Systematic Review Of The Diagnosis Of ¹⁸F-FDG PET In Pulmonary Nodules And Animal Experiment Study On ¹¹C-PDT PET In Lung Carcinoma

Background:Lung cancer is one of the most familiar malignant tumors in the world. The incidence rate and death rate increased significantly recent years, which drew the attention of many researchers to the diagnosis of lung cancer. Positron emission tomography (PET) is a rapidly developing new imaging technique in the diagnosis and staging of lung cancer. There are two parts in this study. In Part 1, systematic review of the diagnosis of ¹⁸F-FDG PET in solitary pulmonary nodules was done, and in Part 2, the biodistribution and PET imaging of a new tracer, ¹¹C-PDT, in murine model were investigated.Objective:The study objective of Part 1 was to determine the diagnostic accuracy of FDG-PET in patients with solitary pulmonary nodules (SPN) using Meta-analysis method and to find the method to improve the diagnostic accuracy by systematic review. In Part 2, the objective was to investigate the biodistribution and PET imaging of ¹¹C-PDT in murine model of lung carcinoma, to study the biodistribution and PET imaging of ¹¹C-PDT in murine model of inflammation, and to evaluate the use of ¹¹C-PDT as a new PET tracer for monitoring tumor response to chemotherapy and radiotherapy.Methods:In Part 1, systematic review and Meta-analysis of clinical studies regarding FDG-PET and SPN was conducted. Studies were identified by a comprehensive search of the PubMed, Medline, CBM databases. The studies were then selected by the criteria for inclusion and exclusion according to the criteria of diagnostic research. The methodologic quality of the included studies was assessed by two reviewers independently. Many statistics softwares were adopted in the statistical analysis. After the test of heterogeneity, fixed or random statistical effect model was selected. After Meta-analysis of these studies, sensitivity, specificity, and other measures of accuracy of FDG-PET in the diagnosis of SPN were pooled using proper models. Summary receiver operating characteristic (SROC) curves were used to summarize overall test performance. Sources of heterogeneity were studied by sensitivity analysis and meta-regression, and the publication bias was also evaluated. Then the cases which were diagnosed falsely in the included studies were systematic reviewed and analysised. The missed diagnosis rate and misdiagnosis rate were compared individually with different diagnostic PET units and different diagnostic methods. All the false positive and false negative cases were summarized, and the information of their diameters and pathological diagnosis was analysised. In Part 2, the biodistribution and PET imaging of ¹¹C-PDT were performed in animal model. Thirty mice bearing the lung adenocarcinoma were divided into five groups according to the different tracers and time after injection at random. The biodistribution of mice for ¹¹C-PDT was measured with well-gamma detector at 7min, 15min, 30min, 60min after injection from tail veins. And the biodistribution of mice for ¹⁸F-FDG was examined at 60min after injection as controls. In addition, the PET imaging of mice was performed using the two tracers. Twelve mice with inflammation were divided into two groups according to the different tracers at random. The biodistributionof mice for ¹¹C-PDT and ¹⁸F-FDG was measured with well-gamma detector at 60 min after injection. The PET imaging of mice was also performed using the two tracers. Thirty-six mice bearing the lung adenocarcinoma were divided into two groups according to two radioactive tracers at random. Each group was also divided into three groups: untreated controls; 1 d after chemotherapy; 2 d after chemotherapy. The mice of chemotherapy groups were treated with cisplatin. All mice were injected with ¹¹C-PDT or ¹⁸F-FDG. Tumor biodistribution of all mice was measured with well-gamma detector 60 min after injection and the PET imaging of mice was performed. Thirty-six mice bearing the lung adenocarcinoma were divided into six groups similar to the chemotherapy treatment. The mice of radiotherapy group were treated with X-ray irradiation of 20 Gy. All mice wereinjected with ¹¹C-PDT or ¹⁸F-FDG from tail veins. Tumor biodistribution of all mice was measured 60 min after injection and the PET imaging of mice was also performed.Results:In Part 1, based on the including and excluding criteria, 26 studies were selected for Meta-analysis finally. The pooled sensitivity and specificity with their corresponding 95 % CI of FDG-PET in the diagnosis of solitary pulmonary nodules were 0.94(0.91～0.95), 0.86(0.82～0.89), respectively. The pooled dOR of 83.63(53.05～131.84) suggests a high diagnostic accuracy for PET. Area under curve (AUC) of SROC was 0.955 and Q^* index was 0.897. Multiple regression analysis suggest that the difference for studies with or without blinded, consecutive/random, and prospective designs and so on, did not reach statistical significance, indicating that the study design did not substantially affect the diagnostic accuracy. The funnel plots for publication bias show no obvious asymmetry, and it indicated that the pooled results were not influenced by the publication bias. There were 62 false positive cases and 50 false negative cases in all the included studies. The compare analyse suggest that there was no statistical significance for studies with different diagnostic PET units or different diagnostic methods. In Part 2, at the biodistribution study of ¹¹C-PDT, considerable radioactive uptake of tumor was observed, and much radioactivity was showed in liver and kidney. The ratios of tumor/muscle were above 2.0 at 60 min after injection. The tumor PET images with ¹¹C-PDT were clear. The ratios of inflammation/muscle of ¹⁸F-FDG were higher than those of ¹¹C-PDT. Inflammatory tissues were visible only in ¹⁸F-FDG PET images. Tumor ¹¹C-PDT uptake decreased gradually after treatment of cisplatin. The drug-induced reduction of ¹¹C-PDT uptake in tumor was more pronounced significantly than that of ¹⁸F-FDG. The PET imaging confirmed lower tumor ¹¹C-PDT retention after chemotherapy. Tumor ¹¹C-PDT uptake also decreased gradually after radiotherapy. The reduction of ¹¹C-PDT uptake in tumor was same to that of ¹⁸F-FDG. The PET imaging confirmed lower tumor ¹¹C-PDT retention after radiotherapy.Conclusions:The articles entered into this Meta-analysis were of high quality. FDG-PET is an accurate noninvasive imaging test for diagnosis of SPN, and FDG-PET is likely to be a useful tool for differential diagnosis of SPN. FDG PET is more efficient in positive diagnosis, but its intermediate specificity for malignancy is its shortcoming. False positive results offen occur in nodules of tuberculosis and fungous infection with increased glucose metabolism, and little correlate with the diameters of the nodules. False negative results often occur in the nodules with small diameter, and adenocarcinoma is the most pathological type. In the animal studies, the uptake of ¹¹C-PDT in lung carcinoma tissues was higher than that in muscle tissues, thus the pulmonary neoplasm could be identified with PET imaging. Inflammatory tissues were invisible in ¹¹C-PDT PET images, so that ¹¹C-PDT has a higher tumor specificity. The uptake of ¹¹C-PDT in tumor decreased after chemotherapy and radiotherapy, therefore, ¹¹C-PDT is a promising PET tracer for monitoring response to therapy in oncology.