. Also both PLC and PLD activities did not show any change in the two cell lines exposed to EMF. This study suggests that the exposure condition of EMF (60 Hz, 0.1 or 1 mT) which is 2.4 fold higher than the limit of occupational exposure does not induce phospholipases-associated signal pathway in RAW 264.7 cells and RBL 2H3 cells.

Morinda citrifolia Inhibits Both Cytosolic Ca2+-dependent Phospholipase A2 and Secretory Ca2+-dependent Phospholipase A2

This study investigated the effects of the methanol extracts of Morinda citrifolia containing numerous anthraquinone and iridoid on phospholipase A2 (PLA2) isozyme. PLA2 activity was measured using various PLA2 substrates, including 10-pyrene phosphatidylcholine, 1-palmitoyl-2-[14C]arachidonyl phosphatidylcholine ([14C]AA-PC), and [3H]arachidonic acid (AA). The methanol extracts suppressed melittin-induced [3H]AA release in a concentration-dependent manner in RAW 264.7 cells, and inhibited cPLA2/sPLA2-induced hydrolysis of [14C]AA-PC in a concentration- and time-dependent manner. A Dixon plot showed that the inhibition by methanol extracts on cPLA2 and sPLA2 appeared to be competitive with inhibition constants (Ki ) of 3.7microgram/ml and 12.6microgram/ml, respectively. These data suggest that methanol extracts of Morinda citrifolia inhibits both Ca2+-dependent PLA2 such as, cPLA2 and sPLA2. Therefore, Morinda citrifolia may possess anti-inflammatory activity secondary to Ca2+-dependent PLA2 inhibition.

Radiolabeling of NOTA and DOTA with Positron Emitting 68Ga and Investigation of In Vitro Properties / 핵의학분자영상

PURPOSE: We established radiolabeling conditions of NOTA and DOTA with a generator-produced PET radionuclide 68Ga and studied in vitro characteristics such as stability, serum protein binding, octanol/water distribution, and interference with other metal ions. MATERIALS AND METHODS: Various concentrations of NOTA.3HCl and DOTA.4HCl were labeled with 1 mL 68GaCl3 (0.18~5.75 mCi in 0.1 M HCl) in various pH. NOTA.3HCl (0.373 mM) was labeled with 68GaCl3 (0.183~0.232 mCi/0.1 M HCl 1.0 mL) in the presense of CuCl2, FeCl2, InCl3, FeCl3, GaCl3, MgCl2 or CaCl2 (0~6.07 mM) at room temperature. The labeling efficiencies of 68Ga-NOTA and 68Ga-DOTA were checked by ITLC-SG using acetone or saline as mobile phase. Stabilities, protein bindings, and octanol distribution coefficients of the labeled compounds also were investigated. RESULTS: 68Ga-NOTA and 68Ga-DOTA were labeled optimally at pH 6.5 and pH 3.5, respectively, and the chelates were stable for 4 hr either in the reaction mixture at room temperature or in the human serum at 37 degreesC. NOTA was labeled at room temperature while DOTA required heating for labeling. 68Ga-NOTA labeling efficiency was reduced by CuCl2, FeCl2, InCl2, FeCl3 or GaCl3, however, was not influenced by MgCl2 or CaCl2. The protein binding was low (2.04~3.32%). Log P value of 68Ga-NOTA was -3.07 indicating high hydrophilicity. CONCLUSION: We found that NOTA is a better bifunctional chelating agent than DOTA for 68Ga labeling. Although, 68Ga-NOTA labeling is interfered by various metal ions, it shows high stability and low serum protein binding.

