Diagnostic value of CT density in patients with diffusely increased FDG uptake in the thyroid gland on PET/CT images.

OBJECTIVE: The purpose of this article is to determine the diagnostic significance of thyroid density as determined by CT in patients with a diffuse hypermetabolic thyroid on PET/CT images. SUBJECTS AND METHODS: One hundred twelve patients were enrolled in this study, and all underwent PET/CT and a thyroid function test between August 2007 and December 2008. The 56 study patients enrolled had visible (18)F-FDG uptake in the thyroid, whereas the 56 control subjects had no visible FDG uptake. Maximum standardized uptake values (SUV(max)), Hounsfield units, thyroid-stimulating hormone levels, free thyroxine levels, and visual assessments of thyroid CT densities (grades 0-2) were evaluated. Analyses were performed to identify variables that differed between patients and control subjects and to examine relationships between Hounsfield unit and SUV(max) values, free thyroxine level, or thyroid-stimulating hormone level. RESULTS: Mean Hounsfield unit and SUV(max) values were significantly different between the two groups (p < 0.001), and SUV(max) values were found to be significantly different between grades. Free thyroxine and thyroid-stimulating hormone levels were also significantly different between thyroid density grades 0 and 2 (p < 0.001). A strongly negative relationship was found between Hounsfield units and SUV(max) values (r = 0.75), whereas Hounsfield units were found to be weakly correlated with free thyroxine level (r = 0.36) and thyroid-stimulating hormone level (r = -0.33). CONCLUSION: CT density is closely related to FDG uptake, and low CT density coupled with high FDG uptake suggests a change in thyroid tissue composition and is probably helpful for assessing the disease process and thyroid function of patients whose thyroid show diffuse FDG uptake on FDG PET/CT.

Effect of all-trans retinoic acid on sodium/iodide symporter expression, radioiodine uptake and gene expression profiles in a human anaplastic thyroid carcinoma cell line.

The plasma membrane glycoprotein sodium/iodide symporter (NIS) is crucial for thyroid hormone biosynthesis and mediates the iodide uptake of thyrocytes. It has been shown that retinoic acid (RA) alters NIS gene expression in thyroid carcinoma lines and stimulates their iodide uptake. Here, we generated an ARO human thyroidal cancer cell line that expresses the NIS gene (ARO-NIS) and found that its baseline 125I uptake was threefold higher than that of its parental ARO cells. However, a 1-microM all-trans retinoic acid (tRA) treatment significantly increased this 125I uptake up to approximately approximately 6.5-fold on Day 3. tRA also elevated NIS mRNA expression in ARO-NIS cells, with peaks of expression being observed on Day 3. To investigate the underlying genomic mechanisms involved in these tRA-induced phenotypic changes, we subjected tRA-treated and untreated ARO-NIS cells to cDNA microarray analysis. Of 1152, genes spotted onto the microarray membrane, 18 were up-regulated (z ratio>2.0) and 33 were down-regulated (z ratio<-2.0) in ARO-NIS cells after 3 days of tRA treatment. More specifically, tRA increased the expression of BCL3, CSRP3, v-fos, and CDK5 genes and decreased the expression of the FGF12 and IGFBP6 genes. Thus, tRA treatment of human anaplastic thyroid carcinoma cells stably expressing the NIS gene significantly elevates their NIS-mediated radioiodine uptake and alters the expression of many genes involved in cell growth and cellular differentiation. Therefore, tRA treatment and NIS gene transfection are potential tools for the diagnosis and treatment of thyroid cancer.

Semi-Quantitative Analysis of Post-Transarterial Radioembolization (90)Y Microsphere Positron Emission Tomography Combined with Computed Tomography (PET/CT) Images in Advanced Liver Malignancy: Comparison With (99m)Tc Macroaggregated Albumin (MAA) Single Photon Emission Computed Tomography (SPECT).

