Haoping Xu

The role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography whole body imaging in the evaluation of focal thyroid incidentaloma

Background: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) is a non-invasive whole-body imaging technique used to evaluate various types of malignancies. Recent advances have rapidly developed it into a diagnostic imaging tool in oncology. Objectives: In this study, the prevalence of thyroid incidentaloma and its cancer risk rate were investigated by 18F-FDG PET/CT. The threshold of maximal standardized uptake value (SUVmax) for differentiation of benign and malignant tumors was also defined. Methods: From June 2007 to December 2008, 3600 subjects underwent 18F-FDG PET/CT in our department. Among the population under study, 115 subjects developed focal increased 18F-FDG uptake as thyroid incidentalomas and their SUVmax were analyzed qualitatively and semi-quantitatively. Results: Data from the 18F-FDG PET/CT study suggested that overall prevalence of thyroid incidentaloma was 3.2% (115/3580). Among the 96 incidentalomas (20 confirmed by surgery; 76 confirmed by fine-needle aspiration) with additional cyto- and histopathological diagnoses, 50% were malignant thyroid lesions. Therefore, the cancer risk of thyroid incidentaloma was 50%. SUVmax values of the malignant samples were significantly higher than those of benign (p=0.00, p<0.05). A SUVmax above 8 tended to be malignant. A significant correlation between SUVmax and maximal diameter of the thyroid incidentaloma was also indicated. Conclusions: Thyroid incidentaloma detected by 18F-FDG PET/CT has higher risk rate for thyroid malignancy; SUVmax can be used for differentiating benign from malignant thyroid tumors.

The Role of 18F-FDG PET/CT in the Evaluation of Ascites of Undetermined Origin

The first aim of our study was to compare the role of 18F-FDG PET/CT with that of CT alone in detecting the primary cause of ascites. A secondary aim was to compare the value of 18F-FDG PET/CT with that of CT alone in detecting abdominal cavity metastasis. Finally, we analyzed the receiver-operating-characteristic (ROC) curves of maximal standardized uptake values (SUVmax), serum carcinoembryonic antigen, CA19-9, and CA12-5 for differential diagnostic abilities. Methods: The 18F-FDG PET/CT scans of 40 patients with ascites of undetermined origin, including 30 patients with malignant diseases and 10 with benign lesions, were reviewed for the presence of ascites. Among the 40 patients, 34 had received their diagnosis by pathologic examination and 6 by clinical follow-up. We also assessed the 18F-FDG PET/CT scans of 20 healthy volunteers for comparison. All 18F-FDG PET/CT images were visually interpreted, and the SUVmax was measured. We compared the mean diameter of true-positive lesions with that of false-negative lesions. The diagnostic abilities of SUVmax, serum carcinoembryonic antigen, CA19-9, and CA12-5 were compared using the ROC curve. Results: The sensitivity, specificity, and accuracy of PET/CT in detecting the primary cause of ascites were 63.3% (19/30), 70.0% (7/10), and 65.0% (26/40), respectively, and those of CT alone were 36.7% (11/30), 80% (8/10), and 47.5% (19/40), respectively (sensitivity, P < 0.05). The sensitivity of PET/CT was higher than that of CT alone for detecting abdominal cavity metastasis (86.4% vs. 27.3%, P < 0.01). The SUVmax in patients with malignant primary and metastatic lesions was significantly higher than that in healthy volunteers and in patients with benign ascites (P < 0.05). The mean maximal diameter of false-negative lesions was significantly smaller than that of true-positive lesions (P < 0.05). In ROC analysis, the areas under the curve of SUVmax, serum carcinoembryonic antigen, CA19-9, and CA12-5 were 0.803 (P < 0.01), 0.773 (P < 0.05), 0.552 (P > 0.05), and 0.220 (P < 0.01), respectively. Conclusion: 18F-FDG PET/CT assisted in detecting the original cause of ascites. The differential diagnostic ability of 18F-FDG PET/CT was superior to that of CT alone, tumor markers, and cytology. More attention should be paid to peritoneal tuberculosis, which can markedly accumulate 18F-FDG and mimic peritoneal carcinoma.

