The Open Collections website will be undergoing maintenance on Wednesday December 7th from 9pm to 11pm PST. The site may be temporarily unavailable during this time.

UBC Theses and Dissertations

UBC Theses Logo

UBC Theses and Dissertations

Applying aryltrifluoroborates as PET imaging agents Li, Ying

Abstract

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.

Item Media

Item Citations and Data

Rights

Attribution-NonCommercial-NoDerivatives 4.0 International