A Convenient Radiolabeling of 11C(R)-PK11195 Using Loop Method in Automatic Synthesis Module / 핵의학분자영상

PURPOSE: ((R)-1-(2-chlorophenyl)-N-1-[11C]methyl-N-(1-propyl)-3-isoquinoline carboxamide ((R)-PK11195) is a specific ligand for the peripheral type benzodiazepine receptor and a marker of activated microglia, used to measure inflammation in neurologic disorders. We report here that a direct and simple radiosynthesis of [11C](R)-PK11195 inmild condition using NaH suspension in DMF and one-step loop method. MATERIALS AND METHODS: (R)-NDesmethyl- PK11195 (1 mg) in DMSO (0.1 mL) and NaH suspension in DMF (0.1 mL) were injected into a semi-prep HPLC loop. [11C]methyl iodide was passed through HPLC loop at room temperature. Purification was performed using semi-preparative HPLC. Aliquots eluted at 11.3 min were collected and analyzed by analytical HPLC and mass spectrometer. RESULTS: The labeling efficiency of [11C](R)-PK11195 was 71.8+/-8.5%. The specific activity was 11.8 +/-6.4 GBq/micromol and radiochemical purity was higher than 99.2%. The mass spectrum of the product eluted at 11.3 min showed m/z peaks at 353.1 (M+1), indicating the mass and structure of (R)-PK11195. CONCLUSION: By the one-step loop method with the [11C]CH3I automated synthesis module, [11C](R)-PK11195 could be easily prepared in high radiochemical yield using NaH suspension in DMF.

Optimization of Inpatient Management of Radioiodine Treatment in Korea / 핵의학분자영상

We established a model to calculate radioactive waste from sewage disposal tank of hospitals to optimize the number of patients receiving inpatient radioiodine therapy within the safety guideline in our country. According to this model and calculation of radioactivity concentration using the number of patients per week, the treatment dose of radioiodine, the capacity and the number of sewage tanks and the daily amount of water waste per patient, estimated concentration of radioactivity in sewage waste upon disposal from disposal tanks after longterm retention were within the safety guideline (30 Bq/L) in all the hospitals examined. In addition to the fact that we could increase the number of patients in two thirds of hospitals, we found that the daily amount of waste water was the most important variable to allow the increase of the number of patients within the safety margin of disposed radioactivity. We propose that saving the water amount be led to increase the number of patients and they allow two patients in an already furnished hospital inpatient room to meet the increasing need of inpatient radioiodine treatment for thyroid cancer.

Radiosynthesis of 11C6-OH-BTA-1 in Different Media and Confirmation of Reaction By-products / 핵의학분자영상

PURPOSE: [11C]6-OH-BTA-1 ([N-methyl-11C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole, 1), a -amyloid imaging agent for the diagnosis of Alzheimer's disease in PET, can be labeled with higher yield by a simple loop method. During the synthesis of [11C]1, we found the formation of by-products in various solvents, e.g., methylethylketone (MEK), cyclohexanone (CHO), diethylketone (DEK), and dimethylformamide (DMF). MATERIALS AND METHODS: In Automated radiosynthesis module, 1 mg of 4-aminophenyl-6-hydroxybenzothiazole (4) in 100 l of each solvent was reacted with [11C]methyl triflate in HPLC loop at room temperature (RT). The reaction mixture was separated by semi-preparative HPLC. Aliquots eluted at 14.4, 16.3 and 17.6 min were collected and analyzed by analytical HPLC and LC/MS spectrometer. RESULTS: The labeling efficiencies of [11C]1 were 86.0+/-5.5%, 59.7+/-2.4%, 29.9+/-1.8%, and 7.6+/-0.5% in MEK, CHO, DEK and DMF, respectively. The LC/MS spectra of three products eluted at 14.4, 16.3 and 17.6 mins showed m/z peaks at 257.3 (M+1), 257.3 (M+1) and 271.3 (M+1), respectively, indicating their structures as 1, 2-(4'-aminophenyl)-6-methoxybenzothiazole (2) and by-product (3), respectively. Ratios of labeling efficiencies for the three products ([11C]1:[11C]2:[11C]3) were 86.0+/-5.5%:5.0+/-3.4%:1.5+/-1.3% in MEK, 59.7+/-2.4%:4.7+/-3.2%:1.3+/-0.5% in CHO, 9.9+/-1.8%:2.0+/-0.7%:0.3+/-0.1% in DEK and 7.6+/-0.5%:0.0%:0.0% in DMF, respectively. CONCLUSION: The labeling efficiency of [11C]1 was the highest when MEK was used as a reaction solvent. As results of mass spectrometry, 1 and 2 were conformed. 3 was presumed.