The role of integrated 18F-FDG PET/CT in identification of ectopic ACTH secretion tumors

The role of 18F-Flurodeoxyglucose positron emission tomography (18F-FDG PET) scan in localization of ectopic Cushing’s syndrome (EAS) tumor is still controversial. Here, we report on the use of integrated 18F-FDG PET and computed tomography (18F-FDG PET/CT) in localization of EAS tumors in patients with ectopic Cushing’s syndrome. Five patients, three men and two women, were reported, whose endocrine investigations and negative pituitary imaging were suggestive of ectopic ACTH secretion. 18F-FDG PET/CT was performed to identify the source of ACTH secretion. Then the patients were suggested to perform pathologic examination. It turned out that all of these five patients have abnormal markedly intense FDG uptake lesions on 18F-FDG PET/CT images. Four of them underwent lesion resection, whose plasma ACTH and serum cortisol levels returned to normal after the surgery. Also, they were at last remission from all the symptoms. Pathologic results showed one thymic carcinoid, one pulmonary carcinoid, one thymoma, and one pulmonary carcinoid with upper mediastinum carcinoid. Unfortunately, one patient died due to severe infection and electrolyte disorders. 18F-FDG PET/CT technology integrates PET and CT imaging in one device so as to increase the accuracy of tumor localization and further improve the prognosis of the patients by curative resection.

Retinoic acid and tributyrin induce in-vitro radioiodine uptake and inhibition of cell proliferation in a poorly differentiated follicular thyroid carcinoma.

ObjectiveRadioiodine ablation is ineffective in patients with radioiodine nonresponsive thyroid carcinoma. We investigated the effects of all-trans retinoic acid (ATRA) combined with histone deacetylase inhibitor, tributyrin on sodium-iodide symporter (NIS) expression, radioiodine uptake, and inhibition of cell proliferation in a poorly differentiated follicular thyroid carcinoma (FTC-133) in vitro. MethodsFTC-133 cells were cultured in the presence of ATRA and tributyrin either as a single agent or in combinations for 48 h. The expression of NIS mRNA and protein was, respectively, detected by quantitative real-time polymerase chain reaction and western blot. The radioiodine uptake was determined after incubation of FTC-133 cells with 125I-iodide. Finally, the cell proliferation test of FTC-133 was performed after treatment. ResultsEnhanced expression of NIS mRNA and protein was observed in FTC-133 cells treated with ATRA and tributyrin, which further resulted in significant higher levels of radioiodine uptake than that of untreated control cells and cells treated with ATRA alone. Additive inhibition of the proliferation of FTC-133 cells was also observed with the combination of ATRA and tributyrin. ConclusionThe combination of ATRA and tributyrin induced a synergistic effect on radioiodine uptake and inhibition of FTC-133 cells proliferation in vitro. However, further in-vivo studies and additional molecular research will be needed to determine the absolute efficiency of radioiodine therapy.

Sodium butyrate enhances the expression of baculovirus-mediated sodium/iodide symporter gene in A549 lung adenocarcinoma cells.

ObjectiveIncreased expression of sodium/iodide symporter (NIS) is required for reporter gene imaging and effective radioiodine treatment of tumor. We investigated whether increased accumulation of iodine can be induced by sodium butyrate through a newly developed baculoviral transfer of the human NIS (hNIS) gene in A549 human lung adenocarcinoma. MethodsA recombinant baculovirus [Bac–cytomegalovirus (CMV)–hNIS] encoding hNIS gene under the control of the CMV promoter was constructed. After A549 cells were transfected with Bac–CMV–hNIS in the presence of sodium butyrate, the expression of hNIS protein was detected by immunofluorescence and western blot analysis. The uptake and efflux of iodine were determined after the incubation of the transfected cells with 125I-iodide in the presence or absence of sodium butyrate. ResultsImmunocytochemical staining and western blot analysis showed increased hNIS protein expression in A549 cells transfected with Bac–CMV–hNIS after sodium butyrate treatment. Bac–CMV–hNIS transfected A549 cells accumulated up to about nine times more 125I than nontransfected cells; the amount of 125I uptake increased in a sodium butyrate in dose-dependent manner (P<0.001). However, rapid efflux of radioactivity was observed, with 50% lost during the first 2 min after 125I-containing medium had been replaced by a nonradioactive medium. ConclusionOur results indicated that an improved efficiency of baculovirus-mediated hNIS reporter gene imaging in lung adenocarcinoma is possible with treatment with sodium butyrate. However, additional conditions need to be defined to reduce the rapid efflux of radioiodine for the purpose of radionuclide therapy.

Feasibility of a novel positive feedback effect of 131I-promoted Bac-Egr1-hNIS expression in malignant glioma through baculovirus: a comparative study with Bac-CMV-hNIS.

