Preliminary And Clinical Studies On Positron Emission Tomography

Purpose and Project design:Brain tumors can be classified by origin into primary or metastatic. Primary brain tumor has a high occurrence ranking the 11^th in all malignant tumors.The most common type of primary brain tumor is glioma.Despite improvements in various treatment strategies,median survival of patients is limited,especially the high grade tumor;the metastatic brain tumor has a even higher occurrence with a possibility of 20-40%in all tumor patients.Computed tomography(CT) and magnetic resonance imaging(MRI) with their enhanced imaging are now the routine methods of brain tumor diagnosis.With the development of positron emission tomography(PET), it has been applied in various ways of brain tumor imaging including malignancy differentiation,pre-operation grading,staging, post-treatment monitoring,stereotaxis needle biopsy,radiation treatment planning,prognosis prediction,etc.With the foundation of various radiopharmaceuticals,especially the classic 2-[¹⁸F]fluoro-2-deoxy-D-glucose(FDG),PET can provide the biological information of tumor metabolism that neither CT nor MRI can.The biological tumor volume (BTV) is a newly developed concept including the blood infusion, metabolism,proliferation activity,tumor specific receptor,vascular generation,etc.of the tumor.To define such BTV,FDG only is far from enough.Due to the high uptake of FDG in cerebral cortex,brain tumor imaging with FDG is limited in specificity and sensitivity of low grade tumor.Other radiopharmaceuticals like amino-acid,choline,acetate,etc. are needed to provide more accurate diagnosis and delineation of the tumor.This study intended to evaluate the imaging quality of 11C labeled tracers,their liability in brain tumor diagnosis and the application in radiation treatment planning of brain tumor. Results:Partâ… Study of ¹¹C-PET imagingThis part of study includes 4 experiments.Experiment 1:PET/CT imaging of Hoffman 3D brain model using multiple positron radiopharmaceuticals.Comparing the results in hot region,cold region,linearity and homogeneity,our study showed no significant difference in image resolution between ¹¹C- and ¹⁸F- labeled tracers. However,in small hot regions there is certain aberration in resolution test with ¹¹C-labeled images compared to ¹⁸F-labeled images and all results showed mild deviation in both hot and cold region,which should be taken into consideration in clinical use.Experiment 2:I established brain tumor imaging model in Hoffman 3D brain model.The sizes of the tumor models were 5mm and 15mm in diameter.MRI showed the actual size of the tumor while in PET imaging,different background concentration of the radiopharmaceuticals(1:5 and 1:10) has certain impact in accessing of tumor size.Tumors with high uptake were likely to be over-accessed,which should be taken into consideration in clinical use.Experiment 3:I applied the tumor model in two different radiation treatment systems(clinical 600-C of Varian and Cyber knife of Accuray). Images of the model were transferred through compact disc into the treatment planning system(TPS) and adjusted to meet the requirement. Target delineation was performed with fused images.My study showed that radiation treatment planning using PET imaging is feasible and can be applied into clinical use.Experiment 4:8 patients with glioma were studied using PET imaging and MRI with contrast.Our study indicated that ¹¹C-Choline PET showed the largest area of the tumor including the sub-clinical infiltrating area which consist mostly with the actual treatment planning area;the result of MRI was closest to the solid part of the tumor;result of ¹⁸F-FDG PET was smaller than the solid part of the tumor but there is no statistical significance compared to the result of MRI.In conclusion,our study showed that ¹¹C-Choline PET was the most suitable imaging technology among the three methods in radiation treatment planning of brain tumors. Partâ…¡The diagnostic value of ¹¹C-Choline combined with ¹⁸F-FDG PET imagingI studied 178 cases of brain tumor with MRI,¹¹C-Choline PET,¹⁸F-FDG PET imaging.Out study showed that the diagnostic sensitivity and specificity of MRI was higher than ¹⁸F-FDG PET but similar as ¹¹C-Choline PET.MRI is superior in showing the anatomical structure but inferior in revealing the biological activities.¹¹C-Choline PET is the most accurate method among all three in locating the tumor;it also showed value in tumor grading and differentiating necrosis from recurrence.Partâ…¢PET/CT in differentiating necrosis from recurrence of brain tumorsI studied 55 cases of post-radiation brain tumor with MRI,¹¹C-Choline PET, ¹⁸F-FDG PET imaging.My study showed that ¹¹C-Choline PET could improve the diagnostic accuracy in differentiating necrosis from recurrence.The accuracy of ¹¹C-Choline PET was 90.9%,which was significantly higher than ¹⁸F-FDG PET and MRI.However,there was still certain rate of false positive and false negative and clinical information and MRI with contrast have great importance in diagnosis.Partâ…£The application of PET/CT in radiation treatment planning of brain tumorsUsing Biograph Sensation 16 and Biograph 64 HD PET/CT scanner of Siemens, clinical 600c of Varian and PEACOCK TPS of Nomos,44 patients with brains tumors were studied with 11C-Choline PET.Metal radio-active points(18F) and laser beams were used for alignment.The acquired data was transferred to TPS through compact disc.The target delineation was performed by radiation therapists and nuclear medicine physicians based on fused images.Patients were closely monitored for symptoms and early reaction of radiation and were accessed 3 months later.I established the methodology of incorporating non-FDG PET/CT imaging in PEACOCK radiation treatment planning.Among all 44 patients,28(63.64%) patients significantly changed their treatment plan due to PET/CT,14 (31.82%)patients increased the target volume and 14(31.82%) decreased. All patients were treated successfully.The application of PET/CT will increase the accuracy of biological target volume planning and increase the possible of clinical remission.Conclusion:1.There is no significant difference in resolution between ¹¹C-labeled and ¹⁸F-labeled tracers.In small hot regions there is certain aberration in resolution test with ¹¹C-labeled images compared to ¹⁸F-labeled images and all results showed mild deviation in both hot and cold region. Different background concentration of the radiopharmaceuticals has certain impact in accessing of tumor size.Tumors with high uptake were likely to be over-accessed.Radiation treatment planning using PET imaging is feasible.¹¹C-Choline PET showed most consistent result with the target volume which could be used in delineating biological target volume.2.MRI with contrast is the conventional method currently in brain tumor imaging,PET/CT plays a compensate role.MRI is superior in showing the anatomical structure but inferior in revealing the biological activities. ¹¹C-Choline PET is the most accurate method among all three in locating the tumor;it also showed value in tumor grading and differentiating necrosis from recurrence.3.PET/CT has important value in differentiating post-radiation necrosis from recurrence of brain tumors.The diagnostic accuracy of ¹¹C-Choline PET/CT was 90.9%,which was significantly higher than MRI and ¹⁸F-FDG PET/CT.There was still certain rate of false positive and false negative and clinical information and MRI with contrast have great importance in diagnosis.4.In radiation treatment of gliomas,CT,MRI and PET imaging provided compensative information in treatment planning.PET/CT can be applied to delineating biological target volume that improves the planning accuracy and therapeutic effect.Limited by the spatial resolution,background uptake,etc.,treatment planning requires multiple methods of imaging. The combined use of multiple radiopharmaceuticals including ¹¹C-Choline, ¹¹C-acetate,¹⁸F-FDG,with conventional CT,MRI and clinical information leads to the future of diagnosis and treatment with PET in brain tumors.