Evaluation of the diagnostic efficacy of 18 F-Fluorine-2-Deoxy-D-Glucose PET/CT for lung cancer and pulmonary tuberculosis in a Tuberculosis-endemic Country.

OBJECTIVE: To determine the diagnostic efficacy of 18 F-FDG PET/CT in distinguishing between pulmonary tuberculosis (PTB) and lung cancer in solitary pulmonary nodule (SPN) in a country with a high prevalence of PTB. METHODS: Patients with SPN who underwent 18 F-FDG PET/CT imaging were retrospectively included in the study. The final diagnosis was established by histopathology. A linear regression equation was fitted to a scatter plot of size and SUVmax of lung cancer and PTB. ROC was used to determine the optimal cutoff values and diagnostic accuracy of 18 F-FDG PET/CT in PTB and lung cancer. RESULTS: About 514 patients were included with the mean age of 57.5 ± 10.6 years. Four hundred and seventy-five cases were diagnosed as lung cancer, and 39 cases were PTB by histopathology. 18 F-FDG PET/CT had sensitivity, specificity, and diagnostic accuracy of 96.0%, 48.7%, and 92.0%, respectively. Utilization of SUVmax ≥2.5 in SPN resulted in 2 and 11 false positives cases of lung cancer and PTB, respectively, whereas SUVmax <2.5 resulted in 18 and 10 false-positive cases of lung cancer and PTB, respectively. The SUVmax and the size of short-axis in the lung cancer group were statistically higher than those in the PTB group. The linear regression equation parameters indicated the slope of the regression line of lung cancer was greater than that of PTB. The ROC curve demonstrated the SUVmax cutoff values of 4.85 and 2.25 for lung cancer and PTB, respectively for predicting the diagnostic accuracy of 18 F-FDG PET/CT. CONCLUSION: 18 F-FDG PET/CT has a higher sensitivity and diagnostic accuracy for malignant SPN. However, it has high false-positive rate and low specificity in tuberculosis endemic areas. Neither SUVmax nor the sizes of the nodules are valuable parameters for distinguishing between lung cancer and PTB. However, the SPN with larger short-axis and higher SUVmax would be inclined to malignant tumor.

Preclinical Evaluation of a Fluorine-18 (18F)-Labeled Phosphatidylinositol 3-Kinase Inhibitor for Breast Cancer Imaging.

Breast cancer is one of the commonest malignancies in women, especially in middle-aged and elderly women. Abnormal activation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKt/mTOR) pathway has been found to be involved in breast cancer proliferation. Pictilisib (GDC-0941) is a potent inhibitor of PI3K with high affinity and is undergoing phase 2 clinical trials. In this study, we aimed to develop a noninvasive PI3K radiotracer to help determine the mechanism of the PI3K/AKt/mTOR pathway to aid in diagnosis. We designed a new 18F-radiolabeled radiotracer based on the structure of pictilisib, to evaluate noninvasively abnormal activation of the PI3K/AKT/mTOR pathway. To increase the water solubility, and to decrease hepatobiliary and gastrointestinal uptake of the tracer, pictilisib was modified with triethylene glycol di(p-toluenesulfonate) (TsO-PEG3-OTs) to obtain TsO-PEG3-GDC-0941 as the precursor for 18F labeling. A nonradiolabeled reference compound [19F]-PEG3-GDC-0941 was also prepared. Breast cancer cell lines, MCF-7 and MDA-MB-231, were used as high- and low-expression PI3K models, respectively. PET imaging and ex vivo biodistribution assays of [18F]-PEG3-GDC-0941 in MCF-7 and MDA-MB-231 xenografts were also performed, and the results were compared. The precursor compound and reference standard compound were successfully synthesized and identified using NMR and mass spectroscopy. The 18F radiolabeling was achieved with a high yield (61 ± 1%) at a high molar activity (2100 ± 100 MBq/mg). MicroPET images and biodistribution studies showed a higher uptake of the radiotracer in MCF-7 tumors than in MDA-MB-231 tumors (7.56 ± 1.01%ID/g vs 4.07 ± 0.68%ID/g, 1 h postinjection). Additionally, the MCF-7 tumor uptake was significantly decreased when a blocking dose of GDC-0941 was coinjected, indicating high specificity. The liver was found to be the major excretory organ with 5.82 ± 0.88%ID/g at 30 min postinjection for MCF-7 mice. This radiotracer holds great potential for patient screening, diagnosis, and therapy prediction of PI3K-related diseases.

18F-Fluoro-2-Deoxy-d-Glucose PET/Computed Tomography Evaluation of Lung Cancer in Populations with High Prevalence of Tuberculosis and Other Granulomatous Disease.

Pulmonary tuberculosis infects one-third of world's population and is responsible for the high mortality and morbidity in developing countries. The presence of a high number of macrophages and lymphocytes in active tuberculosis granulomas is associated with high uptake of 18F-fluoro-2-deoxy-d-glucose on PET imaging mimicking lung cancer. In many cases, radiological features of pulmonary tuberculosis are undistinguishable from lung cancer, which makes the diagnosis difficult. Clinical history and computed tomographic (CT) findings on a hybrid PET/CT are as important as findings on a PET in the diagnosis of lung cancer.