Initial Translational Research From Glucose Metabolism Molecular Imaging Of Non-small Cell Lung Cancer To PDTX Models

PART 1 PET/CT-guided percutaneous FDG-avid metastatic bone biopsy in advanced lung cancer patients:A safe and effective techniqueObjective:18F-FDG PET/CT should be performed before a diagnostic biopsy site is chosen in cases of high clinical suspicion for aggressive,advanced tumors.The aim of this study was to evaluate the safety and efficacy of 18F-FDG PET/CT in guiding metastatic bone biopsies in advanced lung cancer patients.Methods:Fifty-one consecutive patients with suspected lung cancer and 18F-FDG-avid bone lesions underwent PET/CT-guided percutaneous core biopsies after whole body 18F-FDG PET/CT scans.One tissue sample was taken from each patient.Final diagnosis was established on the basis of the histology results.A systematic evaluation of the histopathological results and molecular testing was performed.Results:A total of 53 samples were obtained for histological examination or molecular testing as a second biopsy was required in two patients whose first biopsy pathological diagnosis was unclear.Pathological diagnosis and lung cancer classification were confirmed in 48 patients(48/51).Based on epidermal growth factor receptor(EGFR)mutation tests performed in 23 cases,the total mutation rate of bone metastasis was 30.4%(7/23).Anaplastic lymphoma kinase(ALK)mutation tests were examined in 19 cases with a bone metastasis mutation rate of 31.6%(6/19).Two biopsies were positive for non-Hodgkin lymphoma(NHL)(2/51)and one case was positive for metastatic renal cell carcinoma(RCC).The one-time diagnostic success rate of biopsy was 96.1%(49/51)and the overall diagnostic success rate and sensitivity was 100%.All 51 patients were eventually confirmed as stage IV.No serious complications were encountered and the average biopsy time was30 minutes.Conclusion:PET/CT-guided percutaneous 18F-FDG-avid metastatic bone biopsy is an effective and safe method which yields a high diagnostic success rate in cases of hypermetabolic bone lesions in patients with suspected advanced lung cancer.PART 2 Initial translational research of PDTX Models in NSCLCObjective:Patient-derived tumor xenograft(PDTX)models closely retain the features of the original clinical tumors,offering a powerful tool for tumor biology researches and preclinical drug efficacy testing.Our study aimed to establish PDTX non small cell lung cancer(NSCLC)models,discuss the biological stability of them,and initially explore 18F-FLT and 18 F-FDG uptake as an indicator of tumor response early after individual treatment using PET/CT,to further provide a basis for clinical.Methods:NSCLC tissues from 13 patients were collected in this study,with 10 tumor tissues were obtained by pulmonary resection and 3 tumor specimens were obtained from PET/CT-guided percutaneous target biopsies,and implanted into immuno-deficient mice.Hematoxylin and eosin(H&E)staining and immunohistochemistry(IHC)were performed to confirm the histopathology and molecular biology characteristics of xenografts.18F-FLT and 18F-FDG PET/CT imaging were performed before treatment,24 hours after individual treatment on PDTX models,explore the value of 18F-FLT and 18F-FDG uptake as an indicator of tumor response early after individual treatment.Results:A total of 4 passable PDTX models were successfully established,representing a tumor take rate of 30.8%.And all of them steadily spread to the second generation and one case spread to the third generation.The PDTX NSCLC tissues stained for H&E staining and diagnostic markers(CK5/6,P63,TTF-1,NapsinA,Ki67 and.et)exhibited a similar morphology and immunophenotype to that of the patient tissues from which the primary model was derived.The specificity and tumor's uptake of 18F-FLT prior treatment were higher than 18 F-FDG;3 PDTX models of 18F-FDG uptake in tumor decreased early 24 hours after chemotheraphy.Conclusion:These PDTX NSCLC models provide an ideal platform for individual treatment drug screening and evaluation.18F-FLT and 18F-FDG are both valuable in the early evaluation of NSCLC treatment.The two indicators were even expected to become an effective tool for the early individualized therapy evaluation of PDTX models.