OBJECTIVES: The purpose of this study is to evaluate the correlation between pretreatment planning technetium-99m ((99m)Tc) macroaggregated albumin (MAA) SPECT images and posttreatment transarterial radioembolization (TARE) yttirum-90 ((90)Y) PET/CT images by comparing the ratios of tumor-to-normal liver counts. METHODS: Fifty-two patients with advanced hepatic malignancy who underwent (90)Y microsphere radioembolization from January 2010 to December 2012 were retrospectively reviewed. Patients had undergone (99m)Tc MAA intraarterial injection SPECT for a pretreatment evaluation of microsphere distribution and therapy planning. After the administration of (90)Y microspheres, the patients underwent posttreatment (90)Y PET/CT within 24 h. For semiquantitative analysis, the tumor-to-normal uptake ratios in (90)Y PET/CT (TNR-yp) and (99m)Tc MAA SPECT (TNR-ms) as well as the tumor volumes measured in angiographic CT were obtained and analyzed. The relationship of TNR-yp and TNR-ms was evaluated by Spearman's rank correlation and Wilcoxon's matched pairs test. RESULTS: In a total of 79 lesions of 52 patients, the distribution of microspheres was well demonstrated in both the SPECT and PET/CT images. A good correlation was observed of between TNR-ms and TNR-yp (rho value = 0.648, p < 0.001). The TNR-yp (median 2.78, interquartile range 2.43) tend to show significantly higher values than TNR-ms (median 2.49, interquartile range of 1.55) (p = 0.012). The TNR-yp showed weak correlation with tumor volume (rho = 0.230, p = 0.041). CONCLUSIONS: The (99m)Tc MAA SPECT showed a good correlation with (90)Y PET/CT in TNR values, suggesting that (99m)Tc MAA can be used as an adequate pretreatment evaluation method. However, the (99m)Tc MAA SPECT image consistently shows lower TNR values compared to (90)Y PET/CT, which means the possibility of underestimation of tumorous uptake in the partition dosimetry model using (99m)Tc MAA SPECT. Considering that (99m)Tc MAA is the only clinically available surrogate marker for distribution of microsphere, we recommend measurement of tumorous uptake using (90)Y PET/CT should be included routinely in the posttherapeutic evaluation.

Radioembolization With Yttrium-90 Resin Microspheres in Hepatocellular Carcinoma: A Multicenter Prospective Study.

OBJECTIVES: The aim of this prospective study was to reveal the efficacy and safety of Yttrium-90 (Y) radioembolization in Korean patients with hepatocellular carcinoma (HCC). METHODS: A total of 40 HCC patients were prospectively recruited from 7 centers. The response to treatment was assessed on the basis of the modified Response Evaluation Criteria in Solid Tumors criteria. The time to progression and overall survival were also evaluated, and the assessment of safety was done according to National Cancer Institute Common Terminology Criteria, Version 3.0. RESULTS: Forty-two treatments of Y radioembolization were carried out. Median follow-up was 29 months. At 3 months, the complete response, partial response (PR), and stable disease were seen in 4 (10.0%), 19 (47.5%), and 15 (37.5%) patients, respectively. The response rate was 57.5% (23/40), and disease control rate was 95% (38/40) at 3 months. The response rate at 6 months was 63.9% (23/36), and disease control rate was 83.3% (30/36). The median time to progression was 18 months. During follow-up, 10 HCC-related deaths occurred and the 3-year survival rate was 75%. In 19 patients with Barcelona Clinic Liver Cancer-B stage, the 3-year survival rate was 50%. The tumor number (>5) was the only significant predictor associated with survival. The most common adverse event was abdominal pain of mild to moderate degree, and all the complications were manageable. Twenty-six (65%) patients underwent other treatments such as transarterial chemoembolization because of local progression or remnant viable lesion. CONCLUSIONS: Y radioembolization might be a safe and effective treatment modality in intermediate-stage to advanced-stage HCC.

Genome-wide expression profiling of 8-chloroadenosine- and 8-chloro-cAMP-treated human neuroblastoma cells using radioactive human cDNA microarray.