beta-Amyloid Imaging Probes / 핵의학분자영상

Imaging distribution of beta-amyloid plaques in Alzheimer's disease is very important for early and accurate diagnosis. Early trial of the beta-amyloid plaques includes using radiolabeled peptides which can be only applied for peripheral beta-amyloid plaques due to limited penetration through the blood brain barrier (BBB). Congo red or Chrysamine G derivatives were labeled with Tc-99m for imaging beta-amyloid plaques of Alzheimer patient's brain without success due to problem with BBB penetration. Thioflavin T derivatives gave breakthrough for beta-amyloid imaging in vivo, and a benzothiazole derivative [C-11]6-OH-BTA-1 brought a great success. Many other benzothiazole, benzoxazole, benzofuran, imidazopyridine, and styrylbenzene derivatives have been labeled with F-18 and I-123 to improve the imaging quality. However, [C-11]6-OH-BTA-1 still remains as the best. However, short half-life of C-11 is a limitation of wide distribution of this agent. So, it is still required to develop an Tc-99m, F-18 or I-123 labeled agent for beta-amyloid imaging agent.

Quality Control of Residual Solvents in 18FFDG Preparations by Gas Chromatography / 핵의학분자영상

PURPOSE: Analysis of volatile organic solvents in 2-deoxy-2-[18F] fluoro-D-glucose ([18F]FDG) preparations was performed by gas chromatography (GC), in accordance with USP. MATERIALS AND METHODS: Analyses were carried out on a Hewlett-Packard 6890 gas chromatography equipped with an FID. RESULTS: We determined the amounts of ethanol and acetonitrile on every batch of our routine [18F]FDG preparations, ranging between 5000 ppm and 100 ppm. In our routine preparation of [18F]FDG, the amount of acetonitrile and ethanol in the final product were well below the maximum allowable limit described in the USP. CONCLUSION: Our [18F]FDG preparations were in accordance with the suggested USP maximum allowable levels of the quality control analysis of volatile organic compounds.

Regulatory Problems in Radionuclide Therapy and Suggestions for Systematic Improvement / 핵의학분자영상

Radionuclide therapy has been used for more than 50 years and proved to be a safe and effective modality. However, the patients' right to have the excellent medical service is seriously disturbed by excessive regulations of government institutions such as Korea Institute of Nuclear Safety (KINS), Health Insurance Review Agency (HIRA) and Korea Food and Drug Administration (KFDA). For example, the patients should wait for more than 6 months to have I-131 treatment in many hospitals. It is strongly recommended to mitigate the regulations to resonable levels to solve the problems. If HIRA allow the hospitals to charge reasonable rate for radionuclide therapy room, then more hospitals would invest to build the radionuclide therapy rooms and the patients' waiting time would decrease. The waiting time would also decrease, if KINS allow 2 patients to share a radionuclide therapy room. Finally, it is strongly recommended to lower the threshold for approval of new therapeutic radiopharmaceuticals by KFDA, which would allow new effective therapeutic radiopharmaceuticals to be introduced to clinical practices more easily.

