Katherine Liddell
Pronouns: she, her, hers
Research Mentor(s): Peter Scott
Co-Presenter:
Research Mentor School/College/Department: Nuclear Medicine/Radiology / Medicine
Presentation Date: April 20
Presentation Type: Oral5
Session: Session 6 – 4:40pm – 5:30 pm
Room: Breakout room 3
Authors:
Presenter: 1
Abstract
Positron-emission tomography (PET) is a molecular imagining technique in which patients are injected with a radiotracer (a bioactive molecule tagged with a positron-emitting radionuclide). The functional information that is then obtained from the PET scan can be used in a healthcare setting as part of a move towards personalized medicine, or to support drug discovery efforts. In this project, we synthesized 2-tert-butyl-4-chloro-5-(6-[2-(2[18F]fluroethoxy)-ethoxy]-2H-pyridazin-3-one ([18F]BCPP-EF) for quantitative imaging of mitochondrial complex 1 (MC-1) activity in vivo. Using the literature procedures, we were able to successfully synthesize the tosylate labeling precursor and unlabeled 19F-reference standard, confirmed by NMR and mass spectroscopy. Next, the radiosynthesis of [18F]BCPP-EF was optimized. As there are no reports of fully automated synthesis of this tracer, we started optimizing our automation runs. We began optimization of [18F] BCPP-EF by nucleophilic reaction of tosyl precursor with azeotropically dried [18F] in anhydrous acetonitrile at 80°C for 10 minutes which yielded in high molar activity, radiochemical purity, and in good radiochemical yields. To avoid the need for GC analysis during quality control testing, thus saving time, we developed a green synthesis using only class-3 solvents. To have an ecofriendly green method, we eliminated MeCN from the reaction and repeated [18F]-fluorination of the tosyl precursor in anhydrous DMSO at 80°C for 10 minutes, which resulted in good radiochemical yields (24.3%), molar activity (6521 ± 2843 Ci/mmol) and radiochemical purity of product (97.2%). Gratefully, [18F]BCPP-EF did not show any signs of radiolytic instability. 3 validation runs to qualify the radiosynthesis for clinical use were conducted and presented successful results. It is expected that use of this radiotracer in clinical PET will begin within 3-6 months. The PET imaging agent [18F]BCPP-EF is a promising candidate for imaging patients with neurogenerative diseases such as Parkinson’s to support disease management, track disease progression and evaluate experimental therapies.
Engineering, Interdisciplinary, Natural/Life Sciences
