Production of diverse PET probes with limited resources: 24 ¹⁸ F-labeled compounds prepared with a single radiosynthesizer

Abstract

New radiolabeled probes for positron-emission tomography (PET) are providing an ever-increasing ability to answer diverse research and clinical questions and to facilitate the discovery, development, and clinical use of drugs in patient care. Despite the high equipment and facility costs to produce PET probes, many radiopharmacies and radiochemistry laboratories use a dedicated radiosynthesizer to produce each probe, even if the equipment is idle much of the time, to avoid the challenges of reconfiguring the system fluidics to switch from one probe to another. To meet growing demand, more cost-efficient approaches are being developed, such as radiosynthesizers based on disposable "cassettes," that do not require reconfiguration to switch among probes. However, most cassette-based systems make sacrifices in synthesis complexity or tolerated reaction conditions, and some do not support custom programming, thereby limiting their generality. In contrast, the design of the ELIXYS FLEX/CHEM cassette-based synthesizer supports higher temperatures and pressures than other systems while also facilitating flexible synthesis development. In this paper, the syntheses of 24 known PET probes are adapted to this system to explore the possibility of using a single radiosynthesizer and hot cell for production of a diverse array of compounds with wide-ranging synthesis requirements, alongside synthesis development efforts. Most probes were produced with yields and synthesis times comparable to literature reports, and because hardware modification was unnecessary, it was convenient to frequently switch among probes based on demand. Although our facility supplies probes for preclinical imaging, the same workflow would be applicable in a clinical setting.

18F-FAC PET Selectively Images Liver-Infiltrating CD4 and CD8 T Cells in a Mouse Model of Autoimmune Hepatitis

“…18 F-FDG was from the UCLA Translational Imaging Division. 18 F-FAC and 18 F-DFA were synthesized as previously described (32). The mice were injected with tracer approximately 30 h after the ConA treatment and were imaged 1-3 d before and then again 2, 4, 8, and 12 wk after the adenovirus injections.…”

“…Here, we study 18 F-FDG, 18 F-FAC, and 18 F-DFA in mouse models of autoimmune and viral hepatitis. 18 F-DFA instead of 18 F-2-deoxy-2-fluororibose was chosen here because 18 F-DFA can be synthesized on an automated radiosynthesizer and its radiochemical precursor is commercially available (32). Our results suggest that PET imaging with radiotracers that measure ribose and deoxynucleoside salvage can be used to image and quantify hepatocyte inflammation and liver-infiltrating T lymphocytes during autoimmune hepatitis.…”

Fully automated peptide radiolabeling from [18F]fluoride

“…As a result, [ 18 F] FPy-TFP was produced with average yields of 76.1 AE 3.5% and sufficiently high radiochemical and chemical purities. These yields are comparable to other automated 18 32 Radiolabeling of peptides with [ 18 F]FPy-TFP were previously performed manually using a variety of peptide coupling conditions. 38,[44][45][46] The original manual peptide radiolabeling with [ 18 F]FPy-TFP by Olberg et al utilized a 1 : 1 : 1 DMSO : MeCN : phosphate buffer (pH-9.0), 3-5 mg of peptide, and a reaction temperature of 40 C for 15 minutes to generate the [ 18 F]FPy-peptide in a 22.5 AE 6.0% yield (total synthesis time ¼ 85 minutes).…”

“…4 Several automated syntheses of 18 35 The radiochemical yields for these automated productions are comparable, if not better than the analogous manual protocols. [32][33][34][35] Automated protocols capable of generating 18 Fpeptides from uorine-18 without manual interventions are less prevalent, as multiple purications are typically needed for both the intermediate 18 F-prosthetic and the nal 18 F-peptide radiotracer. 4,31 For example, Thonon et al, used the FASTLab™ GE synthesis module for the production of [ 18 F]SFB via both a one-and two-pot method, followed by coupling to an RGD peptide (PRGD2).…”

Tri-functional platform for construction of modular antibody fragments for in vivo18F-PET or NIRF molecular imaging

“…In vivo molecular imaging Synthesis of [ 18 F]uoroethoxy TCO was automated on the ELIXYS FLEX/CHEM radiochemical synthesizer (Soe Biosciences) as described previously. 28 For 18 F-labeling, reformulated [ 18 F]uoroethoxy TCO (37 MBq) was added to TFP-cDb (100 mg in 100 mL PBS, pH 7.4) and the mixture was incubated for 10 minutes at room temperature (Fig. 3A).…”