Smoking-Induced Dopamine Release Studied with 11CRaclopride PET / 대한핵의학회잡지

PURPOSE: It has been postulated that dopamine release in the striatum underlies the reinforcing properties of nicotine. Substantial evidence in the animal studies demonstrates that nicotine interacts with dopaminergic neuron and regulates the activation of the dopaminergic system. The aim of this study was to visualize the dopamine release by smoking in human brain using PET scan with [11C]raclopride. MATERIALS AND METHODS: Five male non-smokers or ex-smokers with an abstinence period longer than 1 year (mean age of 24.4+/-1.7 years) were enrolled in this study. [11C]raclopride, a dopamine D2 receptor radioligand, was administrated with bolus-plus- constant infusion. Dynamic PET was performed during 120 minutes (3x20s, 2x60s, 2x120s, 1x180s and 22x300s). Following the 50 minute-scanning, subjects smoked a cigarette containing 1 mg of nicotine while in the scanner. Blood samples for the measurement of plasma nicotine level were collected at 0, 5, 10, 15, 20, 25, 30, 45, 60, and 90 minute after smoking. Regions for striatal structures were drawn on the coronal summed PET images guided with co-registered MRI. Binding potential, calculated as (striatal-cerebellar) /cerebellar activity, was measured under equilibrium condition at baseline and smoking session. RESULTS: The mean decrease in binding potential of [11C]raclopride between the baseline and smoking in caudate head, anterior putamen and ventral striatum was 4.7 %, 4.0 % and 7.8 %, respectively. This indicated the striatal dopamine release by smoking. Of these, the reduction in binding potential in the ventral striatum was significantly correlated with the cumulated plasma level of the nicotine (Spearman's rho=0.9, p=0.04). CONCLUSION: These data demonstrate that in vivo imaging with [11C]raclopride PET could measure nicotine-induced dopamine release in the human brain, which has a significant positive correlation with the amount of nicotine administered by smoking.

Biodistribution of (99m) Tc-Lactosylated Serum Albumin in Mice with Diethylnitrosamine or Thiacetamide Induced Liver Injury / 대한핵의학회잡지

PURPOSE: Tc-99m labeled diethylenetriaminepentaacetic acid (DTPA) -coupled galactosylated human serum albumin (GSA) is a currently used imaging agent for asialoglycoprotein receptor (ASGPR) of the liver, but, it has several shortcomings. Recently a new ASGPR imaging agent, (99m) Tc-lactosylated human serum albumin (LSA), with simple labeling procedure, high labeling efficiency, high stability was developed. In order to assess the feasibility of the (99m) Tc-LSA as a ASGPR imaging radiopharmaceuticals, we performed biodistribution study of the tracer in liver injured mice model and the results were compared with histolgic data. MATERIALS AND METHODS: To induce hepatic damage in ICR mice, diethylnitrosamine (DEN) (60 mg/kg/week X 5 time, low dose or 180 mg/kg/week X 2 times, high dose) and thioacetamide (TAA) (50 mg/kg X 1 time) were administrated intraperitoneally. Degree of liver damage was evaluated by tissue hematoxilin-eosin stain, and expression of asialoglycoprotein receptor (ASGPR) was assessed by immunohistochemistry using ASGPR antibody. (99m) Tc-LSA was intravenously administrated via tail vein in DEN or TAA treated mice, and biodistribution study of the tracer was also performed. RESULTS: DEN treated mice showed ballooning of hepatocyte and inflammatory cell infiltration in low dose group and severe hapatocyte necrosis in high dose group, and low dose group showed higher ASGPR staining than control mice in immunohistochemical staining. TAA treated mice showed severe hepatic necrosis. (99m) Tc-LSA Biodistribution study showed that mice with hepatic necrosis induced by high dose DEN or TAA revealed higher blood activity and lower liver activity than control mice, due to slow clearance of the tracer by the liver. The degree of liver uptake was inversely correlated with the degree of histologic liver damage. But low dose DEN treated mice with mild hepatic injury showed normal blood clearance and hepatic activity, partly due to overexpression of ASGPR in mice with mild degree hepatic injury. CONCLUSION: Liver uptake of (99m) Tc-LSA was inversely correlated with degree of histologic hepatic injury in DEN and TAA treated mice. These results support that (99m) Tc-LSA can be used to evaluate the liver status in liver disease patients.