Previous reports raised question as to whether 8-chloro-cyclic adenosine 3,5-monophosphate (8-Cl-cAMP) is a prodrug for its metabolite, 8-Cl-adenosine which exerts growth inhibition in a broad spectrum of cancer cells. The present study was carried out to clarify overall cellular affects of 8-Cl-cAMP and 8-Cl-adenosine on SK-N-DZ human neuroblastoma cells by systematically characterizing gene expression using radioactive human cDNA microarray. Microarray was prepared with PCR-amplified cDNA of 2,304 known genes spotted on nylon membranes, employing (33)P-labeled cDNAs of SK-N-DZ cells as a probe. The expression levels of approximately 100 cDNAs, representing about 8% of the total DNA elements on the array, were altered in 8-Cl-adenosine- or 8-Cl-cAMP-treated cells, respectively. The genome-wide expression of the two samples exhibited partial overlaps; different sets of up-regulated genes but the same set of down-regulated genes. 8-Cl-adenosine treatment up-regulated genes involved in differentiation and development (LIM protein, connexin 26, neogenin, neurofilament triplet L protein and p21(WAF1/CIP1)) and immune response such as natural killer cells protein 4, and down-regulated ones involved in proliferation and transformation (transforming growth factor-beta, DYRK2, urokinase-type plasminogen activator and proteins involved in transcription and translation) which were in close parallel with those by 8-Cl-cAMP. Our results indicated that the two drugs shared common genomic pathways for the down-regulation of certain genes, but used distinct pathways for the up-regulation of different gene clusters. Based on the findings, we suggest that the anti-cancer activity of 8-Cl-cAMP results at least in part through 8-Cl-adenosine. Thus, the systematic use of DNA arrays can provide insight into the dynamic cellular pathways involved in anticancer activities of chemotherapeutics.

Implication of lymph node metastasis detected on 18F-FDG PET/CT for surgical planning in patients with peripheral intrahepatic cholangiocarcinoma.

OBJECTIVES: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy after hepatocellular carcinoma. ICC can be divided into 2 types according to their location: peripheral and hilar types. Intense F-FDG uptake on PET was reported in peripheral ICC. However, the usefulness of PET/CT in detecting tumors and predicting prognosis in peripheral ICC has not been fully evaluated. In this study, we evaluated the clinical role of F-FDG PET/CT to predict the recurrence after the curative resection in patients with surgically indicated peripheral ICC. METHODS: Eighteen patients with ICC underwent preoperative CT and F-FDG PET/CT scans. SUVmax of tumor, tumor to normal liver SUV ratio (TNR), lymph node status evaluated by F-FDG PET/CT, tumor and lymph node size measured by CT, vascular invasion confirmed by pathology, and satellite nodules found on CT were compared between 1-year recurrence group and recurrence-free group by chi-square test. RESULTS: Of total 23 measurable lymph nodes, 4 nodes were positive and other 19 nodes were negative or equivocal on CT. Among those 23 nodes, 9 nodes were positive and other 14 nodes were negative on F-FDG PET/CT. The sensitivity and specificity of CT were 20.0% and 86.4%, and those of F-FDG PET/CT were 80.0% and 92.3%. In the comparison between 1-year recurrent and nonrecurrent groups, lymph node metastasis detected on F-FDG PET/CT had statistically positive correlation with the 1-year recurrence after surgical resection (P = 0.02). Other factors showed no statistically significant difference between the groups. CONCLUSION: We found that lymph node metastasis detected on F-FDG PET/CT correlated positively with 1-year recurrence after surgical resection in patients with peripheral ICC.

Detectability of T-Measurable Diseases in Advanced Gastric Cancer on FDG PET-CT.

PURPOSE: Usefulness of FDG PET-CT in monitoring response in locally advanced gastric cancer has been reported. The purpose of this study was to evaluate the related factors to detect measurable diseases in advanced gastric cancer on FDG PET-CT. METHODS: We retrospectively reviewed 38 patients diagnosed as having advanced gastric cancer. We defined the measurable diseases when there was visualized tumor of which maximum standardized uptake value (SUVmax) was higher than 1.35*SUVmax of liver + 2*SD of liver SUV. We evaluated what kinds of factors from the clinicopathologic features were related to identifying measurable diseases. RESULTS: Of 38 patients with advanced gastric cancer, 18 (50 %) had measurable tumors on FDG PET-CT. Measurable tumors were significantly more frequent in well or moderately differentiated adenocarcinoma (70.5 % vs 35.3 %, p < 0.05), in the tumors located at antrum or angle (66.7 % vs 29.4 %, p < 0.05) and in the elderly group (age of 55 years old or more, 72.0 % vs 8.3 %, p < 0.001) than the others, respectively. By multivariate analysis, age at diagnosis was the only independent predictor for the measurable disease on FDG PET-CT. CONCLUSION: We found that age at diagnosis, as well as histologic types and location of tumors, were the affecting factors to detect measurable disease on FDG PET-CT in patients with advanced gastric cancer. Our study suggests that elderly patients of age of 55 years old or more can frequently have T-measurable disease on FDG PET-CT in advanced gastric cancer and FDG PET-CT will be helpful to monitor measurable disease.

