Applying aryltrifluoroborates as PET imaging agents

This dissertation is focused on applying aryltrifluoroborates (ArBF₃s) as PET imaging agents. Several aspects of this new ¹⁸F-labeling technique are addressed. These include the hydrolytic stability of heteroaryltrifluoroborates (HetArBF₃s), the fluoridation of arylboronic acids/esters and the radiosyntheses of several ¹⁸F-ArBF₃ labeled biomolecules for potential PET imaging applications. The solvolysis of several N-HetArBF₃s under physiological conditions was studied with ¹⁹F NMR spectroscopy in Chapter 2. All the N-HetArBF₃s tested therein displayed excellent solvolytic stability under physiological conditions. It is expected that these HetArBF₃s can be further applied as ¹⁸F-labeled PET imaging agents. In Chapter 3, a rapid fluoridation was carried out under conditions with low fluoride concentrations in a short reaction time (~ one hour). Via TLC-fluorescent densitometry, ¹⁹F NMR spectroscopy, and radio-HPLC, the fluoridation of different arylboronic acids/esters was investigated. It was found that the fluoridation occurs relatively rapidly in the presence of 3 to 5 equivalents of fluoride in acidic aqueous CH₃CN at room temperature. Under such conditions, radiochemical yields of 20-30% can be achieved. It was also noticed that arylboronates with acid-sensitive protecting groups could undergo fluoridations rapidly comparable to the arylboronic acids. In Chapter 4, marimastat, an MMP inhibitor, was labeled with an ¹⁸F-ArBF₃ to image breast cancer in mice. An unoptimized isolated radiochemical yield of ~ 1.5% and specific activities of 0.179 and 0.396 Ci/µmol were obtained within two hours including packaging. The blocking experiment suggested that the tumor uptake of Mar-¹⁸F-ArBF₃ was MMP specific. This one-step aqueous fluoridation was also applied to label a urea-based PSMA inhibitor (Chapter 5) and RGD-containing cyclopeptides (Chapter 8). Radiochemical yields ranging from 10% to 25% were obtained within one hour and good HPLC separation was achieved. In addition, a one-pot two-step labeling strategy was developed in Chapter 6 to label acid-sensitive biomolecules with ¹⁸F-ArBF₃s. The copper(I) catalyzed 1,3-dipolar cycloaddition was successfully used to conjugate ¹⁸F-ArBF₃s with biomolecules including oligonucleotides (Chapter 6), folate (Chapter 7), and a cyclic RGD-peptide (Chapter 8) with radiochemical yields of 20-30% over two steps in one hour.Science, Faculty ofChemistry, Department ofGraduat