Usefulness of Additional Delayed Regional F-18 Fluorodeoxyglucose Positron Emission Tomography in the Lymph Node Staging of Non-Small Cell Lung Cancer Patients / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: In this study, we examined whether additional, delayed regional FDG PET scans could increase the accuracy of the lymph node staging of NSCLC patients. MATERIALS AND METHODS: Among 87 patients who underwent open thoracotomy or mediastinoscopic biopsy under the suspicion of NSCLC, 35 (32 NSCLC and 3 infectious diseases) who had visible lymph nodes on both preoperative whole body scan and regional FDG PET scan were included. The following 3 calculations were made for each biopsy-proven, visible lymph node: maximum SUV of whole body scan (WB SUV), maximum SUV of delayed chest regional scan (Reg SUV), and the percent change of SUV between WB and regional scans (% SUV Change). ROC curve analyses were performed for WB SUVs, Reg SUVs and % SUV Changes. RESULTS: Seventy lymph nodes (29 benign, 41 malignant) were visible on both preoperative whole bodyscan and regional scan. The means of WB SUVs, Reg SUVs and % SUV Changes of the 41 malignant nodes, 3.71+/-1.08, 5.18+/-1.60, and 42.59+/-33.41%, respectively, were all significantly higher than those of the 29 benign nodes, 2.45+/-0.73, 3.00+/-0.89, and 22.71+/-20.17%, respectively. ROC curve analysis gave sensitivity and specificity values of 80.5% and 82.8% at a cutoff of 2.89 (AUC 0.839) for WB SUVs, 87.8% and 82.8% at a cutoff of 3.61 (AUC 0.891) for Reg SUVs, and 87.8% and 41.4% at a cutoff of 12.3% (AUC 0.671) for % SUV Changes. CONCLUSION: Additional, delayed regional FDG PET scans may improve the accuracy of lymph node staging of whole body FDG PET scan by providing additional criteria of Reg SUV and % SUV Change.

The Relationship between Expression of the Sodium/iodide Symporter Gene and the Status of Hormonal Receptors in Human Breast Cancer Tissue / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: It has been reported that the sodium/iodide symporter (NIS) gene is expressed in several breast cancer tissues, suggesting the possibility of radionuclide imaging and therapy. However, the regulatory mechanism of NIS gene expression in breast cancer is not yet understood. To assess the relationship between the hormonal status and the NIS expression in breast cancer tissue, we investigated the NIS expression and correlated it to the expression of the thyrotropin receptor (thyroid stimulating hormone receptor, TSH-R), the estrogen receptor (ER) and the progesterone receptor (PR) in human breast cancer tissues. MATERIALS AND METHODS: Breast cancer tissues were obtained from 44 patients. Pathological examination showed 2 cases of Grade I, 17 of Grade II, 22 of Grade III, and 3 of unknown grade. We measured the expression of NIS and TSH-R genes by using RT-PCR and we measured the status of ER and PR by using immunohisto-chemistry. RESULTS: The NIS gene was expressed in 15 (34%) of the 44 breast cancer tissues. The NIS gene was expressed in 32% of the cases with TSH-R gene expression. The NIS gene was expressed in 40% of the breast cancer tissues with a positive PR and in 31% with a negative PR (p>0.05). It was positive for PR in 18% of the cases and negative for PR in 39% of the cases (p>0.05). CONCLUSION: The NIS gene is expressed in approximately one-third of the human breast cancer tissues. Its expression was not related to the presence of the TSH-R gene or hormonal receptors, ER and PR.

Ethical and Regulatory Problems of Molecular Imaging / 대한핵의학회잡지

As a molecular imaging is the most up-to-date technology in Nuclear Medicine, it has complicate ethical and regulatory problems. For animal experiment, we have to follow institutional animal care committee. For clinical experiment, we have to get approval of Institutional Review Board according to Helsinki declaration. In addition, approval from Korea Food and Drug Administration (KFDA) is essential for manufacturing and commercialization. However, too much regulation would suppress development of new technology, which would result in the loss of national competitive power. In addition, most new radioactive ligands for molecular imaging are administered to human at sub-pharmacological and sub-toxicological level. In conclusion, a balanced regulation is essential for the safety of clinical application and development of new technology.