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.

Usefulness of Bremsstrahlung Images after Intra-arterial Y-90 Resin Microphere Radioembolization for Hepatic Tumors.

PURPOSE: Y-90 resin microsphere radioembolization is used to treat inoperable hepatic tumors. After injection of Y-90 resin microsphere, the only method to visualize the distribution of Y-90 is the scintigraphic imaging of bremsstrahlung radiation. The purpose of this study was to evaluate the characteristics and usefulness of bremsstrahlung imaging in Y-90 resin microsphere treatment. METHODS: Twenty patients (22 administrations) underwent intra-arterial Y-90 resin microsphere treatment. For pre-treatment planning, images of Tc-99m albumin macroaggregate (MAA) arterial injection and hepatic contrast angiography were obtained. Post-treatment bremsstrahlung images were taken and compared with pre-treatment images. The extrahepatic activity was evaluated on bremsstrahlung images. To correlate the size and vascularity of the tumors with tumor visualization on bremsstrahlung images, the individual tumors were grouped according to visualization on each image and compared with one another by size and tumor-to-normal ratio. RESULTS: All post-therapeutic bremsstrahlung images showed similar contours of the liver with pre-treatment angiography. No extrahepatic activity was seen in all cases. The visualized tumors on bremsstrahlung images were significantly larger than the non-visualized tumors. Tumor-to-normal ratios of the visualized tumors on bremsstrahlung images were significantly higher than those of the non-visualized tumors. CONCLUSIONS: Bremsstrahlung images after intra-arterial Y-90 resin microsphere treatment are useful in evaluating the intrahepatic distribution of radioisotope and detecting possible extrahepatic activity.

Radiation safety issues in y-90 microsphere selective hepatic radioembolization therapy: possible radiation exposure from the patients.

PURPOSE: The purpose of this study was to estimate the possible external radiation dose to other individuals from patients treated with Y-90 resin microspheres for unresectable hepatocellular carcinoma. METHODS: We designed the study prospectively to estimate the possible radiation dose to other individuals from patients who had been treated with Y-90 microspheres for unresectable hepatocellular carcinoma. We estimated the total effective dose equivalent (TEDE) using two methods: 'theoretical' TEDEs according to the administered activity and 'measured' TEDE based on the 'measured' ambient radiation exposure rate. We compared the results from each method to determine when we can release patients from confinement at the earliest time complying with the patient release criteria. RESULTS: A total of 20 administrations of Y-90 resin microspheres were done in 18 patients. The average administered activity was 1.2 ± 0.77 (0.28-2.97) GBq. The 'theoretical' TEDEs were in the range of 0.8-10 µSv. The 'measured' TEDEs were in the range of 2.31-185 µSv. The measured TEDEs tend to be higher than the theoretical TEDEs. The values of theoretical and measured TEDE were both far less than 1 mSv, the upper limit at which the licensee can release a patient without any written documents. CONCLUSION: The effective dose equivalent caused by the Y-90 microsphere administered patient is very low. It is safe in terms of radiation safety to the other individuals when Y-90 microsphere radioembolization therapy is done with dose less than 3 GBq. Because the measured TEDE tends to be higher than the theoretical TEDE, it is recommended to use 'measured' TEDE for determining patient release.

The prevalence of atopy and asthma among university freshmen in Seoul, Korea: association with obesity.

The aims of this study were to investigate the prevalence of atopy, asthma, and obesity in university freshmen and to determine whether leptin is associated with bronchodilator reversibility in obesity. A total of 537 university freshmen completed International Study of Asthma and Allergies in Children (ISAAC) questionnaire and underwent skin prick testing and bronchodilator reversibility test. The prevalences of asthma, wheeze, and atopy were 10 (1.9%), 84 (15.6%), and 198 (36.9%), respectively. The mean (+/- SD) bronchodilator response (5.1 +/- 4.4%) was higher in the overweight/obese men than in the normal male subjects (3.7 +/- 3.2%, p < 0.05). The mean leptin level in the overweight/obese men was 5.55 +/- 3.48 ng/mL, which was significantly higher than that (2.78 +/- 1.65 ng/mL) of the normal male subjects. The prevalence of asthma among university freshmen is seriously under-diagnosed and leptin may play a role in bronchodilator reversibility in overweight/obese young men.