ObjectiveIncreased expression of sodium iodide symporter (NIS) is required for reporter gene imaging and effective radioiodine treatment of tumor. As the early-growth response-1 (Egr1) promoter is activated by radioisotopes, the existence of a positive feedback effect of 131I-promoted Egr1–hNIS expression is possible. Compared with a widely used cytomegalovirus (CMV) promoter, we investigated a possible increased activity of 131I-stimulated human NIS (hNIS) transgene expression in malignant glioma using a baculovirus vector containing the Egr1 promoter. MethodsRecombinant baculovirus (Bac–CMV–hNIS) encoding the hNIS gene under the control of the CMV promoter and Bac–Egr1–hNIS encoding the hNIS gene under the control of the radiation-inducible Egrl promoter were constructed. After human malignant glioma U87 cells were transfected with Bac–CMV–hNIS or Bac–Egr1–hNIS, stimulated with or without 131I, the expression of the hNIS protein was detected by immunofluorescence and a flow cytometry test. The uptake and efflux of iodine were determined after the incubation of the transfected cells with 131I. ResultsImmunocytochemical staining and flow cytometry test showed a lower hNIS protein expression in U87 cells transfected with Bac–Egr1–hNIS (even after 131I stimulation) compared with U87 cells transfected with Bac–CMV–hNIS. Bac–CMV–hNIS-transfected U87 cells accumulated up to approximately 25.8 times more 131I than nontransfected cells, whereas Bac–Egr1–hNIS-transfected U87 cells accumulated up to approximately 3.5 and 14.2 times more 131I pre-stimulation and post-stimulation. However, rapid efflux of radioactivity was observed in both groups, with 50% lost during the first 2 min after the 131I-containing medium was replaced by a nonradioactive medium. ConclusionOur results indicated that an improved transgene expression of 131I-stimulated hNIS in U87-malignant glioma cells using a baculovirus vector containing the Egr1 promoter is possible, but the expression level is lower than that of Bac–CMV–hNIS-transfected U87 cells. However, it might be an approach to improve the specificity of gene therapy using radiosensitive promoters to activate hNIS gene expression selectively in the radiation field.

Feasibility of a novel positive feedback effect of 131I-promoted Bac-Egr1-hNIS expression in malignant glioma via baculovirus

PURPOSE As intracellular iodine is released rapidly, increased expression of sodium/iodide symporter (NIS) is required for effective radioiodine treatment of tumor. As Egr1 promoter is activated by ¹³¹I and may promote human NIS (hNIS) expression, hNIS also induces ¹³¹I uptake and activates Egr1, so the existence of a positive feedback effect of ¹³¹I-promoted Egr1-hNIS expression is possible. Our purpose was to investigate the possible existence of this positive feedback effect through a series of in vitro pioneer studies. METHOD Recombinant baculovirus (Bac-Egr1-hNIS) encoding the hNIS gene under the control of a radiation-inducible Egrl promoter was constructed. To test ¹³¹I-promoted hNIS expression, human malignant glioma U87 cells were transfected with Bac-Egr1-hNIS, stimulated with or without ¹³¹I; the expression of hNIS protein was detected by immunofluorescence and flow cytometry test. In addition, the uptake and efflux of ¹³¹I were determined after the incubation of Bac-Egr1-hNIS-transfected U87 cells with or without ¹³¹I. RESULTS Immunocytochemical staining and flow cytometry test showed a higher hNIS protein expression in Bac-Egr1-hNIS-transfected U87 cells with ¹³¹I stimulation than in cells without stimulation. Bac-Egr1-hNIS-transfected U87 cells accumulated up to about 4.05 times of ¹³¹I after ¹³¹I stimulation. The amount of ¹³¹I uptake in both groups showed a baculovirus dose-dependent manner. However, rapid efflux of radioactivity was observed in both groups, with 50% lost during the first 2 min after the ¹³¹I-containing medium had been replaced by a nonradioactive medium. CONCLUSION Our results indicated that an improved transgene expression of ¹³¹I-stimulated hNIS in U87 cells using a baculovirus vector containing the Egr1 promoter is possible, and the increased expression of hNIS is responsible for a higher ¹³¹I uptake. It might provide a reference for the existence of a positive feedback effect in ¹³¹I-promoted Bac-Egr1-hNIS expression in malignant glioma and is an interesting aspect of NIS-related studies.