Date of Graduation
5-2014
Document Type
Dissertation (PhD)
Program Affiliation
Biomedical Sciences
Degree Name
Doctor of Philosophy (PhD)
Advisor/Committee Chair
David J Yang
Committee Member
Franklin C Wong
Committee Member
Wendy A. Woodward
Committee Member
Zhongxing Liao
Committee Member
Osama R Mawlawi
Abstract
Among radiopharmaceuticals of positron emission tomography (PET), 18F-Fluorodeoxyglucose (18F-FDG) made from commercialized automated synthesis module is the most frequently used in tumor diagnoses. But the false positive findings, such as infectious tissues and post-operative surgical conditions, show strong uptake of 18F-FDG in PET scans which requires extra clinical procedures to confirm the results. Moreover, the false negative findings, such as low glycolytic activity tumors, reduce the accuracy of PET scans. Therefore, there will be new PET radiopharmaceuticals to redeem the defects of 18FDG-PET applications.
Current commercialized automated synthesis modules are suitable for clinical use, but researchers are difficult to modify these modules to synthesize their own radiopharmaceuticals. In this study, we developed a multi-purpose automated synthesis module for production of novel PET radiopharmaceuticals, such as gallium-68-ethylenedicysteine-glucosamine (68Ga-ECG), [18F]fluoropropyl-α-methyltyrosine (18F-FPAMT), and [18F]fluoro-5-propylhydroxy tryptophan (18F-FTP). The specifications of this module are the flexibility for editing synthesis recipes, the stable integration of its hardware and software, the rapid heating process, and the friendly user interface. The synthesis steps of nonradioactive standards for these three radiopharmaceuticals were developed, and the chemical structures and purities of nonradioactive references were confirmed. Then, the manual synthesis recipes of radiopharmaceuticals were followed the synthesis recipes of nonradioactive standards, and the yields and radiochemical purities of these radiopharmaceuticals were demonstrated in an acceptable range. Last, the manual synthesis recipes of these drugs were transformed to the automated synthesis recipes which can be practiced in this multi-purpose automated synthesis module.
The results showed this automated module is capable of synthesizing different radiopharmaceuticals. The pH value and radiochemical purity of automated synthesis are as good as the manual synthesis. Although the yields of automated syntheses are lower than the manual syntheses, the flexible functions of this module provide the opportunity for optimization of automated synthesis methods.
Keywords
Automated device, Radiochemistry, PET, Radiopharmaceuticals