Developing Versatile and Facile Chemical Synthesis Methodologies for Preparation of 18F-Tracers for PET Imaging

Project Summary/Abstract Positron emission tomography (PET) is an exquisitely sensitive and quantitative imaging modality with numerous applications in oncology, neuroimaging, infection/inflammation, and cardiology. PET has great potential for hybrid imaging techniques in which nuclear medicine can be combined with anatomic imaging techniques such as magnetic resonance imaging (MRI). Such approaches have changed the diagnostic algorithm in many fields including oncology while proving very cost-effective for clinical applications.Chemical properties (compared to other PET isotopes) and its relatively long half-life make 18F the most popular nuclei for PET imaging and almost half of all PET radiotracer molecules are based on 18F. The unusual chemistry of fluorinating agents of all types makes incorporation of 18F into the molecular precursors of the desired radiotracers very challenging.Dr. Daryaei, PI, has developed a novel, high efficiency and facile chemical synthesis process for the preparation and purification of 18F-radiotracers that is applicable to biologics. The methodology does not require chemistry experts; anyone with basic laboratory knowledge and skill can perform the process. In this proposed methodology, a cold derivative of the desired radiotracer molecules which contains 19F (normal isotope of fluorine) is prepared, purified, characterized, and stored. The desired 18F-containing radiotracer molecule is prepared, on demand, using a simple and highly efficient 19F/18F exchange process, wherein a non-radioactive 19F atom is replaced with the needed 18F atom, quickly and simply. Separation of unreacted 18F and 19F from the radiotracer is performed using a pre-packed C18 or C8 column (Sep-Pak), dialysis, or any other chromatography method in a very short period of time. The innovation is a platform technology which allows preparation of any type of radiotracers including 18F- bearing peptides, affibodies, scFvs, antibodies, DNA, RNA, small molecules, and MRI, fluorescence, and ultrasound contrast agents. The team have prepared, characterized, and tested 18F-labled peptides and PEGylated biomolecules using this technology. The fundamental aspects of the technology is the subject of a pending patent application (Method of synthesizing 18F radiolabeled biomolecular agents; WO 2018169942Al).The overall goal of this project is to further validate the technology for 18F-labeling of larger proteins and evaluate their biological activities in vitro and in vivo. We are going to expand our 18F-labeling chemical toolbox by employing more biologically common chemistries including NHS ester, maleimide, click chemistry, and diels-alder reactions to prepare the intermediates. We will use commercially available scFv and affibody versions of anti-HER2 antibody as our model system to test biomolecule adaptability of our technology. We will finally confirm detection of HER2 target by 18F-scFv or 18F-affibody using a PET/MRI scanner to show biological activities of the technology.Project Narrative (3 sentences) Positron emission tomography (PET) is an exquisitely sensitive and quantitative imaging modality with numerous applications in oncology, neuroimaging, infection/inflammation, and cardiology. Harsh reaction condition makes 18F-Labeling, as the most popular isotope for PET imaging, very challenging and difficult. We are developing (pending patent application) a facile and versatile chemistry methodology for non-chemists to perform 18F-labeling of biologics under physiological condition.